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Adhesion GPCR-Related Protein Networks

  • Barbara Knapp
  • Uwe WolfrumEmail author
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 234)

Graphical Abstract

Abstract

Adhesion G protein-coupled receptors (aGPCRs/ADGRs) are unique receptors that combine cell adhesion and signaling functions. Protein networks related to ADGRs exert diverse functions, e.g., in tissue polarity, cell migration, nerve cell function, or immune response, and are regulated via different mechanisms. The large extracellular domain of ADGRs is capable of mediating cell–cell or cell–matrix protein interactions. Their intracellular surface and domains are coupled to downstream signaling pathways and often bind to scaffold proteins, organizing membrane-associated protein complexes. The cohesive interplay between ADGR-related network components is essential to prevent severe disease-causing damage in numerous cell types. Consequently, in recent years, attention has focused on the decipherment of the precise molecular composition of ADGR protein complexes and interactomes in various cellular modules. In this chapter, we discuss the affiliation of ADGR networks to cellular modules and how they can be regulated, pinpointing common features in the networks related to the diverse ADGRs. Detailed decipherment of the composition of protein networks should provide novel targets for the development of novel therapies with the aim to cure human diseases related to ADGRs.

Keywords

Protein networks Adhesion complexes Adhesion GPCR Affinity proteomics Brain-specific angiogenesis inhibitor Latrophillin VLGR1 GPR98 ADGR Signaling pathways 

Notes

Acknowledgments

We thank Drs. Helen May-Simera and Kerstin Nagel-Wolfrum for critical reading of the manuscript and skillful language corrections. We also thank Dr. Kirsten A. Wunderlich and Fabian Möller for their help. Funding from the following sources is gratefully acknowledged: BMBF “HOPE2” (01GM1108D), DFG FOR 2149 Project 6 (WO54878-1), European Union FP7/2009/241955 (SYSCILIA) and FP7/2009/242013 (TREATRUSH), FAUN-Stiftung, Nuremberg, and the Foundation Fighting Blindness (FFB).

References

  1. 1.
    Hamann J, Aust G, Arac D, Engel FB, Formstone C et al (2015) International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors. Pharmacol Rev 67:338–367PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Krishnan A, Nijmeijer S, de Graaf C, Schiöth HB (2016) Classification, nomenclature and structural aspects of adhesion GPCRs. In: Langenhan T, Schöneberg T (eds) Adhesion G protein-coupled receptors: molecular, physiological and pharmacological principles in health and disease. Springer, HeidelbergGoogle Scholar
  3. 3.
    Arac D, Boucard AA, Bolliger MF, Nguyen J, Soltis SM et al (2012) A novel evolutionarily conserved domain of cell-adhesion GPCRs mediates autoproteolysis. EMBO J 31:1364–1378PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Araç D, Sträter N, Seiradake E (2016) Understanding the structural basis of adhesion GPCR functions. In: Langenhan T, Schöneberg T (eds) Adhesion G protein-coupled receptors: molecular, physiological and pharmacological principles in health and disease. Springer, HeidelbergGoogle Scholar
  5. 5.
    Nieberler M, Kittel RJ, Petrenko AG, Lin H-H, Langenhan T (2016) Control of adhesion GPCR function through proteolytic processing. In: Langenhan T, Schöneberg T (eds) Adhesion G protein-coupled receptors: molecular, physiological and pharmacological principles in health and disease. Springer, HeidelbergGoogle Scholar
  6. 6.
    Luck K, Charbonnier S, Trave G (2012) The emerging contribution of sequence context to the specificity of protein interactions mediated by PDZ domains. FEBS Lett 586:2648–2661PubMedCrossRefGoogle Scholar
  7. 7.
    Dunn HA, Ferguson SS (2015) PDZ protein regulation of G protein-coupled receptor trafficking and signaling pathways. Mol Pharmacol 88:624–639PubMedCrossRefGoogle Scholar
  8. 8.
    Kreienkamp HJ, Zitzer H, Gundelfinger ED, Richter D, Bockers TM (2000) The calcium-independent receptor for alpha-latrotoxin from human and rodent brains interacts with members of the ProSAP/SSTRIP/Shank family of multidomain proteins. J Biol Chem 275:32387–32390PubMedCrossRefGoogle Scholar
  9. 9.
    Tobaben S, Sudhof TC, Stahl B (2000) The G protein-coupled receptor CL1 interacts directly with proteins of the Shank family. J Biol Chem 275:36204–36210PubMedCrossRefGoogle Scholar
  10. 10.
    O’Sullivan ML, de Wit J, Savas JN, Comoletti D, Otto-Hitt S et al (2012) FLRT proteins are endogenous latrophilin ligands and regulate excitatory synapse development. Neuron 73:903–910PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Boucard AA, Ko J, Sudhof TC (2012) High affinity neurexin binding to cell adhesion G-protein-coupled receptor CIRL1/latrophilin-1 produces an intercellular adhesion complex. J Biol Chem 287:9399–9413PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Silva JP, Lelianova VG, Ermolyuk YS, Vysokov N, Hitchen PG et al (2011) Latrophilin 1 and its endogenous ligand Lasso/teneurin-2 form a high-affinity transsynaptic receptor pair with signaling capabilities. Proc Natl Acad Sci U S A 108:12113–12118PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Stacey M, Chang GW, Davies JQ, Kwakkenbos MJ, Sanderson RD et al (2003) The epidermal growth factor-like domains of the human EMR2 receptor mediate cell attachment through chondroitin sulfate glycosaminoglycans. Blood 102:2916–2924PubMedCrossRefGoogle Scholar
  14. 14.
