Skip to main content

Advertisement

SpringerLink
Log in

Functions of ‘A disintegrin and metalloproteases (ADAMs)’ in the mammalian nervous system

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

‘A disintegrin and metalloproteases’ (ADAMs) are a family of transmembrane proteins with diverse functions in multicellular organisms. About half of the ADAMs are active metalloproteases and cleave numerous cell surface proteins, including growth factors, receptors, cytokines and cell adhesion proteins. The other ADAMs have no catalytic activity and function as adhesion proteins or receptors. Some ADAMs are ubiquitously expressed, others are expressed tissue specifically. This review highlights functions of ADAMs in the mammalian nervous system, including their links to diseases. The non-proteolytic ADAM11, ADAM22 and ADAM23 have key functions in neural development, myelination and synaptic transmission and are linked to epilepsy. Among the proteolytic ADAMs, ADAM10 is the best characterized one due to its substrates Notch and amyloid precursor protein, where cleavage is required for nervous system development or linked to Alzheimer’s disease (AD), respectively. Recent work demonstrates that ADAM10 has additional substrates and functions in the nervous system and its substrate selectivity may be regulated by tetraspanins. New roles for other proteolytic ADAMs in the nervous system are also emerging. For example, ADAM8 and ADAM17 are involved in neuroinflammation. ADAM17 additionally regulates neurite outgrowth and myelination and its activity is controlled by iRhoms. ADAM19 and ADAM21 function in regenerative processes upon neuronal injury. Several ADAMs, including ADAM9, ADAM10, ADAM15 and ADAM30, are potential drug targets for AD. Taken together, this review summarizes recent progress concerning substrates and functions of ADAMs in the nervous system and their use as drug targets for neurological and psychiatric diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

The pictures were modified from https://smart.servier.com

Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

ADAM:

A disintegrin and metalloprotease

LGI:

Leucine-rich glioma-inactivated protein

PSD-95:

Postsynaptic density protein-95

CNS:

Central nervous system

PNS:

Peripheral nervous system

AMPA:

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

EGF:

Epidermal growth factor

SC:

Schwann cell

PrPc :

Cellular prion protein

PrPsc :

Pathological prion protein

ECM:

Extracellular matrix

APP:

Amyloid precursor protein

AD:

Alzheimer’s disease

NICD:

Notch intracellular domain

NCAM:

Neuronal cell adhesion molecule

Nrp1:

Neuropilin1

NrCAM:

Neural glial-related cell adhesion molecule

NLGN:

Neuroligin

NRXN:

Neurexin

OPCs:

Oligodendrocyte precursor cells

NG2:

Nerve–glia antigen 2

Aβ:

Amyloid β

TSPAN:

Tetraspanin

LRP-1:

Low density lipoprotein receptor-related protein 1

HB-EGF:

Heparin-binding epidermal growth factor-like growth factor

NRG1:

Neuregulin-1

TREM2:

Triggering receptor expressed in myeloid cells 2

TNFα:

Tumor necrosis factor α

TIMP:

Tissue inhibitor of metalloproteases

NPR:

Neuronal pentraxin receptor

KL1:

Kit ligand-1

References

  1. Lichtenthaler SF, Lemberg MK, Fluhrer R (2018) Proteolytic ectodomain shedding of membrane proteins in mammals-hardware, concepts, and recent developments. EMBO J 37(15):e99456. https://doi.org/10.15252/embj.201899456

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Cho C (2012) Testicular and epididymal ADAMs: expression and function during fertilization. Natre Rev Urol 9(10):550–560. https://doi.org/10.1038/nrurol.2012.167

    Article  CAS  Google Scholar 

  3. Weber S, Saftig P (2012) Ectodomain shedding and ADAMs in development. Development 139(20):3693–3709. https://doi.org/10.1242/dev.076398

    Article  CAS  PubMed  Google Scholar 

  4. Mullooly M, McGowan PM, Crown J, Duffy MJ (2016) The ADAMs family of proteases as targets for the treatment of cancer. Cancer Biol Ther 17(8):870–880. https://doi.org/10.1080/15384047.2016.1177684

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Stocker W, Grams F, Baumann U, Reinemer P, Gomis-Ruth FX, McKay DB, Bode W (1995) The metzincins—topological and sequential relations between the astacins, adamalysins, serralysins, and matrixins (collagenases) define a superfamily of zinc-peptidases. Protein Sci 4(5):823–840. https://doi.org/10.1002/pro.5560040502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Wolfsberg TG, White JM (1996) ADAMs in fertilization and development. Dev Biol 180(2):389–401. https://doi.org/10.1006/dbio.1996.0313

    Article  CAS  PubMed  Google Scholar 

  7. Stone AL, Kroeger M, Sang QX (1999) Structure–function analysis of the ADAM family of disintegrin-like and metalloproteinase-containing proteins (review). J Protein Chem 18(4):447–465

    Article  CAS  Google Scholar 

  8. Schlomann U, Wildeboer D, Webster A, Antropova O, Zeuschner D, Knight CG, Docherty AJ, Lambert M, Skelton L, Jockusch H, Bartsch JW (2002) The metalloprotease disintegrin ADAM8. Processing by autocatalysis is required for proteolytic activity and cell adhesion. J Biol Chem 277(50):48210–48219. https://doi.org/10.1074/jbc.M203355200

    Article  CAS  PubMed  Google Scholar 

  9. Schlondorff J, Becherer JD, Blobel CP (2000) Intracellular maturation and localization of the tumour necrosis factor alpha convertase (TACE). Biochem J 347(Pt 1):131–138

    Article  CAS  Google Scholar 

  10. Brummer T, Pigoni M, Rossello A, Wang H, Noy PJ, Tomlinson MG, Blobel CP, Lichtenthaler SF (2018) The metalloprotease ADAM10 (a disintegrin and metalloprotease 10) undergoes rapid, postlysis autocatalytic degradation. FASEB J 32(7):3560–3573. https://doi.org/10.1096/fj.201700823RR

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Seals DF, Courtneidge SA (2003) The ADAMs family of metalloproteases: multidomain proteins with multiple functions. Genes Dev 17(1):7–30. https://doi.org/10.1101/gad.1039703

    Article  CAS  PubMed  Google Scholar 

  12. Giebeler N, Zigrino P (2016) A disintegrin and metalloprotease (ADAM): historical overview of their functions. Toxins (Basel) 8(4):122. https://doi.org/10.3390/toxins8040122

    Article  CAS  Google Scholar 

  13. Klein T, Bischoff R (2011) Active metalloproteases of the A Disintegrin and Metalloprotease (ADAM) family: biological function and structure. J Proteome Res 10(1):17–33. https://doi.org/10.1021/pr100556z

    Article  CAS  PubMed  Google Scholar 

  14. Edwards DR, Handsley MM, Pennington CJ (2008) The ADAM metalloproteinases. Mol Aspects Med 29(5):258–289. https://doi.org/10.1016/j.mam.2008.08.001

    Article  CAS  PubMed  Google Scholar 

  15. Sagane K, Yamazaki K, Mizui Y, Tanaka I (1999) Cloning and chromosomal mapping of mouse ADAM11, ADAM22 and ADAM23. Gene 236(1):79–86

    Article  CAS  Google Scholar 

  16. Kegel L, Aunin E, Meijer D, Bermingham JR (2013) LGI proteins in the nervous system. ASN Neuro 5(3):167–181. https://doi.org/10.1042/AN20120095

    Article  CAS  PubMed  Google Scholar 

  17. Rybnikova E, Karkkainen I, Pelto-Huikko M, Huovila AP (2002) Developmental regulation and neuronal expression of the cellular disintegrin ADAM11 gene in mouse nervous system. Neuroscience 112(4):921–934

    Article  CAS  Google Scholar 

  18. Kole MJ, Qian J, Waase MP, Klassen TL, Chen TT, Augustine GJ, Noebels JL (2015) Selective loss of presynaptic potassium channel clusters at the cerebellar basket cell terminal pinceau in Adam11 mutants reveals their role in ephaptic control of Purkinje cell firing. J Neurosci 35(32):11433–11444. https://doi.org/10.1523/JNEUROSCI.1346-15.2015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Blot A, Barbour B (2014) Ultra-rapid axon-axon ephaptic inhibition of cerebellar Purkinje cells by the pinceau. Nat Neurosci 17(2):289–295. https://doi.org/10.1038/nn.3624

    Article  CAS  PubMed  Google Scholar 

  20. Xie G, Harrison J, Clapcote SJ, Huang Y, Zhang JY, Wang LY, Roder JC (2010) A new Kv1.2 channelopathy underlying cerebellar ataxia. J Biol Chem 285(42):32160–32173. https://doi.org/10.1074/jbc.M110.153676

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Zhou L, Zhang CL, Messing A, Chiu SY (1998) Temperature-sensitive neuromuscular transmission in Kv1.1 null mice: role of potassium channels under the myelin sheath in young nerves. J Neurosci 18(18):7200–7215

    Article  CAS  Google Scholar 

  22. Takahashi E, Sagane K, Nagasu T, Kuromitsu J (2006) Altered nociceptive response in ADAM11-deficient mice. Brain Res 1097(1):39–42. https://doi.org/10.1016/j.brainres.2006.04.043

    Article  CAS  PubMed  Google Scholar 

  23. Takahashi E, Sagane K, Oki T, Yamazaki K, Nagasu T, Kuromitsu J (2006) Deficits in spatial learning and motor coordination in ADAM11-deficient mice. BMC Neurosci 7:19. https://doi.org/10.1186/1471-2202-7-19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Chen N, Koopmans F, Gordon A, Paliukhovich I, Klaassen RV, van der Schors RC, Peles E, Verhage M, Smit AB (1854) Li KW (2015) Interaction proteomics of canonical Caspr2 (CNTNAP2) reveals the presence of two Caspr2 isoforms with overlapping interactomes. Biochim Biophys Acta 7:827–833. https://doi.org/10.1016/j.bbapap.2015.02.008

    Article  CAS  Google Scholar 

  25. Sagane K, Ishihama Y, Sugimoto H (2008) LGI1 and LGI4 bind to ADAM22, ADAM23 and ADAM11. Int J Biol Sci 4(6):387–396

    Article  CAS  Google Scholar 

  26. Wang L, Hoggard JA, Korleski ED, Long GV, Ree BC, Hensley K, Bond SR, Wolfsberg TG, Chen J, Zeczycki TN, Bridges LC (2018) Multiple non-catalytic ADAMs are novel integrin alpha4 ligands. Mol Cell Biochem 442(1–2):29–38. https://doi.org/10.1007/s11010-017-3190-y

    Article  CAS  PubMed  Google Scholar 

  27. Sagane K, Ohya Y, Hasegawa Y, Tanaka I (1998) Metalloproteinase-like, disintegrin-like, cysteine-rich proteins MDC2 and MDC3: novel human cellular disintegrins highly expressed in the brain. Biochem J 334(Pt 1):93–98

    Article  CAS  Google Scholar 

  28. Sagane K, Hayakawa K, Kai J, Hirohashi T, Takahashi E, Miyamoto N, Ino M, Oki T, Yamazaki K, Nagasu T (2005) Ataxia and peripheral nerve hypomyelination in ADAM22-deficient mice. BMC Neurosci 6:33. https://doi.org/10.1186/1471-2202-6-33

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Zheng S, Gray EE, Chawla G, Porse BT, O’Dell TJ, Black DL (2012) PSD-95 is post-transcriptionally repressed during early neural development by PTBP1 and PTBP2. Nat Neurosci 15(3):381–388, s381. https://doi.org/10.1038/nn.3026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Fukata Y, Adesnik H, Iwanaga T, Bredt DS, Nicoll RA, Fukata M (2006) Epilepsy-related ligand/receptor complex LGI1 and ADAM22 regulate synaptic transmission. Science (New York, NY) 313(5794):1792–1795. https://doi.org/10.1126/science.1129947

    Article  CAS  Google Scholar 

  31. Lovero KL, Fukata Y, Granger AJ, Fukata M, Nicoll RA (2015) The LGI1-ADAM22 protein complex directs synapse maturation through regulation of PSD-95 function. Proc Natl Acad Sci USA 112(30):E4129–4137. https://doi.org/10.1073/pnas.1511910112

    Article  CAS  PubMed  Google Scholar 

  32. Fukata Y, Lovero KL, Iwanaga T, Watanabe A, Yokoi N, Tabuchi K, Shigemoto R, Nicoll RA, Fukata M (2010) Disruption of LGI1-linked synaptic complex causes abnormal synaptic transmission and epilepsy. Proc Natl Acad Sci USA 107(8):3799–3804. https://doi.org/10.1073/pnas.0914537107

    Article  PubMed  Google Scholar 

  33. Dazzo E, Leonardi E, Belluzzi E, Malacrida S, Vitiello L, Greggio E, Tosatto SC, Nobile C (2016) Secretion-positive LGI1 mutations linked to lateral temporal epilepsy impair binding to ADAM22 and ADAM23 receptors. PLoS Genet 12(10):e1006376. https://doi.org/10.1371/journal.pgen.1006376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Yokoi N, Fukata Y, Kase D, Miyazaki T, Jaegle M, Ohkawa T, Takahashi N, Iwanari H, Mochizuki Y, Hamakubo T, Imoto K, Meijer D, Watanabe M, Fukata M (2015) Chemical corrector treatment ameliorates increased seizure susceptibility in a mouse model of familial epilepsy. Nat Med 21(1):19–26. https://doi.org/10.1038/nm.3759

    Article  CAS  PubMed  Google Scholar 

  35. Fukata Y, Yokoi N, Miyazaki Y, Fukata M (2017) The LGI1-ADAM22 protein complex in synaptic transmission and synaptic disorders. Neurosci Res 116:39–45. https://doi.org/10.1016/j.neures.2016.09.011

    Article  CAS  PubMed  Google Scholar 

  36. Kegel L, Jaegle M, Driegen S, Aunin E, Leslie K, Fukata Y, Watanabe M, Fukata M, Meijer D (2014) Functional phylogenetic analysis of LGI proteins identifies an interaction motif crucial for myelination. Development 141(8):1749–1756. https://doi.org/10.1242/dev.107995

    Article  CAS  PubMed  Google Scholar 

  37. Muona M, Fukata Y, Anttonen AK, Laari A, Palotie A, Pihko H, Lonnqvist T, Valanne L, Somer M, Fukata M, Lehesjoki AE (2016) Dysfunctional ADAM22 implicated in progressive encephalopathy with cortical atrophy and epilepsy. Neurol Genet 2(1):e46. https://doi.org/10.1212/NXG.0000000000000046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Turetsky D, Garringer E, Patneau DK (2005) Stargazin modulates native AMPA receptor functional properties by two distinct mechanisms. J Neurosci 25(32):7438–7448. https://doi.org/10.1523/jneurosci.1108-05.2005

    Article  CAS  PubMed  Google Scholar 

  39. Noebels JL, Qiao X, Bronson RT, Spencer C, Davisson MT (1990) Stargazer: a new neurological mutant on chromosome 15 in the mouse with prolonged cortical seizures. Epilepsy Res 7(2):129–135

    Article  CAS  Google Scholar 

  40. Nicoll RA, Tomita S, Bredt DS (2006) Auxiliary subunits assist AMPA-type glutamate receptors. Science (New York, NY) 311(5765):1253–1256. https://doi.org/10.1126/science.1123339

    Article  CAS  Google Scholar 

  41. Lai M, Huijbers MG, Lancaster E, Graus F, Bataller L, Balice-Gordon R, Cowell JK, Dalmau J (2010) Investigation of LGI1 as the antigen in limbic encephalitis previously attributed to potassium channels: a case series. Lancet Neurol 9(8):776–785. https://doi.org/10.1016/s1474-4422(10)70137-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Irani SR, Alexander S, Waters P, Kleopa KA, Pettingill P, Zuliani L, Peles E, Buckley C, Lang B, Vincent A (2010) Antibodies to Kv1 potassium channel-complex proteins leucine-rich, glioma inactivated 1 protein and contactin-associated protein-2 in limbic encephalitis, Morvan’s syndrome and acquired neuromyotonia. Brain 133(9):2734–2748. https://doi.org/10.1093/brain/awq213

    Article  PubMed  PubMed Central  Google Scholar 

  43. Ohkawa T, Fukata Y, Yamasaki M, Miyazaki T, Yokoi N, Takashima H, Watanabe M, Watanabe O, Fukata M (2013) Autoantibodies to epilepsy-related LGI1 in limbic encephalitis neutralize LGI1–ADAM22 interaction and reduce synaptic AMPA receptors. J Neurosci 33(46):18161–18174. https://doi.org/10.1523/jneurosci.3506-13.2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Ogawa Y, Oses-Prieto J, Kim MY, Horresh I, Peles E, Burlingame AL, Trimmer JS, Meijer D, Rasband MN (2010) ADAM22, a Kv1 channel-interacting protein, recruits membrane-associated guanylate kinases to juxtaparanodes of myelinated axons. J Neurosci 30(3):1038–1048. https://doi.org/10.1523/jneurosci.4661-09.2010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Schulte U, Thumfart JO, Klocker N, Sailer CA, Bildl W, Biniossek M, Dehn D, Deller T, Eble S, Abbass K, Wangler T, Knaus HG, Fakler B (2006) The epilepsy-linked Lgi1 protein assembles into presynaptic Kv1 channels and inhibits inactivation by Kvbeta1. Neuron 49(5):697–706. https://doi.org/10.1016/j.neuron.2006.01.033

    Article  CAS  PubMed  Google Scholar 

  46. Boillot M, Huneau C, Marsan E, Lehongre K, Navarro V, Ishida S, Dufresnois B, Ozkaynak E, Garrigue J, Miles R, Martin B, Leguern E, Anderson MP, Baulac S (2014) Glutamatergic neuron-targeted loss of LGI1 epilepsy gene results in seizures. Brain 137(Pt 11):2984–2996. https://doi.org/10.1093/brain/awu259

    Article  PubMed  PubMed Central  Google Scholar 

  47. Mitchell KJ, Pinson KI, Kelly OG, Brennan J, Zupicich J, Scherz P, Leighton PA, Goodrich LV, Lu X, Avery BJ, Tate P, Dill K, Pangilinan E, Wakenight P, Tessier-Lavigne M, Skarnes WC (2001) Functional analysis of secreted and transmembrane proteins critical to mouse development. Nat Genet 28(3):241–249. https://doi.org/10.1038/90074

    Article  CAS  PubMed  Google Scholar 

  48. Owuor K, Harel NY, Englot DJ, Hisama F, Blumenfeld H, Strittmatter SM (2009) LGI1-associated epilepsy through altered ADAM23-dependent neuronal morphology. Mol Cell Neurosci 42(4):448–457. https://doi.org/10.1016/j.mcn.2009.09.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Yamagata A, Miyazaki Y, Yokoi N, Shigematsu H, Sato Y, Goto-Ito S, Maeda A, Goto T, Sanbo M, Hirabayashi M, Shirouzu M, Fukata Y, Fukata M, Fukai S (2018) Structural basis of epilepsy-related ligand-receptor complex LGI1-ADAM22. Nat Commun 9(1):1546. https://doi.org/10.1038/s41467-018-03947-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Leonardi E, Andreazza S, Vanin S, Busolin G, Nobile C, Tosatto SC (2011) A computational model of the LGI1 protein suggests a common binding site for ADAM proteins. PLoS One 6(3):e18142. https://doi.org/10.1371/journal.pone.0018142

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Liu H, Shim AH, He X (2009) Structural characterization of the ectodomain of a disintegrin and metalloproteinase-22 (ADAM22), a neural adhesion receptor instead of metalloproteinase: insights on ADAM function. J Biol Chem 284(42):29077–29086. https://doi.org/10.1074/jbc.M109.014258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Seegar TCM, Killingsworth LB, Saha N, Meyer PA, Patra D, Zimmerman B, Janes PW, Rubinstein E, Nikolov DB, Skiniotis G, Kruse AC, Blacklow SC (2017) Structural basis for regulated proteolysis by the alpha-secretase ADAM10. Cell 171(7):1638–1648.e1637. https://doi.org/10.1016/j.cell.2017.11.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Ozkaynak E, Abello G, Jaegle M, van Berge L, Hamer D, Kegel L, Driegen S, Sagane K, Bermingham JR Jr, Meijer D (2010) Adam22 is a major neuronal receptor for Lgi4-mediated Schwann cell signaling. J Neurosci 30(10):3857–3864. https://doi.org/10.1523/JNEUROSCI.6287-09.2010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Xue S, Maluenda J, Marguet F, Shboul M, Quevarec L, Bonnard C, Ng AY, Tohari S, Tan TT, Kong MK, Monaghan KG, Cho MT, Siskind CE, Sampson JB, Rocha CT, Alkazaleh F, Gonzales M, Rigonnot L, Whalen S, Gut M, Gut I, Bucourt M, Venkatesh B, Laquerriere A, Reversade B, Melki J (2017) Loss-of-function mutations in LGI4, a secreted ligand involved in Schwann cell myelination, are responsible for arthrogryposis multiplex congenita. Am J Hum Genet 100(4):659–665. https://doi.org/10.1016/j.ajhg.2017.02.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Nishino J, Saunders TL, Sagane K, Morrison SJ (2010) Lgi4 promotes the proliferation and differentiation of glial lineage cells throughout the developing peripheral nervous system. J Neurosci 30(45):15228–15240. https://doi.org/10.1523/JNEUROSCI.2286-10.2010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Godde NJ, D’Abaco GM, Paradiso L, Novak U (2006) Efficient ADAM22 surface expression is mediated by phosphorylation-dependent interaction with 14-3-3 protein family members. J Cell Sci 119(Pt 16):3296–3305. https://doi.org/10.1242/jcs.03065

    Article  CAS  PubMed  Google Scholar 

  57. Grieve AG, Xu H, Kunzel U, Bambrough P, Sieber B, Freeman M (2017) Phosphorylation of iRhom2 at the plasma membrane controls mammalian TACE-dependent inflammatory and growth factor signalling. Elife 6:e23968. https://doi.org/10.7554/eLife.23968

    Article  PubMed  PubMed Central  Google Scholar 

  58. Goldsmith AP, Gossage SJ, ffrench-Constant C (2004) ADAM23 is a cell-surface glycoprotein expressed by central nervous system neurons. J Neurosci Res 78(5):647–658. https://doi.org/10.1002/jnr.20320

    Article  CAS  PubMed  Google Scholar 

  59. Koskinen LL, Seppala EH, Weissl J, Jokinen TS, Viitmaa R, Hanninen RL, Quignon P, Fischer A, Andre C, Lohi H (2017) ADAM23 is a common risk gene for canine idiopathic epilepsy. BMC Genet 18(1):8. https://doi.org/10.1186/s12863-017-0478-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Markus-Koch A, Schmitt O, Seemann S, Lukas J, Koczan D, Ernst M, Fuellen G, Wree A, Rolfs A, Luo J (2017) ADAM23 promotes neuronal differentiation of human neural progenitor cells. Cell Mol Biol Lett 22:16. https://doi.org/10.1186/s11658-017-0045-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Costa MD, Paludo KS, Klassen G, Lopes MH, Mercadante AF, Martins VR, Camargo AA, Nakao LS, Zanata SM (2009) Characterization of a specific interaction between ADAM23 and cellular prion protein. Neurosci Lett 461(1):16–20. https://doi.org/10.1016/j.neulet.2009.05.049

    Article  CAS  PubMed  Google Scholar 

  62. Cal S, Freije JM, Lopez JM, Takada Y, Lopez-Otin C (2000) ADAM 23/MDC3, a human disintegrin that promotes cell adhesion via interaction with the alphavbeta3 integrin through an RGD-independent mechanism. Mol Biol Cell 11(4):1457–1469. https://doi.org/10.1091/mbc.11.4.1457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Elizondo DM, Andargie TE, Marshall KM, Zariwala AM, Lipscomb MW (2016) Dendritic cell expression of ADAM23 governs T cell proliferation and cytokine production through the alpha(v)beta(3) integrin receptor. J Leukoc Biol 100(5):855–864. https://doi.org/10.1189/jlb.2HI1115-525R

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Calmon MF, Colombo J, Carvalho F, Souza FP, Filho JF, Fukuyama EE, Camargo AA, Caballero OL, Tajara EH, Cordeiro JA, Rahal P (2007) Methylation profile of genes CDKN2A (p14 and p16), DAPK1, CDH1, and ADAM23 in head and neck cancer. Cancer Genet Cytogenet 173(1):31–37. https://doi.org/10.1016/j.cancergencyto.2006.09.008

    Article  CAS  PubMed  Google Scholar 

  65. Kwon NS, Kim DS, Yun HY (2017) Leucine-rich glioma inactivated 3: integrative analyses support its prognostic role in glioma. OncoTargets Ther 10:2721–2728. https://doi.org/10.2147/ott.s138912

    Article  CAS  Google Scholar 

  66. Verbisck NV, Costa ET, Costa FF, Cavalher FP, Costa MD, Muras A, Paixao VA, Moura R, Granato MF, Ierardi DF, Machado T, Melo F, Ribeiro KB, Cunha IW, Lima VC, Maciel Mdo S, Carvalho AL, Soares FF, Zanata S, Sogayar MC, Chammas R, Camargo AA (2009) ADAM23 negatively modulates alpha(v)beta(3) integrin activation during metastasis. Cancer Res 69(13):5546–5552. https://doi.org/10.1158/0008-5472.can-08-2976