    Hamann J, Vogel B, van Schijndel GM, van Lier RA (1996) The seven-span transmembrane receptor CD97 has a cellular ligand (CD55, DAF). J Exp Med 184:1185–1189PubMedCrossRefGoogle Scholar
  15. 15.
    Wandel E, Saalbach A, Sittig D, Gebhardt C, Aust G (2012) Thy-1 (CD90) is an interacting partner for CD97 on activated endothelial cells. J Immunol 188:1442–1450PubMedCrossRefGoogle Scholar
  16. 16.
    Wang T, Ward Y, Tian L, Lake R, Guedez L et al (2005) CD97, an adhesion receptor on inflammatory cells, stimulates angiogenesis through binding integrin counterreceptors on endothelial cells. Blood 105:2836–2844PubMedCrossRefGoogle Scholar
  17. 17.
    Fernandez E, Collins MO, Uren RT, Kopanitsa MV, Komiyama NH et al (2009) Targeted tandem affinity purification of PSD-95 recovers core postsynaptic complexes and schizophrenia susceptibility proteins. Mol Syst Biol 5:269PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Yamamoto Y, Irie K, Asada M, Mino A, Mandai K et al (2004) Direct binding of the human homologue of the Drosophila disc large tumor suppressor gene to seven-pass transmembrane proteins, tumor endothelial marker 5 (TEM5), and a novel TEM5-like protein. Oncogene 23:3889–3897PubMedCrossRefGoogle Scholar
  19. 19.
    Wu G, Feng X, Stein L (2010) A human functional protein interaction network and its application to cancer data analysis. Genome Biol 11:R53PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Li X, Roszko I, Sepich DS, Ni M, Hamm HE et al (2013) Gpr125 modulates Dishevelled distribution and planar cell polarity signaling. Development 140:3028–3039PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Nishimura T, Honda H, Takeichi M (2012) Planar cell polarity links axes of spatial dynamics in neural-tube closure. Cell 149:1084–1097PubMedCrossRefGoogle Scholar
  22. 22.
    Berndt JD, Aoyagi A, Yang P, Anastas JN, Tang L et al (2011) Mindbomb 1, an E3 ubiquitin ligase, forms a complex with RYK to activate Wnt/beta-catenin signaling. J Cell Biol 194:737–750PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Hermle T, Guida MC, Beck S, Helmstadter S, Simons M (2013) Drosophila ATP6AP2/VhaPRR functions both as a novel planar cell polarity core protein and a regulator of endosomal trafficking. EMBO J 32:245–259PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Nakayama M, Kikuno R, Ohara O (2002) Protein-protein interactions between large proteins: two-hybrid screening using a functionally classified library composed of long cDNAs. Genome Res 12:1773–1784PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Bohnekamp J, Schoneberg T (2011) Cell adhesion receptor GPR133 couples to Gs protein. J Biol Chem 286:41912–41916PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Gupte J, Swaminath G, Danao J, Tian H, Li Y et al (2012) Signaling property study of adhesion G-protein-coupled receptors. FEBS Lett 586:1214–1219PubMedCrossRefGoogle Scholar
  27. 27.
    Tang X, Jin R, Qu G, Wang X, Li Z et al (2013) GPR116, an adhesion G-protein-coupled receptor, promotes breast cancer metastasis via the Galphaq-p63RhoGEF-Rho GTPase pathway. Cancer Res 73:6206–6218PubMedCrossRefGoogle Scholar
  28. 28.
    Fukuzawa T, Ishida J, Kato A, Ichinose T, Ariestanti DM et al (2013) Lung surfactant levels are regulated by Ig-Hepta/GPR116 by monitoring surfactant protein D. PLoS One 8, e69451PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Stephenson JR, Paavola KJ, Schaefer SA, Kaur B, Van Meir EG et al (2013) Brain-specific angiogenesis inhibitor-1 signaling, regulation, and enrichment in the postsynaptic density. J Biol Chem 288:22248–22256PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Stephenson JR, Purcell RH, Hall RA (2014) The BAI subfamily of adhesion GPCRs: synaptic regulation and beyond. Trends Pharmacol Sci 35:208–215PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Park D, Tosello-Trampont AC, Elliott MR, Lu M, Haney LB et al (2007) BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. Nature 450:430–434PubMedCrossRefGoogle Scholar
  32. 32.
    Koh JT, Lee ZH, Ahn KY, Kim JK, Bae CS et al (2001) Characterization of mouse brain-specific angiogenesis inhibitor 1 (BAI1) and phytanoyl-CoA alpha-hydroxylase-associated protein 1, a novel BAI1-binding protein. Brain Res Mol Brain Res 87:223–237PubMedCrossRefGoogle Scholar
  33. 33.
    Kaur B, Cork SM, Sandberg EM, Devi NS, Zhang Z et al (2009) Vasculostatin inhibits intracranial glioma growth and negatively regulates in vivo angiogenesis through a CD36-dependent mechanism. Cancer Res 69:1212–1220PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Duman JG, Tzeng CP, Tu YK, Munjal T, Schwechter B et al (2013) The adhesion-GPCR BAI1 regulates synaptogenesis by controlling the recruitment of the Par3/Tiam1 polarity complex to synaptic sites. J Neurosci 33:6964–6978PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Wu Y, Dowbenko D, Spencer S, Laura R, Lee J et al (2000) Interaction of the tumor suppressor PTEN/MMAC with a PDZ domain of MAGI3, a novel membrane-associated guanylate kinase. J Biol Chem 275:21477–21485PubMedCrossRefGoogle Scholar
  36. 36.