    Article  CAS  PubMed  Google Scholar 

  67. Dkhil MA, Bauomy AA, Diab MS, Wahab R, Delic D, Al-Quraishy S (2015) Impact of gold nanoparticles on brain of mice infected with Schistosoma mansoni. Parasitol Res 114(10):3711–3719. https://doi.org/10.1007/s00436-015-4600-2

    Article  PubMed  Google Scholar 

  68. Mubaraki MA, Hafiz TA, Al-Quraishy S, Dkhil MA (2017) Oxidative stress and genes regulation of cerebral malaria upon Zizyphus spina-christi treatment in a murine model. Microb Pathog 107:69–74. https://doi.org/10.1016/j.micpath.2017.03.017

    Article  PubMed  Google Scholar 

  69. Yoshida S, Setoguchi M, Higuchi Y, Akizuki S, Yamamoto S (1990) Molecular cloning of cDNA encoding MS2 antigen, a novel cell surface antigen strongly expressed in murine monocytic lineage. Int Immunol 2(6):585–591

    Article  CAS  Google Scholar 

  70. Yoshiyama K, Higuchi Y, Kataoka M, Matsuura K, Yamamoto S (1997) CD156 (human ADAM8): expression, primary amino acid sequence, and gene location. Genomics 41(1):56–62. https://doi.org/10.1006/geno.1997.4607

    Article  CAS  PubMed  Google Scholar 

  71. Kelly K, Hutchinson G, Nebenius-Oosthuizen D, Smith AJ, Bartsch JW, Horiuchi K, Rittger A, Manova K, Docherty AJ, Blobel CP (2005) Metalloprotease–disintegrin ADAM8: expression analysis and targeted deletion in mice. Dev Dyn 232(1):221–231. https://doi.org/10.1002/dvdy.20221

    Article  CAS  PubMed  Google Scholar 

  72. Koller G, Schlomann U, Golfi P, Ferdous T, Naus S, Bartsch JW (2009) ADAM8/MS2/CD156, an emerging drug target in the treatment of inflammatory and invasive pathologies. Curr Pharm Des 15(20):2272–2281

    Article  CAS  Google Scholar 

  73. Schlomann U, Rathke-Hartlieb S, Yamamoto S, Jockusch H, Bartsch JW (2000) Tumor necrosis factor alpha induces a metalloprotease–disintegrin, ADAM8 (CD 156): implications for neuron-glia interactions during neurodegeneration. J Neurosci 20(21):7964–7971

    Article  CAS  Google Scholar 

  74. Bartsch JW, Wildeboer D, Koller G, Naus S, Rittger A, Moss ML, Minai Y, Jockusch H (2010) Tumor necrosis factor-alpha (TNF-alpha) regulates shedding of TNF-alpha receptor 1 by the metalloprotease–disintegrin ADAM8: evidence for a protease-regulated feedback loop in neuroprotection. J Neurosci 30(36):12210–12218. https://doi.org/10.1523/JNEUROSCI.1520-10.2010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Liang J, Wang W, Sorensen D, Medina S, Ilchenko S, Kiselar J, Surewicz WK, Booth SA, Kong Q (2012) Cellular prion protein regulates its own alpha-cleavage through ADAM8 in skeletal muscle. J Biol Chem 287(20):16510–16520. https://doi.org/10.1074/jbc.M112.360891

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Mahoney ET, Benton RL, Maddie MA, Whittemore SR, Hagg T (2009) ADAM8 is selectively up-regulated in endothelial cells and is associated with angiogenesis after spinal cord injury in adult mice. J Comp Neurol 512(2):243–255. https://doi.org/10.1002/cne.21902

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Shin HY, Kim H, Kwon MJ, Hwang DH, Lee K, Kim BG (2014) Molecular and cellular changes in the lumbar spinal cord following thoracic injury: regulation by treadmill locomotor training. PLoS One 9(2):e88215. https://doi.org/10.1371/journal.pone.0088215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Naus S, Reipschläger S, Wildeboer D, Lichtenthaler SF, Mitterreiter S, Guan Z, Moss ML, Bartsch JW (2006) Identification of candidate substrates for ectodomain shedding by the metalloprotease-disintegrin ADAM8. Biol Chem 387(3):337–346

  79. Naus S, Richter M, Wildeboer D, Moss M, Schachner M, Bartsch JW (2004) Ectodomain shedding of the neural recognition molecule CHL1 by the metalloprotease–disintegrin ADAM8 promotes neurite outgrowth and suppresses neuronal cell death. J Biol Chem 279(16):16083–16090. https://doi.org/10.1074/jbc.M400560200

    Article  CAS  PubMed  Google Scholar 

  80. Zack MD, Malfait AM, Skepner AP, Yates MP, Griggs DW, Hall T, Hills RL, Alston JT, Nemirovskiy OV, Radabaugh MR, Leone JW, Arner EC, Tortorella MD (2009) ADAM-8 isolated from human osteoarthritic chondrocytes cleaves fibronectin at Ala(271). Arthritis Rheum 60(9):2704–2713. https://doi.org/10.1002/art.24753

    Article  CAS  PubMed  Google Scholar 

  81. Horiuchi K, Weskamp G, Lum L, Hammes HP, Cai H, Brodie TA, Ludwig T, Chiusaroli R, Baron R, Preissner KT, Manova K, Blobel CP (2003) Potential role for ADAM15 in pathological neovascularization in mice. Mol Cell Biol 23(16):5614–5624

    Article  CAS  Google Scholar 

  82. Weskamp G, Cai H, Brodie TA, Higashyama S, Manova K, Ludwig T, Blobel CP (2002) Mice lacking the metalloprotease–disintegrin MDC9 (ADAM9) have no evident major abnormalities during development or adult life. Mol Cell Biol 22(5):1537–1544

    Article  CAS  Google Scholar 

  83. Sahin U, Weskamp G, Kelly K, Zhou HM, Higashiyama S, Peschon J, Hartmann D, Saftig P, Blobel CP (2004) Distinct roles for ADAM10 and ADAM17 in ectodomain shedding of six EGFR ligands. J Cell Biol 164(5):769–779. https://doi.org/10.1083/jcb.200307137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Ortiz RM, Karkkainen I, Huovila AP, Honkaniemi J (2005) ADAM9, ADAM10, and ADAM15 mRNA levels in the rat brain after kainic acid-induced status epilepticus. Brain Res Mol Brain Res 137(1–2):272–275. https://doi.org/10.1016/j.molbrainres.2005.03.008

    Article  CAS  PubMed  Google Scholar 

  85. Rybnikova E, Gluschenko T, Galeeva A, Tulkova E, Nalivaeva NN, Makova NZ, Turner AJ, Samoilov M (2012) Differential expression of ADAM15 and ADAM17 metalloproteases in the rat brain after severe hypobaric hypoxia and hypoxic preconditioning. Neurosci Res 72(4):364–373. https://doi.org/10.1016/j.neures.2011.12.010

    Article  CAS  PubMed  Google Scholar 

  86. Bosse F, Petzold G, Greiner-Petter R, Pippirs U, Gillen C, Muller HW (2000) Cellular localization of the disintegrin CRII-7/rMDC15 mRNA in rat PNS and CNS and regulated expression in postnatal development and after nerve injury. Glia 32(3):313–327

    Article  CAS  Google Scholar 

  87. Dreymueller D, Uhlig S, Ludwig A (2015) ADAM-family metalloproteinases in lung inflammation: potential therapeutic targets. Am J Physiol Lung Cell Mol Physiol 308(4):L325–343. https://doi.org/10.1152/ajplung.00294.2014

    Article  CAS  PubMed  Google Scholar 

  88. Marzia M, Guaiquil V, Horne WC, Blobel CP, Baron R, Chiusaroli R (2011) Lack of ADAM15 in mice is associated with increased osteoblast function and bone mass. Biol Chem 392(10):877–885. https://doi.org/10.1515/BC.2011.080

    Article  CAS  PubMed  Google Scholar 

  89. Parry DA, Toomes C, Bida L, Danciger M, Towns KV, McKibbin M, Jacobson SG, Logan CV, Ali M, Bond J, Chance R, Swendeman S, Daniele LL, Springell K, Adams M, Johnson CA, Booth AP, Jafri H, Rashid Y, Banin E, Strom TM, Farber DB, Sharon D, Blobel CP, Pugh EN Jr, Pierce EA, Inglehearn CF (2009) Loss of the metalloprotease ADAM9 leads to cone-rod dystrophy in humans and retinal degeneration in mice. Am J Hum Genet 84(5):683–691. https://doi.org/10.1016/j.ajhg.2009.04.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Koike H, Tomioka S, Sorimachi H, Saido TC, Maruyama K, Okuyama A, Fujisawa-Sehara A, Ohno S, Suzuki K, Ishiura S (1999) Membrane-anchored metalloprotease MDC9 has an alpha-secretase activity responsible for processing the amyloid precursor protein. Biochem J 343(Pt 2):371–375

    Article  CAS  Google Scholar 

  91. Kuhn PH, Wang H, Dislich B, Colombo A, Zeitschel U, Ellwart JW, Kremmer E, Rossner S, Lichtenthaler SF (2010) ADAM10 is the physiologically relevant, constitutive alpha-secretase of the amyloid precursor protein in primary neurons. EMBO J 29(17):3020–3032. https://doi.org/10.1038/emboj.2010.167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Jorissen E, Prox J, Bernreuther C, Weber S, Schwanbeck R, Serneels L, Snellinx A, Craessaerts K, Thathiah A, Tesseur I, Bartsch U, Weskamp G, Blobel CP, Glatzel M, De Strooper B, Saftig P (2010) The disintegrin/metalloproteinase ADAM10 is essential for the establishment of the brain cortex. J Neurosci 30(14):4833–4844. https://doi.org/10.1523/JNEUROSCI.5221-09.2010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Colombo A, Wang H, Kuhn PH, Page R, Kremmer E, Dempsey PJ, Crawford HC, Lichtenthaler SF (2013) Constitutive alpha- and beta-secretase cleavages of the amyloid precursor protein are partially coupled in neurons, but not in frequently used cell lines. Neurobiol Dis 49:137–147. https://doi.org/10.1016/j.nbd.2012.08.011

    Article  CAS  PubMed  Google Scholar 

  94. Amour A, Knight CG, English WR, Webster A, Slocombe PM, Knauper V, Docherty AJ, Becherer JD, Blobel CP, Murphy G (2002) The enzymatic activity of ADAM8 and ADAM9 is not regulated by TIMPs. FEBS Lett 524(1–3):154–158

    Article  CAS  Google Scholar 

  95. Cong L, Jia J (2011) Promoter polymorphisms which regulate ADAM9 transcription are protective against sporadic Alzheimer’s disease. Neurobiol Aging 32(1):54–62. https://doi.org/10.1016/j.neurobiolaging.2009.01.001

    Article  CAS  PubMed  Google Scholar 

  96. Guaiquil V, Swendeman S, Yoshida T, Chavala S, Campochiaro PA, Blobel CP (2009) ADAM9 is involved in pathological retinal neovascularization. Mol Cell Biol 29(10):2694–2703. https://doi.org/10.1128/mcb.01460-08

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Sung SY, Kubo H, Shigemura K, Arnold RS, Logani S, Wang R, Konaka H, Nakagawa M, Mousses S, Amin M, Anderson C, Johnstone P, Petros JA, Marshall FF, Zhau HE, Chung LW (2006) Oxidative stress induces ADAM9 protein expression in human prostate cancer cells. Cancer Res 66(19):9519–9526. https://doi.org/10.1158/0008-5472.Can-05-4375

    Article  CAS  PubMed  Google Scholar 

  98. Tousseyn T, Thathiah A, Jorissen E, Raemaekers T, Konietzko U, Reiss K, Maes E, Snellinx A, Serneels L, Nyabi O, Annaert W, Saftig P, Hartmann D, De Strooper B (2009) ADAM10, the rate-limiting protease of regulated intramembrane proteolysis of Notch and other proteins, is processed by ADAMS-9, ADAMS-15, and the gamma-secretase. J Biol Chem 284(17):11738–11747. https://doi.org/10.1074/jbc.M805894200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Moss ML, Powell G, Miller MA, Edwards L, Qi B, Sang QX, De Strooper B, Tesseur I, Lichtenthaler SF, Taverna M, Zhong JL, Dingwall C, Ferdous T, Schlomann U, Zhou P, Griffith LG, Lauffenburger DA, Petrovich R, Bartsch JW (2011) ADAM9 inhibition increases membrane activity of ADAM10 and controls alpha-secretase processing of amyloid precursor protein. J Biol Chem 286(47):40443–40451. https://doi.org/10.1074/jbc.M111.280495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Cisse MA, Sunyach C, Lefranc-Jullien S, Postina R, Vincent B, Checler F (2005) The disintegrin ADAM9 indirectly contributes to the physiological processing of cellular prion by modulating ADAM10 activity. J Biol Chem 280(49):40624–40631. https://doi.org/10.1074/jbc.M506069200