    Koh JT, Kook H, Kee HJ, Seo YW, Jeong BC et al (2004) Extracellular fragment of brain-specific angiogenesis inhibitor 1 suppresses endothelial cell proliferation by blocking alphavbeta5 integrin. Exp Cell Res 294:172–184PubMedCrossRefGoogle Scholar
  37. 37.
    Basei FL, Meirelles GV, Righetto GL, Dos Santos Migueleti DL, Smetana JH et al (2015) New interaction partners for Nek4.1 and Nek4.2 isoforms: from the DNA damage response to RNA splicing. Proteome Sci 13:11PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Cork SM, Kaur B, Devi NS, Cooper L, Saltz JH et al (2012) A proprotein convertase/MMP-14 proteolytic cascade releases a novel 40 kDa vasculostatin from tumor suppressor BAI1. Oncogene 31:5144–5152PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Lim IA, Hall DD, Hell JW (2002) Selectivity and promiscuity of the first and second PDZ domains of PSD-95 and synapse-associated protein 102. J Biol Chem 277:21697–21711PubMedCrossRefGoogle Scholar
  40. 40.
    Shiratsuchi A, Osada S, Kanazawa S, Nakanishi Y (1998) Essential role of phosphatidylserine externalization in apoptosing cell phagocytosis by macrophages. Biochem Biophys Res Commun 246:549–555PubMedCrossRefGoogle Scholar
  41. 41.
    Shiratsuchi T, Futamura M, Oda K, Nishimori H, Nakamura Y et al (1998) Cloning and characterization of BAI-associated protein 1: a PDZ domain-containing protein that interacts with BAI1. Biochem Biophys Res Commun 247:597–604PubMedCrossRefGoogle Scholar
  42. 42.
    Oda K, Shiratsuchi T, Nishimori H, Inazawa J, Yoshikawa H et al (1999) Identification of BAIAP2 (BAI-associated protein 2), a novel human homologue of hamster IRSp53, whose SH3 domain interacts with the cytoplasmic domain of BAI1. Cytogenet Cell Genet 84:75–82PubMedCrossRefGoogle Scholar
  43. 43.
    Jeong BC, Kim MY, Lee JH, Kee HJ, Kho DH et al (2006) Brain-specific angiogenesis inhibitor 2 regulates VEGF through GABP that acts as a transcriptional repressor. FEBS Lett 580:669–676PubMedCrossRefGoogle Scholar
  44. 44.
    Petersen HH, Hilpert J, Militz D, Zandler V, Jacobsen C et al (2003) Functional interaction of megalin with the megalin-binding protein (MegBP), a novel tetratrico peptide repeat-containing adaptor molecule. J Cell Sci 116:453–461PubMedCrossRefGoogle Scholar
  45. 45.
    Hamoud N, Tran V, Croteau LP, Kania A, Cote JF (2014) G-protein coupled receptor BAI3 promotes myoblast fusion in vertebrates. Proc Natl Acad Sci U S A 111(10):3745–3750PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Bolliger MF, Martinelli DC, Sudhof TC (2011) The cell-adhesion G protein-coupled receptor BAI3 is a high-affinity receptor for C1q-like proteins. Proc Natl Acad Sci U S A 108:2534–2539PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Luo R, Jeong SJ, Jin Z, Strokes N, Li S, Piao X (2011) G protein-coupled receptor 56 and collagen III, a receptor-ligand pair, regulates cortical development and lamination. Proc Natl Acad Sci U S A 108(31):12925–12930. doi: 10.1073/pnas.1104821108, PubMed PMID: 21768377, PubMed Central PMCID: PMC3150909, Epub 2011/07/20PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Paavola KJ, Stephenson JR, Ritter SL, Alter SP, Hall RA (2011) The N terminus of the adhesion G protein-coupled receptor GPR56 controls receptor signaling activity. J Biol Chem 286:28914–28921PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Xu L, Begum S, Hearn JD, Hynes RO (2006) GPR56, an atypical G protein-coupled receptor, binds tissue transglutaminase, TG2, and inhibits melanoma tumor growth and metastasis. Proc Natl Acad Sci U S A 103:9023–9028PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Little KD, Hemler ME, Stipp CS (2004) Dynamic regulation of a GPCR-tetraspanin-G protein complex on intact cells: central role of CD81 in facilitating GPR56-Galpha q/11 association. Mol Biol Cell 15:2375–2387PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Iguchi T, Sakata K, Yoshizaki K, Tago K, Mizuno N et al (2008) Orphan G protein-coupled receptor GPR56 regulates neural progenitor cell migration via a G alpha 12/13 and Rho pathway. J Biol Chem 283:14469–14478PubMedCrossRefGoogle Scholar
  52. 52.
    Peeters MC, Fokkelman M, Boogaard B, Egerod KL, van de Water B et al (2015) The adhesion G protein-coupled receptor G2 (ADGRG2/GPR64) constitutively activates SRE and NFkappaB and is involved in cell adhesion and migration. Cell Signal 27:2579–2588PubMedCrossRefGoogle Scholar
  53. 53.
    Valtcheva N, Primorac A, Jurisic G, Hollmen M, Detmar M (2013) The orphan adhesion G protein-coupled receptor GPR97 regulates migration of lymphatic endothelial cells via the small GTPases RhoA and Cdc42. J Biol Chem 288:35736–35748PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Monk KR, Naylor SG, Glenn TD, Mercurio S, Perlin JR et al (2009) A G protein-coupled receptor is essential for Schwann cells to initiate myelination. Science 325:1402–1405PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Paavola KJ, Sidik H, Zuchero JB, Eckart M, Talbot WS (2014) Type IV collagen is an activating ligand for the adhesion G protein-coupled receptor GPR126. Sci Signal 7:ra76PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Mogha A, Benesh AE, Patra C, Engel FB, Schoneberg T et al (2013) Gpr126 functions in Schwann cells to control differentiation and myelination via G-protein activation. J Neurosci 33:17976–17985PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Petersen SC, Luo R, Liebscher I, Giera S, Jeong SJ et al (2015) The adhesion GPCR GPR126 has distinct, domain-dependent functions in Schwann cell development mediated by interaction with laminin-211. Neuron 85:755–769PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Zallocchi M, Delimont D, Meehan DT, Cosgrove D (2012) Regulated vesicular trafficking of specific PCDH15 and VLGR1 variants in auditory hair cells. J Neurosci 32:13841–13859PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Shin D, Lin ST, Fu YH, Ptacek LJ (2013) Very large G protein-coupled receptor 1 regulates myelin-associated glycoprotein via Galphas/Galphaq-mediated protein kinases A/C. Proc Natl Acad Sci U S A 110:19101–19106PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Reiners J, van Wijk E, Marker T, Zimmermann U, Jurgens K et al (2005) Scaffold protein harmonin (USH1C) provides molecular links between Usher syndrome type 1 and type 2. Hum Mol Genet 14:3933–3943PubMedCrossRefGoogle Scholar
  61. 61.
    van Wijk E, van der Zwaag B, Peters T, Zimmermann U, te Brinke H et al (2006) The DFNB31 gene product whirlin connects to the Usher protein network in the cochlea and retina by direct association with USH2A and VLGR1. Hum Mol Genet 15:751–765PubMedCrossRefGoogle Scholar
  62. 62.
    Michalski N, Michel V, Bahloul A, Lefevre G, Barral J et al (2007) Molecular characterization of the ankle-link complex in cochlear hair cells and its role in the hair bundle functioning. J Neurosci 27:6478–6488PubMedCrossRefGoogle Scholar
  63. 63.
    Ebermann I, Phillips JB, Liebau MC, Koenekoop RK, Schermer B et al (2010) PDZD7 is a modifier of retinal disease and a contributor to digenic Usher syndrome. J Clin Invest 120:1812–1823PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Hu QX, Dong JH, Du HB, Zhang DL, Ren HZ et al (2014) Constitutive Galphai coupling activity of very large G protein-coupled receptor 1 (VLGR1) and its regulation by PDZD7 protein. J Biol Chem 289:24215–24225PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Das G, Reynolds-Kenneally J, Mlodzik M (2002) The atypical cadherin Flamingo links Frizzled and Notch signaling in planar polarity establishment in the Drosophila eye. Dev Cell 2:655–666PubMedCrossRefGoogle Scholar
  66. 66.
    Rawls AS, Wolff T (2003) Strabismus requires Flamingo and Prickle function to regulate tissue polarity in the Drosophila eye. Development 130:1877–1887PubMedCrossRefGoogle Scholar
  67. 67.
    Muller A, Winkler J, Fiedler F, Sastradihardja T, Binder C, Schnabel R et al (2015) Oriented cell division in the C. elegans embryo is coordinated by G-protein signaling dependent on the adhesion GPCR LAT-1. PLoS Genet 11(10), e1005624PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Krasnoperov VG, Bittner MA, Beavis R, Kuang Y, Salnikow KV et al (1997) Alpha-Latrotoxin stimulates exocytosis by the interaction with a neuronal G-protein-coupled receptor. Neuron 18:925–937PubMedCrossRefGoogle Scholar
  69. 69.
    Lelianova VG, Davletov BA, Sterling A, Rahman MA, Grishin EV et al (1997) Alpha-latrotoxin receptor, latrophilin, is a novel member of the secretin family of G protein-coupled receptors. J Biol Chem 272:21504–21508PubMedCrossRefGoogle Scholar
  70. 70.
    Sugita S, Ichtchenko K, Khvotchev M, Sudhof TC (1998) Alpha-Latrotoxin receptor CIRL/latrophilin 1 (CL1) defines an unusual family of ubiquitous G-protein-linked receptors. G-protein coupling not required for triggering exocytosis. J Biol Chem 273:32715–32724PubMedCrossRefGoogle Scholar
  71. 71.
    Tabuchi K, Sudhof TC (2002) Structure and evolution of neurexin genes: insight into the mechanism of alternative splicing. Genomics 79:849–859PubMedCrossRefGoogle Scholar
  72. 72.
    Woelfle R, D’Aquila AL, Pavlovic T, Husic M, Lovejoy DA (2015) Ancient interaction between the teneurin C-terminal associated peptides (TCAP) and latrophilin ligand-receptor coupling: a role in behavior. Front Neurosci 9:146PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Sugita S (2001) A stoichiometric complex of neurexins and dystroglycan in brain. J Cell Biol 154:435–446PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Trzebiatowska A, Topf U, Sauder U, Drabikowski K, Chiquet-Ehrismann R (2008) Caenorhabditis elegans teneurin, -1, is required for gonadal and pharyngeal basement membrane integrity and acts redundantly with integrin ina-1 and dystroglycan dgn-1. Mol Biol Cell 19:3898–3908PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Chand D, Colacci M, Dixon K, Kollara A, Brown TJ et al (2014) C-terminal region of teneurin-1 co-localizes with the dystroglycan complex in adult mouse testes and regulates testicular size and testosterone production. Histochem Cell Biol 141:191–211PubMedCrossRefGoogle Scholar
  76. 76.