    Article  CAS  PubMed  Google Scholar 

  101. Sharma K, Schmitt S, Bergner CG, Tyanova S, Kannaiyan N, Manrique-Hoyos N, Kongi K, Cantuti L, Hanisch UK, Philips MA, Rossner MJ, Mann M, Simons M (2015) Cell type- and brain region-resolved mouse brain proteome. Nat Neurosci 18(12):1819–1831. https://doi.org/10.1038/nn.4160

    Article  CAS  PubMed  Google Scholar 

  102. Karkkainen I, Rybnikova E, Pelto-Huikko M, Huovila AP (2000) Metalloprotease–disintegrin (ADAM) genes are widely and differentially expressed in the adult CNS. Mol Cell Neurosci 15(6):547–560. https://doi.org/10.1006/mcne.2000.0848

    Article  CAS  PubMed  Google Scholar 

  103. Kuhn PH, Colombo AV, Schusser B, Dreymueller D, Wetzel S, Schepers U, Herber J, Ludwig A, Kremmer E, Montag D, Muller U, Schweizer M, Saftig P, Brase S, Lichtenthaler SF (2016) Systematic substrate identification indicates a central role for the metalloprotease ADAM10 in axon targeting and synapse function. Elife 5:e12748. https://doi.org/10.7554/eLife.12748

    Article  PubMed  PubMed Central  Google Scholar 

  104. Prox J, Bernreuther C, Altmeppen H, Grendel J, Glatzel M, D’Hooge R, Stroobants S, Ahmed T, Balschun D, Willem M, Lammich S, Isbrandt D, Schweizer M, Horre K, De Strooper B, Saftig P (2013) Postnatal disruption of the disintegrin/metalloproteinase ADAM10 in brain causes epileptic seizures, learning deficits, altered spine morphology, and defective synaptic functions. J Neurosci 33(32):12915–12928, 12928a. https://doi.org/10.1523/JNEUROSCI.5910-12.2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Maretzky T, Evers A, Le Gall S, Alabi RO, Speck N, Reiss K, Blobel CP (2015) The cytoplasmic domain of a disintegrin and metalloproteinase 10 (ADAM10) regulates its constitutive activity but is dispensable for stimulated ADAM10-dependent shedding. J Biol Chem 290(12):7416–7425. https://doi.org/10.1074/jbc.M114.603753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Deng W, Cho S, Su PC, Berger BW, Li R (2014) Membrane-enabled dimerization of the intrinsically disordered cytoplasmic domain of ADAM10. Proc Natl Acad Sci USA 111(45):15987–15992. https://doi.org/10.1073/pnas.1409354111

    Article  CAS  PubMed  Google Scholar 

  107. Saftig P, Lichtenthaler SF (2015) The alpha secretase ADAM10: A metalloprotease with multiple functions in the brain. Prog Neurobiol 135:1–20. https://doi.org/10.1016/j.pneurobio.2015.10.003

    Article  CAS  PubMed  Google Scholar 

  108. Endres K, Fahrenholz F (2012) Regulation of alpha-secretase ADAM10 expression and activity. Exp Brain Res 217(3–4):343–352. https://doi.org/10.1007/s00221-011-2885-7

    Article  CAS  PubMed  Google Scholar 

  109. Vincent B (2016) Regulation of the alpha-secretase ADAM10 at transcriptional, translational and post-translational levels. Brain Res Bull 126(Pt 2):154–169. https://doi.org/10.1016/j.brainresbull.2016.03.020

    Article  CAS  PubMed  Google Scholar 

  110. Alabi RO, Farber G, Blobel CP (2018) Intriguing roles for endothelial ADAM10/notch signaling in the development of organ-specific vascular beds. Physiol Rev 98(4):2025–2061. https://doi.org/10.1152/physrev.00029.2017

    Article  CAS  PubMed  Google Scholar 

  111. Farber G, Parks MM, Lustgarten Guahmich N, Zhang Y, Monette S, Blanchard SC, Di Lorenzo A, Blobel CP (2018) ADAM10 controls the differentiation of the coronary arterial endothelium. Angiogenesis. https://doi.org/10.1007/s10456-018-9653-2

    Article  PubMed  PubMed Central  Google Scholar 

  112. Farber G, Hurtado R, Loh S, Monette S, Mtui J, Kopan R, Quaggin S, Meyer-Schwesinger C, Herzlinger D, Scott RP, Blobel CP (2018) Glomerular endothelial cell maturation depends on ADAM10, a key regulator of Notch signaling. Angiogenesis 21(2):335–347. https://doi.org/10.1007/s10456-018-9599-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Bray SJ (2016) Notch signalling in context. Nat Rev Mol Cell Biol 17(11):722–735. https://doi.org/10.1038/nrm.2016.94

    Article  CAS  PubMed  Google Scholar 

  114. Pan D, Rubin GM (1997) Kuzbanian controls proteolytic processing of Notch and mediates lateral inhibition during Drosophila and vertebrate neurogenesis. Cell 90(2):271–280

    Article  CAS  Google Scholar 

  115. Rooke J, Pan D, Xu T, Rubin GM (1996) KUZ, a conserved metalloprotease–disintegrin protein with two roles in Drosophila neurogenesis. Science (New York, NY) 273(5279):1227–1231

    Article  CAS  Google Scholar 

  116. Hartmann D, de Strooper B, Serneels L, Craessaerts K, Herreman A, Annaert W, Umans L, Lubke T, Lena Illert A, von Figura K, Saftig P (2002) The disintegrin/metalloprotease ADAM 10 is essential for Notch signalling but not for alpha-secretase activity in fibroblasts. Hum Mol Genet 11(21):2615–2624

    Article  CAS  Google Scholar 

  117. Yang Z, Li PF, Chen RC, Wang J, Wang S, Shen Y, Wu X, Fang B, Cheng X, Xiong ZQ (2017) ADAM10-initiated release of notch intracellular domain regulates microtubule stability and radial migration of cortical neurons. Cereb Cortex 27(2):919–932. https://doi.org/10.1093/cercor/bhx006

    Article  PubMed  PubMed Central  Google Scholar 

  118. Chilton JK (2006) Molecular mechanisms of axon guidance. Dev Biol 292(1):13–24. https://doi.org/10.1016/j.ydbio.2005.12.048

    Article  CAS  PubMed  Google Scholar 

  119. Hattori M, Osterfield M, Flanagan JG (2000) Regulated cleavage of a contact-mediated axon repellent. Science (New York, NY) 289(5483):1360–1365

    Article  CAS  Google Scholar 

  120. Janes PW, Saha N, Barton WA, Kolev MV, Wimmer-Kleikamp SH, Nievergall E, Blobel CP, Himanen JP, Lackmann M, Nikolov DB (2005) Adam meets Eph: an ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans. Cell 123(2):291–304. https://doi.org/10.1016/j.cell.2005.08.014

    Article  CAS  PubMed  Google Scholar 

  121. Brennaman LH, Moss ML, Maness PF (2014) EphrinA/EphA-induced ectodomain shedding of neural cell adhesion molecule regulates growth cone repulsion through ADAM10 metalloprotease. J Neurochem 128(2):267–279. https://doi.org/10.1111/jnc.12468

    Article  CAS  PubMed  Google Scholar 

  122. Hinkle CL, Diestel S, Lieberman J, Maness PF (2006) Metalloprotease-induced ectodomain shedding of neural cell adhesion molecule (NCAM). J Neurobiol 66(12):1378–1395. https://doi.org/10.1002/neu.20257

    Article  CAS  PubMed  Google Scholar 

  123. Romi E, Gokhman I, Wong E, Antonovsky N, Ludwig A, Sagi I, Saftig P, Tessier-Lavigne M, Yaron A (2014) ADAM metalloproteases promote a developmental switch in responsiveness to the axonal repellant Sema3A. Nat Commun 5:4058. https://doi.org/10.1038/ncomms5058

    Article  CAS  PubMed  Google Scholar 

  124. Heyden A, Angenstein F, Sallaz M, Seidenbecher C, Montag D (2008) Abnormal axonal guidance and brain anatomy in mouse mutants for the cell recognition molecules close homolog of L1 and NgCAM-related cell adhesion molecule. Neuroscience 155(1):221–233. https://doi.org/10.1016/j.neuroscience.2008.04.080

    Article  CAS  PubMed  Google Scholar 

  125. Brummer T, Mueller SA, Pan-Montojo F, Yoshida F, Fellgiebel A, Tomita T, Endres K, Lichtenthaler SF (2019) NrCAM is a marker for substrate-selective activation of ADAM10 in Alzheimer’s disease. EMBO Mol Med 32(7):e9695

  126. Dalva MB, McClelland AC, Kayser MS (2007) Cell adhesion molecules: signalling functions at the synapse. Nat Rev Neurosci 8(3):206–220. https://doi.org/10.1038/nrn2075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Bell KF, Zheng L, Fahrenholz F, Cuello AC (2008) ADAM-10 over-expression increases cortical synaptogenesis. Neurobiol Aging 29(4):554–565. https://doi.org/10.1016/j.neurobiolaging.2006.11.004

    Article  CAS  PubMed  Google Scholar 

  128. Reiss K, Maretzky T, Ludwig A, Tousseyn T, de Strooper B, Hartmann D, Saftig P (2005) ADAM10 cleavage of N-cadherin and regulation of cell-cell adhesion and beta-catenin nuclear signalling. EMBO J 24(4):742–752. https://doi.org/10.1038/sj.emboj.7600548

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Uemura K, Kihara T, Kuzuya A, Okawa K, Nishimoto T, Ninomiya H, Sugimoto H, Kinoshita A, Shimohama S (2006) Characterization of sequential N-cadherin cleavage by ADAM10 and PS1. Neurosci Lett 402(3):278–283. https://doi.org/10.1016/j.neulet.2006.04.018

    Article  CAS  PubMed  Google Scholar 

  130. Malinverno M, Carta M, Epis R, Marcello E, Verpelli C, Cattabeni F, Sala C, Mulle C, Di Luca M, Gardoni F (2010) Synaptic localization and activity of ADAM10 regulate excitatory synapses through N-cadherin cleavage. J Neurosci 30(48):16343–16355. https://doi.org/10.1523/JNEUROSCI.1984-10.2010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Suzuki K, Hayashi Y, Nakahara S, Kumazaki H, Prox J, Horiuchi K, Zeng M, Tanimura S, Nishiyama Y, Osawa S, Sehara-Fujisawa A, Saftig P, Yokoshima S, Fukuyama T, Matsuki N, Koyama R, Tomita T, Iwatsubo T (2012) Activity-dependent proteolytic cleavage of neuroligin-1. Neuron 76(2):410–422. https://doi.org/10.1016/j.neuron.2012.10.003

    Article  CAS  PubMed  Google Scholar 

  132. Bot N, Schweizer C, Ben Halima S, Fraering PC (2011) Processing of the synaptic cell adhesion molecule neurexin-3beta by Alzheimer disease alpha- and gamma-secretases. J Biol Chem 286(4):2762–2773. https://doi.org/10.1074/jbc.M110.142521

    Article  CAS  PubMed  Google Scholar 

  133. Borcel E, Palczynska M, Krzisch M, Dimitrov M, Ulrich G, Toni N, Fraering PC (2016) Shedding of neurexin 3beta ectodomain by ADAM10 releases a soluble fragment that affects the development of newborn neurons. Sci Rep 6:39310. https://doi.org/10.1038/srep39310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Venkatesh HS, Tam LT, Woo PJ, Lennon J, Nagaraja S, Gillespie SM, Ni J, Duveau DY, Morris PJ, Zhao JJ, Thomas CJ, Monje M (2017) Targeting neuronal activity-regulated neuroligin-3 dependency in high-grade glioma. Nature 549(7673):533–537. https://doi.org/10.1038/nature24014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Marcello E, Gardoni F, Mauceri D, Romorini S, Jeromin A, Epis R, Borroni B, Cattabeni F, Sala C, Padovani A, Di Luca M (2007) Synapse-associated protein-97 mediates alpha-secretase ADAM10 trafficking and promotes its activity. J Neurosci 27(7):1682–1691. https://doi.org/10.1523/JNEUROSCI.3439-06.2007

    Article  CAS  PubMed  Google Scholar 

  136. Lundgren JL, Ahmed S, Schedin-Weiss S, Gouras GK, Winblad B, Tjernberg LO, Frykman S (2015) ADAM10 and BACE1 are localized to synaptic vesicles. J Neurochem 135(3):606–615. https://doi.org/10.1111/jnc.13287