    Banks GB, Fuhrer C, Adams ME, Froehner SC (2003) The postsynaptic submembrane machinery at the neuromuscular junction: requirement for rapsyn and the utrophin/dystrophin-associated complex. J Neurocytol 32:709–726PubMedCrossRefGoogle Scholar
  77. 77.
    Masaki T, Matsumura K (2010) Biological role of dystroglycan in Schwann cell function and its implications in peripheral nervous system diseases. J Biomed Biotechnol 2010:740403PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Leyva-Diaz E, del Toro D, Menal MJ, Cambray S, Susin R et al (2014) FLRT3 is a Robo1-interacting protein that determines Netrin-1 attraction in developing axons. Curr Biol 24:494–508PubMedCrossRefGoogle Scholar
  79. 79.
    Feng W, Zhang M (2009) Organization and dynamics of PDZ-domain-related supramodules in the postsynaptic density. Nat Rev Neurosci 10:87–99PubMedCrossRefGoogle Scholar
  80. 80.
    Kim E, Sheng M (2004) PDZ domain proteins of synapses. Nat Rev Neurosci 5:771–781PubMedCrossRefGoogle Scholar
  81. 81.
    Yamanaka T, Ohno S (2008) Role of Lgl/Dlg/Scribble in the regulation of epithelial junction, polarity and growth. Front Biosci 13:6693–6707PubMedCrossRefGoogle Scholar
  82. 82.
    Mori K, Kanemura Y, Fujikawa H, Nakano A, Ikemoto H et al (2002) Brain-specific angiogenesis inhibitor 1 (BAI1) is expressed in human cerebral neuronal cells. Neurosci Res 43:69–74PubMedCrossRefGoogle Scholar
  83. 83.
    Sokolowski JD, Nobles SL, Heffron DS, Park D, Ravichandran KS et al (2011) Brain-specific angiogenesis inhibitor-1 expression in astrocytes and neurons: implications for its dual function as an apoptotic engulfment receptor. Brain Behav Immun 25:915–921PubMedCrossRefGoogle Scholar
  84. 84.
    Park D, Ravichandran KS (2010) Emerging roles of brain-specific angiogenesis inhibitor 1. Adv Exp Med Biol 706:167–178PubMedCrossRefGoogle Scholar
  85. 85.
    Kaur B, Brat DJ, Devi NS, Van Meir EG (2005) Vasculostatin, a proteolytic fragment of brain angiogenesis inhibitor 1, is an antiangiogenic and antitumorigenic factor. Oncogene 24:3632–3642PubMedCrossRefGoogle Scholar
  86. 86.
    Adams JC, Tucker RP (2000) The thrombospondin type 1 repeat (TSR) superfamily: diverse proteins with related roles in neuronal development. Dev Dyn 218:280–299PubMedCrossRefGoogle Scholar
  87. 87.
    Duman JG, Mulherkar S, Tu YK, X Cheng J, Tolias KF (2015) Mechanisms for spatiotemporal regulation of Rho-GTPase signaling at synapses. Neurosci Lett 601:4–10PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Das S, Owen KA, Ly KT, Park D, Black SG et al (2011) Brain angiogenesis inhibitor 1 (BAI1) is a pattern recognition receptor that mediates macrophage binding and engulfment of Gram-negative bacteria. Proc Natl Acad Sci U S A 108:2136–2141PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Hochreiter-Hufford AE, Lee CS, Kinchen JM, Sokolowski JD, Arandjelovic S et al (2013) Phosphatidylserine receptor BAI1 and apoptotic cells as new promoters of myoblast fusion. Nature 497:263–267PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Ressl S, Vu BK, Vivona S, Martinelli DC, Sudhof TC et al (2015) Structures of C1q-like proteins reveal unique features among the C1q/TNF superfamily. Structure 23:688–699PubMedCrossRefGoogle Scholar
  91. 91.
    Berube NG, Swanson XH, Bertram MJ, Kittle JD, Didenko V et al (1999) Cloning and characterization of CRF, a novel C1q-related factor, expressed in areas of the brain involved in motor function. Brain Res Mol Brain Res 63:233–240PubMedCrossRefGoogle Scholar
  92. 92.
    Iijima T, Miura E, Watanabe M, Yuzaki M (2010) Distinct expression of C1q-like family mRNAs in mouse brain and biochemical characterization of their encoded proteins. Eur J Neurosci 31:1606–1615PubMedGoogle Scholar
  93. 93.
    Sigoillot SM, Iyer K, Binda F, Gonzalez-Calvo I, Talleur M, et al (2015) The secreted protein C1QL1 and its receptor BAI3 control the synaptic connectivity of excitatory inputs converging on cerebellar Purkinje cells. Cell Rep. pii: S2211-1247(15)00059-5Google Scholar
  94. 94.
    Okajima D, Kudo G, Yokota H (2011) Antidepressant-like behavior in brain-specific angiogenesis inhibitor 2-deficient mice. J Physiol Sci 61:47–54PubMedCrossRefGoogle Scholar
  95. 95.
    Okajima D, Kudo G, Yokota H (2010) Brain-specific angiogenesis inhibitor 2 (BAI2) may be activated by proteolytic processing. J Recept Signal Transduct Res 30:143–153PubMedCrossRefGoogle Scholar
  96. 96.
    McMillan DR, White PC, Grati M, Shin JB, Weston MD et al (2010) Studies on the very large G protein-coupled receptor: from initial discovery to determining its role in sensorineural deafness in higher animals. Adv Exp Med Biol 706:76–86PubMedCrossRefGoogle Scholar
  97. 97.
    Nikkila H, McMillan DR, Nunez BS, Pascoe L, Curnow KM et al (2000) Sequence similarities between a novel putative G protein-coupled receptor and Na+/Ca2+ exchangers define a cation binding domain. Mol Endocrinol 14:1351–1364PubMedCrossRefGoogle Scholar
  98. 98.
    Skradski SL, Clark AM, Jiang H, White HS, Fu YH et al (2001) A novel gene causing a mendelian audiogenic mouse epilepsy. Neuron 31:537–544PubMedCrossRefGoogle Scholar
  99. 99.
    McMillan DR, Kayes-Wandover KM, Richardson JA, White PC (2002) Very large G protein-coupled receptor-1, the largest known cell surface protein, is highly expressed in the developing central nervous system. J Biol Chem 277:785–792PubMedCrossRefGoogle Scholar
  100. 100.
    Weston MD, Luijendijk MW, Humphrey KD, Moller C, Kimberling WJ (2004) Mutations in the VLGR1 gene implicate G-protein signaling in the pathogenesis of Usher syndrome type II. Am J Hum Genet 74:357–366PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Reiners J, Nagel-Wolfrum K, Jurgens K, Märker T, Wolfrum U (2006) Molecular basis of human Usher syndrome: deciphering the meshes of the Usher protein network provides insights into the pathomechanisms of the Usher disease. Exp Eye Res 83:97–119PubMedCrossRefGoogle Scholar
  102. 102.
    Mathur P, Yang J (1852) Usher syndrome: hearing loss, retinal degeneration and associated abnormalities. Biochim Biophys Acta 2015:406–420Google Scholar
  103. 103.
    Jansen F, Kalbe B, Scholz P, Mikosz M, Wunderlich KA et al (2016) Impact of the Usher syndrome on olfaction. Hum Mol Genet 25(3):524–533PubMedCrossRefGoogle Scholar
  104. 104.
    Specht D, Wu SB, Turner P, Dearden P, Koentgen F et al (2009) Effects of presynaptic mutations on a postsynaptic Cacna1s calcium channel colocalized with mGluR6 at mouse photoreceptor ribbon synapses. Invest Ophthalmol Vis Sci 50:505–515PubMedCrossRefGoogle Scholar
  105. 105.
    Gregory FD, Bryan KE, Pangrsic T, Calin-Jageman IE, Moser T et al (2011) Harmonin inhibits presynaptic Cav1.3 Ca(2)(+) channels in mouse inner hair cells. Nat Neurosci 14:1109–1111PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    McGee J, Goodyear RJ, McMillan DR, Stauffer EA, Holt JR et al (2006) The very large G-protein-coupled receptor VLGR1: a component of the ankle link complex required for the normal development of auditory hair bundles. J Neurosci 26:6543–6553PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Lefevre G, Michel V, Weil D, Lepelletier L, Bizard E et al (2008) A core cochlear phenotype in USH1 mouse mutants implicates fibrous links of the hair bundle in its cohesion, orientation and differential growth. Development 135:1427–1437PubMedCrossRefGoogle Scholar
  108. 108.
    Yang J, Liu X, Zhao Y, Adamian M, Pawlyk B et al (2010) Ablation of whirlin long isoform disrupts the USH2 protein complex and causes vision and hearing loss. PLoS Genet 6, e1000955PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Grati M, Shin JB, Weston MD, Green J, Bhat MA et al (2012) Localization of PDZD7 to the stereocilia ankle-link associates this scaffolding protein with the Usher syndrome protein network. J Neurosci 32:14288–14293PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Schneider E, Marker T, Daser A, Frey-Mahn G, Beyer V et al (2009) Homozygous disruption of PDZD7 by reciprocal translocation in a consanguineous family: a new member of the Usher syndrome protein interactome causing congenital hearing impairment. Hum Mol Genet 18:655–666PubMedCrossRefGoogle Scholar
  111. 111.
    Maerker T, van Wijk E, Overlack N, Kersten FF, McGee J et al (2008) A novel Usher protein network at the periciliary reloading point between molecular transport machineries in vertebrate photoreceptor cells. Hum Mol Genet 17:71–86PubMedCrossRefGoogle Scholar
  112. 112.
    Sorusch N, Wunderlich K, Bauá K, Nagel-Wolfrum K, Wolfrum U (2014) Usher syndrome protein network functions in the retina and their relation to other retinal ciliopathies. In: Ash J, Hollyfield JG, LaVail MM, Anderson RE, Grimm C et al (eds) Retinal degenerative diseases. Springer, New York, NYGoogle Scholar
  113. 113.
    Bauss K, Knapp B, Jores P, Roepman R, Kremer H et al (2014) Phosphorylation of the Usher syndrome 1G protein SANS controls Magi2-mediated endocytosis. Hum Mol Genet 23:3923–3942PubMedCrossRefGoogle Scholar
  114. 114.