    Article  CAS  PubMed  Google Scholar 

  137. Sakry D, Neitz A, Singh J, Frischknecht R, Marongiu D, Biname F, Perera SS, Endres K, Lutz B, Radyushkin K, Trotter J, Mittmann T (2014) Oligodendrocyte precursor cells modulate the neuronal network by activity-dependent ectodomain cleavage of glial NG2. PLoS Biol 12(11):e1001993. https://doi.org/10.1371/journal.pbio.1001993

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Lammich S, Kojro E, Postina R, Gilbert S, Pfeiffer R, Jasionowski M, Haass C, Fahrenholz F (1999) Constitutive and regulated alpha-secretase cleavage of Alzheimer’s amyloid precursor protein by a disintegrin metalloprotease. Proc Natl Acad Sci USA 96(7):3922–3927

    Article  CAS  Google Scholar 

  139. Mattson MP, Cheng B, Culwell AR, Esch FS, Lieberburg I, Rydel RE (1993) Evidence for excitoprotective and intraneuronal calcium-regulating roles for secreted forms of the beta-amyloid precursor protein. Neuron 10(2):243–254

    Article  CAS  Google Scholar 

  140. Kim M, Suh J, Romano D, Truong MH, Mullin K, Hooli B, Norton D, Tesco G, Elliott K, Wagner SL, Moir RD, Becker KD, Tanzi RE (2009) Potential late-onset Alzheimer’s disease-associated mutations in the ADAM10 gene attenuate {alpha}-secretase activity. Hum Mol Genet 18(20):3987–3996. https://doi.org/10.1093/hmg/ddp323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Suh J, Choi SH, Romano DM, Gannon MA, Lesinski AN, Kim DY, Tanzi RE (2013) ADAM10 missense mutations potentiate beta-amyloid accumulation by impairing prodomain chaperone function. Neuron 80(2):385–401. https://doi.org/10.1016/j.neuron.2013.08.035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Moss ML, Bomar M, Liu Q, Sage H, Dempsey P, Lenhart PM, Gillispie PA, Stoeck A, Wildeboer D, Bartsch JW, Palmisano R, Zhou P (2007) The ADAM10 prodomain is a specific inhibitor of ADAM10 proteolytic activity and inhibits cellular shedding events. J Biol Chem 282(49):35712–35721. https://doi.org/10.1074/jbc.M703231200

    Article  CAS  PubMed  Google Scholar 

  143. Postina R, Schroeder A, Dewachter I, Bohl J, Schmitt U, Kojro E, Prinzen C, Endres K, Hiemke C, Blessing M, Flamez P, Dequenne A, Godaux E, van Leuven F, Fahrenholz F (2004) A disintegrin-metalloproteinase prevents amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model. J Clin Investig 113(10):1456–1464. https://doi.org/10.1172/JCI20864

    Article  CAS  PubMed  Google Scholar 

  144. Tippmann F, Hundt J, Schneider A, Endres K, Fahrenholz F (2009) Up-regulation of the alpha-secretase ADAM10 by retinoic acid receptors and acitretin. FASEB J 23(6):1643–1654. https://doi.org/10.1096/fj.08-121392

    Article  CAS  PubMed  Google Scholar 

  145. Endres K, Fahrenholz F, Lotz J, Hiemke C, Teipel S, Lieb K, Tuscher O, Fellgiebel A (2014) Increased CSF APPs-alpha levels in patients with Alzheimer disease treated with acitretin. Neurology 83(21):1930–1935. https://doi.org/10.1212/WNL.0000000000001017

    Article  CAS  PubMed  Google Scholar 

  146. Altmeppen HC, Prox J, Puig B, Kluth MA, Bernreuther C, Thurm D, Jorissen E, Petrowitz B, Bartsch U, De Strooper B, Saftig P, Glatzel M (2011) Lack of a-disintegrin-and-metalloproteinase ADAM10 leads to intracellular accumulation and loss of shedding of the cellular prion protein in vivo. Mol Neurodegener 6:36. https://doi.org/10.1186/1750-1326-6-36

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Linsenmeier L, Mohammadi B, Wetzel S, Puig B, Jackson WS, Hartmann A, Uchiyama K, Sakaguchi S, Endres K, Tatzelt J, Saftig P, Glatzel M, Altmeppen HC (2018) Structural and mechanistic aspects influencing the ADAM10-mediated shedding of the prion protein. Mol Neurodegener 13(1):18. https://doi.org/10.1186/s13024-018-0248-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Altmeppen HC, Prox J, Krasemann S, Puig B, Kruszewski K, Dohler F, Bernreuther C, Hoxha A, Linsenmeier L, Sikorska B, Liberski PP, Bartsch U, Saftig P, Glatzel M (2015) The sheddase ADAM10 is a potent modulator of prion disease. Elife 4:e04260. https://doi.org/10.7554/eLife.04260

    Article  CAS  PubMed Central  Google Scholar 

  149. Stoeck A, Keller S, Riedle S, Sanderson MP, Runz S, Le Naour F, Gutwein P, Ludwig A, Rubinstein E, Altevogt P (2006) A role for exosomes in the constitutive and stimulus-induced ectodomain cleavage of L1 and CD44. Biochem J 393(Pt 3):609–618. https://doi.org/10.1042/BJ20051013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Padro CJ, Shawler TM, Gormley MG, Sanders VM (2013) Adrenergic regulation of IgE involves modulation of CD23 and ADAM10 expression on exosomes. J Immunol 191(11):5383–5397. https://doi.org/10.4049/jimmunol.1301019

    Article  CAS  PubMed  Google Scholar 

  151. Zhang W, Zhang J, Cheng L, Ni H, You B, Shan Y, Bao L, Wu D, Zhang T, Yue H, Chen J (2018) A disintegrin and metalloprotease 10-containing exosomes derived from nasal polyps promote angiogenesis and vascular permeability. Mol Med Rep 17(4):5921–5927. https://doi.org/10.3892/mmr.2018.8634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Freese C, Garratt AN, Fahrenholz F, Endres K (2009) The effects of alpha-secretase ADAM10 on the proteolysis of neuregulin-1. FEBS J 276(6):1568–1580. https://doi.org/10.1111/j.1742-4658.2009.06889.x

    Article  CAS  PubMed  Google Scholar 

  153. Jangouk P, Dehmel T, Meyer Zu Horste G, Ludwig A, Lehmann HC, Kieseier BC (2009) Involvement of ADAM10 in axonal outgrowth and myelination of the peripheral nerve. Glia 57(16):1765–1774. https://doi.org/10.1002/glia.20889

    Article  PubMed  Google Scholar 

  154. Luo X, Prior M, He W, Hu X, Tang X, Shen W, Yadav S, Kiryu-Seo S, Miller R, Trapp BD, Yan R (2011) Cleavage of neuregulin-1 by BACE1 or ADAM10 protein produces differential effects on myelination. J Biol Chem 286(27):23967–23974. https://doi.org/10.1074/jbc.M111.251538

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Meyer Zu Horste G, Derksen A, Stassart R, Szepanowski F, Thanos M, Stettner M, Boettcher C, Lehmann HC, Hartung HP, Kieseier BC (2015) Neuronal ADAM10 promotes outgrowth of small-caliber myelinated axons in the peripheral nervous system. J Neuropathol Exp Neurol 74(11):1077–1085. https://doi.org/10.1097/NEN.0000000000000253

    Article  CAS  PubMed  Google Scholar 

  156. Colombo A, Hsia HE, Wang M, Kuhn PH, Brill MS, Canevazzi P, Feederle R, Taveggia C, Misgeld T, Lichtenthaler SF (2018) Non-cell-autonomous function of DR6 in Schwann cell proliferation. EMBO J 37(7):e97390. https://doi.org/10.15252/embj.201797390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Matthews AL, Szyroka J, Collier R, Noy PJ, Tomlinson MG (2017) Scissor sisters: regulation of ADAM10 by the TspanC8 tetraspanins. Biochem Soc Trans 45(3):719–730. https://doi.org/10.1042/BST20160290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Haining EJ, Yang J, Bailey RL, Khan K, Collier R, Tsai S, Watson SP, Frampton J, Garcia P, Tomlinson MG (2012) The TspanC8 subgroup of tetraspanins interacts with A disintegrin and metalloprotease 10 (ADAM10) and regulates its maturation and cell surface expression. J Biol Chem 287(47):39753–39765. https://doi.org/10.1074/jbc.M112.416503

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Noy PJ, Yang J, Reyat JS, Matthews AL, Charlton AE, Furmston J, Rogers DA, Rainger GE, Tomlinson MG (2016) TspanC8 tetraspanins and A Disintegrin and Metalloprotease 10 (ADAM10) interact via their extracellular regions: evidence for distinct binding mechanisms for different TspanC8 proteins. J Biol Chem 291(7):3145–3157. https://doi.org/10.1074/jbc.M115.703058

    Article  CAS  PubMed  Google Scholar 

  160. Jouannet S, Saint-Pol J, Fernandez L, Nguyen V, Charrin S, Boucheix C, Brou C, Milhiet PE, Rubinstein E (2016) TspanC8 tetraspanins differentially regulate the cleavage of ADAM10 substrates, Notch activation and ADAM10 membrane compartmentalization. Cell Mol Life Sci 73(9):1895–1915. https://doi.org/10.1007/s00018-015-2111-z

    Article  CAS  PubMed  Google Scholar 

  161. Seipold L, Altmeppen H, Koudelka T, Tholey A, Kasparek P, Sedlacek R, Schweizer M, Bar J, Mikhaylova M, Glatzel M, Saftig P (2018) In vivo regulation of the A disintegrin and metalloproteinase 10 (ADAM10) by the tetraspanin 15. Cell Mol Life Sci 75(17):3251–3267. https://doi.org/10.1007/s00018-018-2791-2

    Article  CAS  PubMed  Google Scholar 

  162. Bernstein HG, Keilhoff G, Bukowska A, Ziegeler A, Funke S, Dobrowolny H, Kanakis D, Bogerts B, Lendeckel U (2004) ADAM (a disintegrin and metalloprotease) 12 is expressed in rat and human brain and localized to oligodendrocytes. J Neurosci Res 75(3):353–360. https://doi.org/10.1002/jnr.10858

    Article  CAS  PubMed  Google Scholar 

  163. Kveiborg M, Albrechtsen R, Rudkjaer L, Wen G, Damgaard-Pedersen K, Wewer UM (2006) ADAM12-S stimulates bone growth in transgenic mice by modulating chondrocyte proliferation and maturation. J Bone Miner Res 21(8):1288–1296. https://doi.org/10.1359/jbmr.060502

    Article  CAS  PubMed  Google Scholar 

  164. Cao Y, Zhao Z, Gruszczynska-Biegala J, Zolkiewska A (2003) Role of metalloprotease disintegrin ADAM12 in determination of quiescent reserve cells during myogenic differentiation in vitro. Mol Cell Biol 23(19):6725–6738

    Article  CAS  Google Scholar 

  165. Kurisaki T, Masuda A, Sudo K, Sakagami J, Higashiyama S, Matsuda Y, Nagabukuro A, Tsuji A, Nabeshima Y, Asano M, Iwakura Y, Sehara-Fujisawa A (2003) Phenotypic analysis of Meltrin alpha (ADAM12)-deficient mice: involvement of Meltrin alpha in adipogenesis and myogenesis. Mol Cell Biol 23(1):55–61

    Article  CAS  Google Scholar 

  166. Malinin NL, Wright S, Seubert P, Schenk D, Griswold-Prenner I (2005) Amyloid-beta neurotoxicity is mediated by FISH adapter protein and ADAM12 metalloprotease activity. Proc Natl Acad Sci USA 102(8):3058–3063. https://doi.org/10.1073/pnas.0408237102

    Article  CAS  PubMed  Google Scholar 

  167. Selvais C, D’Auria L, Tyteca D, Perrot G, Lemoine P, Troeberg L, Dedieu S, Noel A, Nagase H, Henriet P, Courtoy PJ, Marbaix E, Emonard H (2011) Cell cholesterol modulates metalloproteinase-dependent shedding of low-density lipoprotein receptor-related protein-1 (LRP-1) and clearance function. FASEB J 25(8):2770–2781. https://doi.org/10.1096/fj.10-169508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Cui D, Arima M, Takubo K, Kimura T, Horiuchi K, Minagawa T, Matsuda S, Ikeda E (2015) ADAM12 and ADAM17 are essential molecules for hypoxia-induced impairment of neural vascular barrier function. Sci Rep 5:12796. https://doi.org/10.1038/srep12796

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Black RA, Rauch CT, Kozlosky CJ, Peschon JJ, Slack JL, Wolfson MF, Castner BJ, Stocking KL, Reddy P, Srinivasan S, Nelson N, Boiani N, Schooley KA, Gerhart M, Davis R, Fitzner JN, Johnson RS, Paxton RJ, March CJ, Cerretti DP (1997) A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells. Nature 385(6618):729–733. https://doi.org/10.1038/385729a0

    Article  CAS  PubMed  Google Scholar 

  170. Moss ML, Jin SL, Milla ME, Bickett DM, Burkhart W, Carter HL, Chen WJ, Clay WC, Didsbury JR, Hassler D, Hoffman CR, Kost TA, Lambert MH, Leesnitzer MA, McCauley P, McGeehan G, Mitchell J, Moyer M, Pahel G, Rocque W, Overton LK, Schoenen F, Seaton T, Su JL, Becherer JD et al (1997) Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha. Nature 385(6618):733–736. https://doi.org/10.1038/385733a0

    Article  CAS  PubMed  Google Scholar 

  171. Zunke F, Rose-John S (2017) The shedding protease ADAM17: Physiology and pathophysiology. Biochim Biophys Acta 1864(11 Pt B):2059–2070. https://doi.org/10.1016/j.bbamcr.2017.07.001

    Article  CAS  Google Scholar 

  172. Reddy P, Slack JL, Davis R, Cerretti DP, Kozlosky CJ, Blanton RA, Shows D, Peschon JJ, Black RA (2000) Functional analysis of the domain structure of tumor necrosis factor-alpha converting enzyme. J Biol Chem 275(19):14608–14614

    Article  CAS  Google Scholar 

  173. Le Gall SM, Maretzky T, Issuree PD, Niu XD, Reiss K, Saftig P, Khokha R, Lundell D, Blobel CP (2010) ADAM17 is regulated by a rapid and reversible mechanism that controls access to its catalytic site. J Cell Sci 123(Pt 22):3913–3922. https://doi.org/10.1242/jcs.069997

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Doedens JR, Mahimkar RM, Black RA (2003) TACE/ADAM-17 enzymatic activity is increased in response to cellular stimulation. Biochem Biophys Res Commun 308(2):331–338

    Article  CAS  Google Scholar 

  175. Li Q, Zhang Z, Li Z, Zhou M, Liu B, Pan L, Ma Z, Zheng Y (2013) ADAM17 is critical for multipolar exit and radial migration of neuronal intermediate progenitor cells in mice cerebral cortex. PLoS One 8(6):e65703. https://doi.org/10.1371/journal.pone.0065703

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Peschon JJ, Slack JL, Reddy P, Stocking KL, Sunnarborg SW, Lee DC, Russell WE, Castner BJ, Johnson RS, Fitzner JN, Boyce RW, Nelson N, Kozlosky CJ, Wolfson MF, Rauch CT, Cerretti DP, Paxton RJ, March CJ, Black RA (1998) An essential role for ectodomain shedding in mammalian development. Science (New York, NY) 282(5392):1281–1284

    Article  CAS  Google Scholar 

  177. Blobel CP (2005) ADAMs: key components in EGFR signalling and development. Nat Rev Mol Cell Biol 6(1):32–43. https://doi.org/10.1038/nrm1548

    Article  CAS  PubMed  Google Scholar 

  178. Jackson LF, Qiu TH, Sunnarborg SW, Chang A, Zhang C, Patterson C, Lee DC (2003) Defective valvulogenesis in HB-EGF and TACE-null mice is associated with aberrant BMP signaling. EMBO J 22(11):2704–2716. https://doi.org/10.1093/emboj/cdg264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Mine N, Iwamoto R, Mekada E (2005) HB-EGF promotes epithelial cell migration in eyelid development. Development 132(19):4317–4326. https://doi.org/10.1242/dev.02030

    Article  CAS  PubMed  Google Scholar 

  180. Threadgill DW, Dlugosz AA, Hansen LA, Tennenbaum T, Lichti U, Yee D, LaMantia C, Mourton T, Herrup K, Harris RC et al (1995) Targeted disruption of mouse EGF receptor: effect of genetic background on mutant phenotype. Science (New York, NY) 269(5221):230–234

    Article  CAS  Google Scholar 

  181. Miettinen PJ, Berger JE, Meneses J, Phung Y, Pedersen RA, Werb Z, Derynck R (1995) Epithelial immaturity and multiorgan failure in mice lacking epidermal growth factor receptor. Nature 376(6538):337–341. https://doi.org/10.1038/376337a0

    Article  CAS  PubMed  Google Scholar 

  182. Oyagi A, Moriguchi S, Nitta A, Murata K, Oida Y, Tsuruma K, Shimazawa M, Fukunaga K, Hara H (2011) Heparin-binding EGF-like growth factor is required for synaptic plasticity and memory formation. Brain Res 1419:97–104. https://doi.org/10.1016/j.brainres.2011.09.003

    Article  CAS  PubMed  Google Scholar 

  183. Palazuelos J, Crawford HC, Klingener M, Sun B, Karelis J, Raines EW, Aguirre A (2014) TACE/ADAM17 is essential for oligodendrocyte development and CNS myelination. J Neurosci 34(36):11884–11896. https://doi.org/10.1523/JNEUROSCI.1220-14.2014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Palazuelos J, Klingener M, Raines EW, Crawford HC, Aguirre A (2015) Oligodendrocyte regeneration and CNS remyelination require TACE/ADAM17. J Neurosci 35(35):12241–12247. https://doi.org/10.1523/JNEUROSCI.3937-14.2015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. La Marca R, Cerri F, Horiuchi K, Bachi A, Feltri ML, Wrabetz L, Blobel CP, Quattrini A, Salzer JL, Taveggia C (2011) TACE (ADAM17) inhibits Schwann cell myelination. Nat Neurosci 14(7):857–865. https://doi.org/10.1038/nn.2849

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Iwakura Y, Wang R, Inamura N, Araki K, Higashiyama S, Takei N, Nawa H (2017) Glutamate-dependent ectodomain shedding of neuregulin-1 type II precursors in rat forebrain neurons. PLoS One 12(3):e0174780. https://doi.org/10.1371/journal.pone.0174780

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Kim J, Elias A, Lee T, Maurel P, Kim HA (2017) Tissue inhibitor of metalloproteinase-3 promotes schwann cell myelination. ASN Neuro 9(6):1759091417745425. https://doi.org/10.1177/1759091417745425

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Fleck D, van Bebber F, Colombo A, Galante C, Schwenk BM, Rabe L, Hampel H, Novak B, Kremmer E, Tahirovic S, Edbauer D, Lichtenthaler SF, Schmid B, Willem M, Haass C (2013) Dual cleavage of neuregulin 1 type III by BACE1 and ADAM17 liberates its EGF-like domain and allows paracrine signaling. J Neurosci 33(18):7856–7869. https://doi.org/10.1523/JNEUROSCI.3372-12.2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Cho RW, Park JM, Wolff SB, Xu D, Hopf C, Kim JA, Reddy RC, Petralia RS, Perin MS, Linden DJ, Worley PF (2008) mGluR1/5-dependent long-term depression requires the regulated ectodomain cleavage of neuronal pentraxin NPR by TACE. Neuron 57(6):858–871. https://doi.org/10.1016/j.neuron.2008.01.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  190. Okamura Y, Kohmura E, Yamashita T (2011) TACE cleaves neogenin to desensitize cortical neurons to the repulsive guidance molecule. Neurosci Res 71(1):63–70. https://doi.org/10.1016/j.neures.2011.05.012

    Article  CAS  PubMed  Google Scholar 

  191. van Erp S, van den Heuvel DMA, Fujita Y, Robinson RA, Hellemons A, Adolfs Y, Van Battum EY, Blokhuis AM, Kuijpers M, Demmers JAA, Hedman H, Hoogenraad CC, Siebold C, Yamashita T, Pasterkamp RJ (2015) Lrig2 negatively regulates ectodomain shedding of axon guidance receptors by ADAM proteases. Dev Cell 35(5):537–552. https://doi.org/10.1016/j.devcel.2015.11.008

    Article  CAS  PubMed  Google Scholar 

  192. Weskamp G, Schlondorff J, Lum L, Becherer JD, Kim TW, Saftig P, Hartmann D, Murphy G, Blobel CP (2004) Evidence for a critical role of the tumor necrosis factor alpha convertase (TACE) in ectodomain shedding of the p75 neurotrophin receptor (p75NTR). J Biol Chem 279(6):4241–4249. https://doi.org/10.1074/jbc.M307974200

    Article  CAS  PubMed  Google Scholar 

  193. Kalus I, Bormann U, Mzoughi M, Schachner M, Kleene R (2006) Proteolytic cleavage of the neural cell adhesion molecule by ADAM17/TACE is involved in neurite outgrowth. J Neurochem 98(1):78–88. https://doi.org/10.1111/j.1471-4159.2006.03847.x

    Article  CAS  PubMed  Google Scholar 

  194. Shirakabe K, Omura T, Shibagaki Y, Mihara E, Homma K, Kato Y, Yoshimura A, Murakami Y, Takagi J, Hattori S, Ogawa Y (2017) Mechanistic insights into ectodomain shedding: susceptibility of CADM1 adhesion molecule is determined by alternative splicing and O-glycosylation. Sci Rep 7:46174. https://doi.org/10.1038/srep46174

  195. Xia H, Sriramula S, Chhabra KH, Lazartigues E (2013) Brain angiotensin-converting enzyme type 2 shedding contributes to the development of neurogenic hypertension. Circ Res 113(9):1087–1096. https://doi.org/10.1161/CIRCRESAHA.113.301811

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  196. Xu J, Sriramula S, Lazartigues E (2018) Excessive glutamate stimulation impairs ACE2 activity through ADAM17-mediated shedding in cultured cortical neurons. Cell Mol Neurobiol. https://doi.org/10.1007/s10571-018-0591-8

    Article  PubMed  Google Scholar 

  197. Siney EJ, Holden A, Casselden E, Bulstrode H, Thomas GJ, Willaime-Morawek S (2017) Metalloproteinases ADAM10 and ADAM17 mediate migration and differentiation in glioblastoma sphere-forming cells. Mol Neurobiol 54(5):3893–3905. https://doi.org/10.1007/s12035-016-0053-6

    Article  CAS  PubMed  Google Scholar 

  198. Honda H, Takamura M, Yamagiwa S, Genda T, Horigome R, Kimura N, Setsu T, Tominaga K, Kamimura H, Matsuda Y, Wakai T, Aoyagi Y, Terai S (2017) Overexpression of a disintegrin and metalloproteinase 21 is associated with motility, metastasis, and poor prognosis in hepatocellular carcinoma. Sci Rep 7(1):15485. https://doi.org/10.1038/s41598-017-15800-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  199. Nandhu MS, Kwiatkowska A, Bhaskaran V, Hayes J, Hu B, Viapiano MS (2017) Tumor-derived fibulin-3 activates pro-invasive NF-kappaB signaling in glioblastoma cells and their microenvironment. Oncogene 36(34):4875–4886. https://doi.org/10.1038/onc.2017.109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  200. Vincent B, Cisse MA, Sunyach C, Guillot-Sestier MV, Checler F (2008) Regulation of betaAPP and PrPc cleavage by alpha-secretase: mechanistic and therapeutic perspectives. Curr Alzheimer Res 5(2):202–211

    Article  CAS  Google Scholar 

  201. Caccamo A, Oddo S, Billings LM, Green KN, Martinez-Coria H, Fisher A, LaFerla FM (2006) M1 receptors play a central role in modulating AD-like pathology in transgenic mice. Neuron 49(5):671–682. https://doi.org/10.1016/j.neuron.2006.01.020

    Article  CAS  PubMed  Google Scholar 

  202. Nitsch RM, Slack BE, Wurtman RJ, Growdon JH (1992) Release of Alzheimer amyloid precursor derivatives stimulated by activation of muscarinic acetylcholine receptors. Science (New York, NY) 258(5080):304–307

    Article  CAS  Google Scholar 

  203. Buxbaum JD, Liu KN, Luo Y, Slack JL, Stocking KL, Peschon JJ, Johnson RS, Castner BJ, Cerretti DP, Black RA (1998) Evidence that tumor necrosis factor alpha converting enzyme is involved in regulated alpha-secretase cleavage of the Alzheimer amyloid protein precursor. J Biol Chem 273(43):27765–27767

    Article  CAS  Google Scholar 

  204. Hartl D, May P, Gu W, Mayhaus M, Pichler S, Spaniol C, Glaab E, Bobbili DR, Antony P, Koegelsberger S, Kurz A, Grimmer T, Morgan K, Vardarajan BN, Reitz C, Hardy J, Bras J, Guerreiro R, Balling R, Schneider JG, Riemenschneider M, AESG Consortium (2018) A rare loss-of-function variant of ADAM17 is associated with late-onset familial Alzheimer disease. Mol Psychiatry. https://doi.org/10.1038/s41380-018-0091-8