    Ward Y, Lake R, Yin JJ, Heger CD, Raffeld M et al (2011) LPA receptor heterodimerizes with CD97 to amplify LPA-initiated RHO-dependent signaling and invasion in prostate cancer cells. Cancer Res 71:7301–7311PubMedCrossRefGoogle Scholar
  115. 115.
    Keeble TR, Halford MM, Seaman C, Kee N, Macheda M et al (2006) The Wnt receptor Ryk is required for Wnt5a-mediated axon guidance on the contralateral side of the corpus callosum. J Neurosci 26:5840–5848PubMedCrossRefGoogle Scholar
  116. 116.
    Posokhova E, Shukla A, Seaman S, Volate S, Hilton MB et al (2015) GPR124 functions as a WNT7-specific coactivator of canonical beta-catenin signaling. Cell Rep 10:123–130PubMedCrossRefGoogle Scholar
  117. 117.
    Feng J, Han Q, Zhou L (2012) Planar cell polarity genes, Celsr1-3, in neural development. Neurosci Bull 28:309–315PubMedCrossRefGoogle Scholar
  118. 118.
    Devenport D, Fuchs E (2008) Planar polarization in embryonic epidermis orchestrates global asymmetric morphogenesis of hair follicles. Nat Cell Biol 10:1257–1268PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Ihara S, Oka T, Fukui Y (2006) Direct binding of SWAP-70 to non-muscle actin is required for membrane ruffling. J Cell Sci 119:500–507PubMedCrossRefGoogle Scholar
  120. 120.
    Ferrier A, Boyer JG, Kothary R (2013) Cellular and molecular biology of neuronal dystonin. Int Rev Cell Mol Biol 300:85–120PubMedCrossRefGoogle Scholar
  121. 121.
    Southern C, Cook JM, Neetoo-Isseljee Z, Taylor DL, Kettleborough CA et al (2013) Screening beta-arrestin recruitment for the identification of natural ligands for orphan G-protein-coupled receptors. J Biomol Screen 18:599–609PubMedCrossRefGoogle Scholar
  122. 122.
    Dyer MD, Neff C, Dufford M, Rivera CG, Shattuck D et al (2010) The human-bacterial pathogen protein interaction networks of Bacillus anthracis, Francisella tularensis, and Yersinia pestis. PLoS One 5, e12089PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Hein MY, Hubner NC, Poser I, Cox J, Nagaraj N et al (2015) A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 163:712–723PubMedCrossRefGoogle Scholar
  124. 124.
    Liebscher I, Schöneberg T (2016) Tethered agonism: a common activation mechanism of adhesion GPCRs. In: Langenhan T, Schöneberg T (eds) Adhesion G protein-coupled receptors: molecular, physiological and pharmacological principles in health and disease. Springer, HeidelbergGoogle Scholar
  125. 125.
    Kishore A, Hall RA (2016) Versatile signaling activity of adhesion GPCRs. In: Langenhan T, Schöneberg T (eds) Adhesion G protein-coupled receptors: molecular, physiological and pharmacological principles in health and disease. Springer, HeidelbergGoogle Scholar
  126. 126.
    Kovacs P, Schöneberg T (2016) The relevance of genomic signatures at adhesion GPCR loci in humans. In: Langenhan T, Schöneberg T (eds) Adhesion G protein-coupled receptors: molecular, physiological and pharmacological principles in health and disease. Springer, HeidelbergGoogle Scholar
  127. 127.
    Wolfrum U (2011) Protein networks related to the Usher syndrome gain insights in the molecular basis of the disease. In: Satpal A (ed) Usher syndrome: pathogenesis, diagnosis and therapy. Nova Science, New York, NY, pp 51–73Google Scholar
  128. 128.
    Scheel H, Tomiuk S, Hofmann K (2002) A common protein interaction domain links two recently identified epilepsy genes. Hum Mol Genet 11:1757–1762PubMedCrossRefGoogle Scholar
  129. 129.
    Piao X, Hill RS, Bodell A, Chang BS, Basel-Vanagaite L et al (2004) G protein-coupled receptor-dependent development of human frontal cortex. Science 303:2033–2036PubMedCrossRefGoogle Scholar
  130. 130.
    Piao X, Chang BS, Bodell A, Woods K, Benzeev B et al (2005) Genotype-phenotype analysis of human frontoparietal polymicrogyria syndromes. Ann Neurol 58:680–687PubMedCrossRefGoogle Scholar
  131. 131.
    Piao X, Basel-Vanagaite L, Straussberg R, Grant PE, Pugh EW et al (2002) An autosomal recessive form of bilateral frontoparietal polymicrogyria maps to chromosome 16q12.2-21. Am J Hum Genet 70:1028–1033PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    Chang BS, Piao X, Bodell A, Basel-Vanagaite L, Straussberg R et al (2003) Bilateral frontoparietal polymicrogyria: clinical and radiological features in 10 families with linkage to chromosome 16. Ann Neurol 53:596–606PubMedCrossRefGoogle Scholar
  133. 133.
    Li S, Jin Z, Koirala S, Bu L, Xu L et al (2008) GPR56 regulates pial basement membrane integrity and cortical lamination. J Neurosci 28:5817–5826PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.
    Bahi-Buisson N, Poirier K, Boddaert N, Fallet-Bianco C, Specchio N et al (2010) GPR56-related bilateral frontoparietal polymicrogyria: further evidence for an overlap with the cobblestone complex. Brain 133:3194–3209PubMedCrossRefGoogle Scholar
  135. 135.