    Article  PubMed  Google Scholar 

  205. Cai Z, Wang C, He W, Chen Y (2018) Berberine alleviates amyloid-beta pathology in the brain of APP/PS1 transgenic mice via inhibiting beta/gamma-secretases activity and enhancing alpha-secretases. Curr Alzheimer Res. https://doi.org/10.2174/1567205015666180702105740

    Article  PubMed  Google Scholar 

  206. Giuliani F, Vernay A, Leuba G, Schenk F (2009) Decreased behavioral impairments in an Alzheimer mice model by interfering with TNF-alpha metabolism. Brain Res Bull 80(4–5):302–308. https://doi.org/10.1016/j.brainresbull.2009.07.009

    Article  CAS  PubMed  Google Scholar 

  207. Lourenco MV, Clarke JR, Frozza RL, Bomfim TR, Forny-Germano L, Batista AF, Sathler LB, Brito-Moreira J, Amaral OB, Silva CA, Freitas-Correa L, Espirito-Santo S, Campello-Costa P, Houzel JC, Klein WL, Holscher C, Carvalheira JB, Silva AM, Velloso LA, Munoz DP, Ferreira ST, De Felice FG (2013) TNF-alpha mediates PKR-dependent memory impairment and brain IRS-1 inhibition induced by Alzheimer’s beta-amyloid oligomers in mice and monkeys. Cell Metab 18(6):831–843. https://doi.org/10.1016/j.cmet.2013.11.002

    Article  CAS  PubMed  Google Scholar 

  208. Shi JQ, Shen W, Chen J, Wang BR, Zhong LL, Zhu YW, Zhu HQ, Zhang QQ, Zhang YD, Xu J (2011) Anti-TNF-alpha reduces amyloid plaques and tau phosphorylation and induces CD11c-positive dendritic-like cell in the APP/PS1 transgenic mouse brains. Brain Res 1368:239–247. https://doi.org/10.1016/j.brainres.2010.10.053

    Article  CAS  PubMed  Google Scholar 

  209. Tobinick EL, Gross H (2008) Rapid cognitive improvement in Alzheimer’s disease following perispinal etanercept administration. J Neuroinflammation 5:2. https://doi.org/10.1186/1742-2094-5-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  210. Shi JQ, Wang BR, Jiang WW, Chen J, Zhu YW, Zhong LL, Zhang YD, Xu J (2011) Cognitive improvement with intrathecal administration of infliximab in a woman with Alzheimer’s disease. J Am Geriatr Soc 59(6):1142–1144. https://doi.org/10.1111/j.1532-5415.2011.03445.x

    Article  PubMed  Google Scholar 

  211. Feuerbach D, Schindler P, Barske C, Joller S, Beng-Louka E, Worringer KA, Kommineni S, Kaykas A, Ho DJ, Ye C, Welzenbach K, Elain G, Klein L, Brzak I, Mir AK, Farady CJ, Aichholz R, Popp S, George N, Neumann U (2017) ADAM17 is the main sheddase for the generation of human triggering receptor expressed in myeloid cells (hTREM2) ectodomain and cleaves TREM2 after Histidine 157. Neurosci Lett 660:109–114. https://doi.org/10.1016/j.neulet.2017.09.034

    Article  CAS  PubMed  Google Scholar 

  212. Schlepckow K, Kleinberger G, Fukumori A, Feederle R, Lichtenthaler SF, Steiner H, Haass C (2017) An Alzheimer-associated TREM2 variant occurs at the ADAM cleavage site and affects shedding and phagocytic function. EMBO Mol Med 9(10):1356–1365. https://doi.org/10.15252/emmm.201707672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  213. Thornton P, Sevalle J, Deery MJ, Fraser G, Zhou Y, Stahl S, Franssen EH, Dodd RB, Qamar S, Gomez Perez-Nievas B, Nicol LS, Eketjall S, Revell J, Jones C, Billinton A, St George-Hyslop PH, Chessell I, Crowther DC (2017) TREM2 shedding by cleavage at the H157-S158 bond is accelerated for the Alzheimer’s disease-associated H157Y variant. EMBO Mol Med 9(10):1366–1378. https://doi.org/10.15252/emmm.201707673

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  214. Song WM, Joshita S, Zhou Y, Ulland TK, Gilfillan S, Colonna M (2018) Humanized TREM2 mice reveal microglia-intrinsic and -extrinsic effects of R47H polymorphism. J Exp Med 215(3):745–760. https://doi.org/10.1084/jem.20171529

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  215. Jonsson T, Stefansson H, Steinberg S, Jonsdottir I, Jonsson PV, Snaedal J, Bjornsson S, Huttenlocher J, Levey AI, Lah JJ, Rujescu D, Hampel H, Giegling I, Andreassen OA, Engedal K, Ulstein I, Djurovic S, Ibrahim-Verbaas C, Hofman A, Ikram MA, van Duijn CM, Thorsteinsdottir U, Kong A, Stefansson K (2013) Variant of TREM2 associated with the risk of Alzheimer’s disease. N Engl J Med 368(2):107–116. https://doi.org/10.1056/NEJMoa1211103

    Article  CAS  PubMed  Google Scholar 

  216. Guerreiro R, Wojtas A, Bras J, Carrasquillo M, Rogaeva E, Majounie E, Cruchaga C, Sassi C, Kauwe JS, Younkin S, Hazrati L, Collinge J, Pocock J, Lashley T, Williams J, Lambert JC, Amouyel P, Goate A, Rademakers R, Morgan K, Powell J, St George-Hyslop P, Singleton A, Hardy J, Alzheimer Genetic Analysis G (2013) TREM2 variants in Alzheimer’s disease. N Engl J Med 368(2):117–127. https://doi.org/10.1056/NEJMoa1211851

    Article  CAS  PubMed  Google Scholar 

  217. Weinger JG, Omari KM, Marsden K, Raine CS, Shafit-Zagardo B (2009) Up-regulation of soluble Axl and Mer receptor tyrosine kinases negatively correlates with Gas6 in established multiple sclerosis lesions. Am J Pathol 175(1):283–293. https://doi.org/10.2353/ajpath.2009.080807

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  218. Qing X, Rogers L, Mortha A, Lavin Y, Redecha P, Issuree PD, Maretzky T, Merad M, McIlwain D, Mak TW, Overall CM, Blobel CP, Salmon JE (2016) iRhom2 regulates CSF1R cell surface expression and non-steady state myelopoiesis in mice. Eur J Immunol 46(12):2737–2748. https://doi.org/10.1002/eji.201646482

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  219. Sassi C, Nalls MA, Ridge PG, Gibbs JR, Lupton MK, Troakes C, Lunnon K, Al-Sarraj S, Brown KS, Medway C, Lord J, Turton J, Bras J, ARUK Consortium, Blumenau S, Thielke M, Josties C, Freyer D, Dietrich A, Hammer M, Baier M, Dirnagl U, Morgan K, Powell JF, Kauwe JS, Cruchaga C, Goate AM, Singleton AB, Guerreiro R, Hodges A, Hardy J (2018) Mendelian adult-onset leukodystrophy genes in Alzheimer’s disease: critical influence of CSF1R and NOTCH3. Neurobiol Aging 66:179 e117–179 e129. https://doi.org/10.1016/j.neurobiolaging.2018.01.015

    Article  CAS  Google Scholar 

  220. Liu Q, Zhang J, Tran H, Verbeek MM, Reiss K, Estus S, Bu G (2009) LRP1 shedding in human brain: roles of ADAM10 and ADAM17. Mol Neurodegeneration 4(1):17

  221. Wong E, Maretzky T, Peleg Y, Blobel CP, Sagi I (2015) The functional maturation of a disintegrin and metalloproteinase (ADAM) 9, 10, and 17 requires processing at a newly identified proprotein convertase (PC) cleavage site. J Biol Chem 290(19):12135–12146. https://doi.org/10.1074/jbc.M114.624072

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  222. Amour A, Slocombe PM, Webster A, Butler M, Knight CG, Smith BJ, Stephens PE, Shelley C, Hutton M, Knauper V, Docherty AJ, Murphy G (1998) TNF-alpha converting enzyme (TACE) is inhibited by TIMP-3. FEBS Lett 435(1):39–44

    Article  CAS  Google Scholar 

  223. Capone C, Dabertrand F, Baron-Menguy C, Chalaris A, Ghezali L, Domenga-Denier V, Schmidt S, Huneau C, Rose-John S, Nelson MT, Joutel A (2016) Mechanistic insights into a TIMP3-sensitive pathway constitutively engaged in the regulation of cerebral hemodynamics. Elife 5:e17536. https://doi.org/10.7554/eLife.17536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  224. Cavadas M, Oikonomidi I, Gaspar CJ, Burbridge E, Badenes M, Felix I, Bolado A, Hu T, Bileck A, Gerner C, Domingos PM, von Kriegsheim A, Adrain C (2017) Phosphorylation of iRhom2 controls stimulated proteolytic shedding by the metalloprotease ADAM17/TACE. Cell Rep 21(3):745–757. https://doi.org/10.1016/j.celrep.2017.09.074

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  225. Maretzky T, McIlwain DR, Issuree PD, Li X, Malapeira J, Amin S, Lang PA, Mak TW, Blobel CP (2013) iRhom2 controls the substrate selectivity of stimulated ADAM17-dependent ectodomain shedding. Proc Natl Acad Sci USA 110(28):11433–11438. https://doi.org/10.1073/pnas.1302553110

    Article  PubMed  Google Scholar 

  226. Li X, Maretzky T, Weskamp G, Monette S, Qing X, Issuree PD, Crawford HC, McIlwain DR, Mak TW, Salmon JE, Blobel CP (2015) iRhoms 1 and 2 are essential upstream regulators of ADAM17-dependent EGFR signaling. Proc Natl Acad Sci USA 112(19):6080–6085. https://doi.org/10.1073/pnas.1505649112

    Article  CAS  PubMed  Google Scholar 

  227. Adrain C, Zettl M, Christova Y, Taylor N, Freeman M (2012) Tumor necrosis factor signaling requires iRhom2 to promote trafficking and activation of TACE. Science (New York, NY) 335(6065):225–228. https://doi.org/10.1126/science.1214400

    Article  CAS  Google Scholar 

  228. McIlwain DR, Lang PA, Maretzky T, Hamada K, Ohishi K, Maney SK, Berger T, Murthy A, Duncan G, Xu HC, Lang KS, Haussinger D, Wakeham A, Itie-Youten A, Khokha R, Ohashi PS, Blobel CP, Mak TW (2012) iRhom2 regulation of TACE controls TNF-mediated protection against Listeria and responses to LPS. Science (New York, NY) 335(6065):229–232. https://doi.org/10.1126/science.1214448

    Article  CAS  Google Scholar 

  229. Christova Y, Adrain C, Bambrough P, Ibrahim A, Freeman M (2013) Mammalian iRhoms have distinct physiological functions including an essential role in TACE regulation. EMBO Rep 14(10):884–890. https://doi.org/10.1038/embor.2013.128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  230. Lichtenthaler SF, O’Hara BF, Blobel CP (2015) iRhoms in the brain—a new frontier? Cell Cycle 14(19):3003–3004. https://doi.org/10.1080/15384101.2015.1084187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  231. De Jager PL, Srivastava G, Lunnon K, Burgess J, Schalkwyk LC, Yu L, Eaton ML, Keenan BT, Ernst J, McCabe C, Tang A, Raj T, Replogle J, Brodeur W, Gabriel S, Chai HS, Younkin C, Younkin SG, Zou F, Szyf M, Epstein CB, Schneider JA, Bernstein BE, Meissner A, Ertekin-Taner N, Chibnik LB, Kellis M, Mill J, Bennett DA (2014) Alzheimer’s disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci. Nat Neurosci 17(9):1156–1163. https://doi.org/10.1038/nn.3786

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  232. Veroni C, Gabriele L, Canini I, Castiello L, Coccia E, Remoli ME, Columba-Cabezas S, Arico E, Aloisi F, Agresti C (2010) Activation of TNF receptor 2 in microglia promotes induction of anti-inflammatory pathways. Mol Cell Neurosci 45(3):234–244. https://doi.org/10.1016/j.mcn.2010.06.014

    Article  CAS  PubMed  Google Scholar 

  233. Chesneau V, Becherer JD, Zheng Y, Erdjument-Bromage H, Tempst P, Blobel CP (2003) Catalytic properties of ADAM19. J Biol Chem 278(25):22331–22340. https://doi.org/10.1074/jbc.M302781200

    Article  CAS  PubMed  Google Scholar 

  234. Zheng Y, Saftig P, Hartmann D, Blobel C (2004) Evaluation of the contribution of different ADAMs to tumor necrosis factor alpha (TNFalpha) shedding and of the function of the TNFalpha ectodomain in ensuring selective stimulated shedding by the TNFalpha convertase (TACE/ADAM17). J Biol Chem 279(41):42898–42906. https://doi.org/10.1074/jbc.M403193200

    Article  CAS  PubMed  Google Scholar 

  235. Kurisaki T, Masuda A, Osumi N, Nabeshima Y, Fujisawa-Sehara A (1998) Spatially- and temporally-restricted expression of meltrin alpha (ADAM12) and beta (ADAM19) in mouse embryo. Mech Dev 73(2):211–215

    Article  CAS  Google Scholar 

  236. Meyer D, Birchmeier C (1994) Distinct isoforms of neuregulin are expressed in mesenchymal and neuronal cells during mouse development. Proc Natl Acad Sci USA 91(3):1064–1068

    Article  CAS  Google Scholar 

  237. Zhou HM, Weskamp G, Chesneau V, Sahin U, Vortkamp A, Horiuchi K, Chiusaroli R, Hahn R, Wilkes D, Fisher P, Baron R, Manova K, Basson CT, Hempstead B, Blobel CP (2004) Essential role for ADAM19 in cardiovascular morphogenesis. Mol Cell Biol 24(1):96–104

    Article  CAS  Google Scholar 

  238. Shirakabe K, Wakatsuki S, Kurisaki T, Fujisawa-Sehara A (2001) Roles of Meltrin beta /ADAM19 in the processing of neuregulin. J Biol Chem 276(12):9352–9358. https://doi.org/10.1074/jbc.M007913200

    Article  CAS  PubMed  Google Scholar 

  239. Wakatsuki S, Yumoto N, Komatsu K, Araki T, Sehara-Fujisawa A (2009) Roles of meltrin-beta/ADAM19 in progression of Schwann cell differentiation and myelination during sciatic nerve regeneration. J Biol Chem 284(5):2957–2966. https://doi.org/10.1074/jbc.M803191200

    Article  CAS  PubMed  Google Scholar 

  240. Yumoto N, Wakatsuki S, Kurisaki T, Hara Y, Osumi N, Frisen J, Sehara-Fujisawa A (2008) Meltrin beta/ADAM19 interacting with EphA4 in developing neural cells participates in formation of the neuromuscular junction. PLoS One 3(10):e3322. https://doi.org/10.1371/journal.pone.0003322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  241. Tanabe C, Hotoda N, Sasagawa N, Sehara-Fujisawa A, Maruyama K, Ishiura S (2007) ADAM19 is tightly associated with constitutive Alzheimer’s disease APP alpha-secretase in A172 cells. Biochem Biophys Res Commun 352(1):111–117. https://doi.org/10.1016/j.bbrc.2006.10.181

    Article  CAS  PubMed  Google Scholar 

  242. Hooft van Huijsduijnen R (1998) ADAM 20 and 21; two novel human testis-specific membrane metalloproteases with similarity to fertilin-alpha. Gene 206(2):273–282

    Article  CAS  Google Scholar 

  243. Poindexter K, Nelson N, DuBose RF, Black RA, Cerretti DP (1999) The identification of seven metalloproteinase-disintegrin (ADAM) genes from genomic libraries. Gene 237(1):61–70

    Article  CAS  Google Scholar 

  244. Yi C, Woo JM, Han C, Oh JS, Park I, Lee B, Jin S, Choi H, Kwon JT, Cho BN, Kim DH, Cho C (2010) Expression analysis of the Adam21 gene in mouse testis. Gene Expr Patterns 10(2–3):152–158. https://doi.org/10.1016/j.gep.2010.01.003

    Article  CAS  PubMed  Google Scholar 

  245. Yang P, Baker KA, Hagg T (2005) A disintegrin and metalloprotease 21 (ADAM21) is associated with neurogenesis and axonal growth in developing and adult rodent CNS. J Comp Neurol 490(2):163–179. https://doi.org/10.1002/cne.20659

    Article  CAS  PubMed  Google Scholar 

  246. Cerretti DP, DuBose RF, Black RA, Nelson N (1999) Isolation of two novel metalloproteinase-disintegrin (ADAM) cDNAs that show testis-specific gene expression. Biochem Biophys Res Commun 263(3):810–815. https://doi.org/10.1006/bbrc.1999.1322

    Article  CAS  PubMed  Google Scholar 

  247. Letronne F, Laumet G, Ayral AM, Chapuis J, Demiautte F, Laga M, Vandenberghe ME, Malmanche N, Leroux F, Eysert F, Sottejeau Y, Chami L, Flaig A, Bauer C, Dourlen P, Lesaffre M, Delay C, Huot L, Dumont J, Werkmeister E, Lafont F, Mendes T, Hansmannel F, Dermaut B, Deprez B, Herard AS, Dhenain M, Souedet N, Pasquier F, Tulasne D, Berr C, Hauw JJ, Lemoine Y, Amouyel P, Mann D, Deprez R, Checler F, Hot D, Delzescaux T, Gevaert K, Lambert JC (2016) ADAM30 downregulates APP-linked defects through cathepsin D activation in Alzheimer’s disease. EBioMedicine 9:278–292. https://doi.org/10.1016/j.ebiom.2016.06.002

    Article  PubMed  PubMed Central  Google Scholar 

  248. Vassar R, Kuhn PH, Haass C, Kennedy ME, Rajendran L, Wong PC, Lichtenthaler SF (2014) Function, therapeutic potential and cell biology of BACE proteases: current status and future prospects. J Neurochem 130(1):4–28. https://doi.org/10.1111/jnc.12715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  249. Yoshinaka T, Nishii K, Yamada K, Sawada H, Nishiwaki E, Smith K, Yoshino K, Ishiguro H, Higashiyama S (2002) Identification and characterization of novel mouse and human ADAM33s with potential metalloprotease activity. Gene 282(1–2):227–236

    Article  CAS  Google Scholar 

  250. Cousin H, Abbruzzese G, McCusker C, Alfandari D (2012) ADAM13 function is required in the 3 dimensional context of the embryo during cranial neural crest cell migration in Xenopus laevis. Dev Biol 368(2):335–344. https://doi.org/10.1016/j.ydbio.2012.05.036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  251. Tripathi P, Awasthi S, Gao P (2014) ADAM metallopeptidase domain 33 (ADAM33): a promising target for asthma. Mediat Inflamm 2014:572025. https://doi.org/10.1155/2014/572025

    Article  CAS  Google Scholar 

  252. Van Eerdewegh P, Little RD, Dupuis J, Del Mastro RG, Falls K, Simon J, Torrey D, Pandit S, McKenny J, Braunschweiger K, Walsh A, Liu Z, Hayward B, Folz C, Manning SP, Bawa A, Saracino L, Thackston M, Benchekroun Y, Capparell N, Wang M, Adair R, Feng Y, Dubois J, FitzGerald MG, Huang H, Gibson R, Allen KM, Pedan A, Danzig MR, Umland SP, Egan RW, Cuss FM, Rorke S, Clough JB, Holloway JW, Holgate ST, Keith TP (2002) Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness. Nature 418(6896):426–430. https://doi.org/10.1038/nature00878

    Article  CAS  PubMed  Google Scholar 

  253. Gunn TM, Azarani A, Kim PH, Hyman RW, Davis RW, Barsh GS (2002) Identification and preliminary characterization of mouse Adam33. BMC Genet 3:2

    Article  Google Scholar 

  254. Zou J, Zhu F, Liu J, Wang W, Zhang R, Garlisi CG, Liu YH, Wang S, Shah H, Wan Y, Umland SP (2004) Catalytic activity of human ADAM33. J Biol Chem 279(11):9818–9830. https://doi.org/10.1074/jbc.M309696200

    Article  CAS  PubMed  Google Scholar 

  255. Zou J, Zhang R, Zhu F, Liu J, Madison V, Umland SP (2005) ADAM33 enzyme properties and substrate specificity. Biochemistry 44(11):4247–4256. https://doi.org/10.1021/bi0476230

    Article  CAS  PubMed  Google Scholar 

  256. Alfandari D, Cousin H, Gaultier A, Smith K, White JM, Darribere T, DeSimone DW (2001) Xenopus ADAM 13 is a metalloprotease required for cranial neural crest-cell migration. Curr Biol 11(12):918–930

    Article  CAS  Google Scholar 

  257. Marchant DJ, Bellac CL, Moraes TJ, Wadsworth SJ, Dufour A, Butler GS, Bilawchuk LM, Hendry RG, Robertson AG, Cheung CT, Ng J, Ang L, Luo Z, Heilbron K, Norris MJ, Duan W, Bucyk T, Karpov A, Devel L, Georgiadis D, Hegele RG, Luo H, Granville DJ, Dive V, McManus BM, Overall CM (2014) A new transcriptional role for matrix metalloproteinase-12 in antiviral immunity. Nat Med 20(5):493–502. https://doi.org/10.1038/nm.3508

    Article  CAS  PubMed  Google Scholar 

  258. Huth T, Schmidt-Neuenfeldt K, Rittger A, Saftig P, Reiss K, Alzheimer C (2009) Non-proteolytic effect of beta-site APP-cleaving enzyme 1 (BACE1) on sodium channel function. Neurobiol Dis 33(2):282–289. https://doi.org/10.1016/j.nbd.2008.10.015

    Article  CAS  PubMed  Google Scholar 

  259. Gerst JL, Raina AK, Pirim I, McShea A, Harris PL, Siedlak SL, Takeda A, Petersen RB, Smith MA (2000) Altered cell-matrix associated ADAM proteins in Alzheimer disease. J Neurosci Res 59(5):680–684. https://doi.org/10.1002/(SICI)1097-4547(20000301)59:5%3c680:AID-JNR11%3e3.0.CO;2-6

    Article  CAS  PubMed  Google Scholar 

  260. Murase S, Cho C, White JM, Horwitz AF (2008) ADAM2 promotes migration of neuroblasts in the rostral migratory stream to the olfactory bulb. Eur J Neurosci 27(7):1585–1595. https://doi.org/10.1111/j.1460-9568.2008.06119.x

    Article  PubMed  PubMed Central  Google Scholar 

  261. Wolfsberg TG, Straight PD, Gerena RL, Huovila AP, Primakoff P, Myles DG, White JM (1995) ADAM, a widely distributed and developmentally regulated gene family encoding membrane proteins with a disintegrin and metalloprotease domain. Dev Biol 169(1):378–383. https://doi.org/10.1006/dbio.1995.1152

    Article  CAS  PubMed  Google Scholar 

  262. Cornwall GA, Hsia N (1997) ADAM7, a member of the ADAM (a disintegrin and metalloprotease) gene family is specifically expressed in the mouse anterior pituitary and epididymis. Endocrinology 138(10):4262–4272. https://doi.org/10.1210/endo.138.10.5468

    Article  CAS  PubMed  Google Scholar 

  263. Marcinkiewicz M, Seidah NG (2000) Coordinated expression of beta-amyloid precursor protein and the putative beta-secretase BACE and alpha-secretase ADAM10 in mouse and human brain. J Neurochem 75(5):2133–2143

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the Deutsche Forschungsgemeinschaft (German Research Foundation) within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy) and the research unit FOR2290, by the Centers of Excellence in Neurodegeneration, and the Boehringer Ingelheim Fonds.

Author information

Authors and Affiliations

  1. German Center for Neurodegenerative Diseases (DZNE), Feodor-Lynen Strasse 17, 81377, Munich, Germany

    Hung-En Hsia, Johanna Tüshaus, Tobias Brummer, Yuanpeng Zheng, Simone D. Scilabra & Stefan F. Lichtenthaler

  2. Neuroproteomics, School of Medicine, Klinikum rechts der Isar, and Institute for Advanced Science, Technische Universität München, 81675, Munich, Germany

    Hung-En Hsia, Johanna Tüshaus, Tobias Brummer, Yuanpeng Zheng, Simone D. Scilabra & Stefan F. Lichtenthaler

  3. Fondazione Ri.MED, Department of Research, IRCCS-ISMETT, via Tricomi 5, 90127, Palermo, Italy

    Simone D. Scilabra

  4. Munich Center for Systems Neurology (SyNergy), Munich, Germany

    Stefan F. Lichtenthaler

Authors
  1. Hung-En Hsia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Johanna Tüshaus
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tobias Brummer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuanpeng Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Simone D. Scilabra
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Stefan F. Lichtenthaler
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stefan F. Lichtenthaler.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hsia, HE., Tüshaus, J., Brummer, T. et al. Functions of ‘A disintegrin and metalloproteases (ADAMs)’ in the mammalian nervous system. Cell. Mol. Life Sci. 76, 3055–3081 (2019). https://doi.org/10.1007/s00018-019-03173-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-019-03173-7

Keywords

Search

Navigation