    Jeong SJ, Luo R, Li S, Strokes N, Piao X (2012) Characterization of G protein-coupled receptor 56 protein expression in the mouse developing neocortex. J Comp Neurol 520:2930–2940PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Choi J, Ko J, Racz B, Burette A, Lee JR et al (2005) Regulation of dendritic spine morphogenesis by insulin receptor substrate 53, a downstream effector of Rac1 and Cdc42 small GTPases. J Neurosci 25:869–879PubMedCrossRefGoogle Scholar
  137. 137.
    Toma C, Hervas A, Balmana N, Vilella E, Aguilera F et al (2011) Association study of six candidate genes asymmetrically expressed in the two cerebral hemispheres suggests the involvement of BAIAP2 in autism. J Psychiatr Res 45:280–282PubMedCrossRefGoogle Scholar
  138. 138.
    Michaelson JJ, Shi Y, Gujral M, Zheng H, Malhotra D et al (2012) Whole-genome sequencing in autism identifies hot spots for de novo germline mutation. Cell 151:1431–1442PubMedPubMedCentralCrossRefGoogle Scholar
  139. 139.
    Tsai NP, Wilkerson JR, Guo W, Maksimova MA, DeMartino GN et al (2012) Multiple autism-linked genes mediate synapse elimination via proteasomal degradation of a synaptic scaffold PSD-95. Cell 151:1581–1594PubMedPubMedCentralCrossRefGoogle Scholar
  140. 140.
    Liu QR, Drgon T, Johnson C, Walther D, Hess J et al (2006) Addiction molecular genetics: 639,401 SNP whole genome association identifies many “cell adhesion” genes. Am J Med Genet B Neuropsychiatr Genet 141B:918–925PubMedCrossRefGoogle Scholar
  141. 141.
    DeRosse P, Lencz T, Burdick KE, Siris SG, Kane JM et al (2008) The genetics of symptom-based phenotypes: toward a molecular classification of schizophrenia. Schizophr Bull 34:1047–1053PubMedPubMedCentralCrossRefGoogle Scholar
  142. 142.
    Bonaglia MC, Marelli S, Novara F, Commodaro S, Borgatti R et al (2010) Genotype-phenotype relationship in three cases with overlapping 19p13.12 microdeletions. Eur J Hum Genet 18:1302–1309PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Arcos-Burgos M, Muenke M (2010) Toward a better understanding of ADHD: LPHN3 gene variants and the susceptibility to develop ADHD. Atten Defic Hyperact Disord 2:139–147PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    Zweier C, de Jong EK, Zweier M, Orrico A, Ousager LB et al (2009) CNTNAP2 and NRXN1 are mutated in autosomal-recessive Pitt-Hopkins-like mental retardation and determine the level of a common synaptic protein in Drosophila. Am J Hum Genet 85:655–666PubMedPubMedCentralCrossRefGoogle Scholar
  145. 145.
    Sudhof TC (2008) Neuroligins and neurexins link synaptic function to cognitive disease. Nature 455:903–911PubMedPubMedCentralCrossRefGoogle Scholar
  146. 146.
    Allache R, De Marco P, Merello E, Capra V, Kibar Z (2012) Role of the planar cell polarity gene CELSR1 in neural tube defects and caudal agenesis. Birth Defects Res A Clin Mol Teratol 94:176–181PubMedCrossRefGoogle Scholar
  147. 147.
    Robinson A, Escuin S, Doudney K, Vekemans M, Stevenson RE et al (2012) Mutations in the planar cell polarity genes CELSR1 and SCRIB are associated with the severe neural tube defect craniorachischisis. Hum Mutat 33:440–447PubMedCrossRefGoogle Scholar
  148. 148.
    Tissir F, Qu Y, Montcouquiol M, Zhou L, Komatsu K et al (2010) Lack of cadherins Celsr2 and Celsr3 impairs ependymal ciliogenesis, leading to fatal hydrocephalus. Nat Neurosci 13:700–707PubMedCrossRefGoogle Scholar
  149. 149.
    Aust G, Eichler W, Laue S, Lehmann I, Heldin NE et al (1997) CD97: a dedifferentiation marker in human thyroid carcinomas. Cancer Res 57:1798–1806PubMedGoogle Scholar
  150. 150.
    Steinert M, Wobus M, Boltze C, Schütz A, Wahlbuhl M et al (2002) Expression and regulation of CD97 in colorectal carcinoma cell lines and tumor tissues. Am J Pathol 161:1657–1667PubMedPubMedCentralCrossRefGoogle Scholar
  151. 151.
    Galle J, Sittig D, Hanisch I, Wobus M, Wandel E et al (2006) Individual cell-based models of tumor-environment interactions: multiple effects of CD97 on tumor invasion. Am J Pathol 169:1802–1811PubMedPubMedCentralCrossRefGoogle Scholar
  152. 152.
    Zendman AJ, Cornelissen IM, Weidle UH, Ruiter DJ, van Muijen GN (1999) TM7XN1, a novel human EGF-TM7-like cDNA, detected with mRNA differential display using human melanoma cell lines with different metastatic potential. FEBS Lett 446:292–298PubMedCrossRefGoogle Scholar
  153. 153.
    Kaur B, Brat DJ, Calkins CC, Van Meir EG (2003) Brain angiogenesis inhibitor 1 is differentially expressed in normal brain and glioblastoma independently of p53 expression. Am J Pathol 162:19–27PubMedPubMedCentralCrossRefGoogle Scholar
  154. 154.
    Fukushima Y, Oshika Y, Tsuchida T, Tokunaga T, Hatanaka H et al (1998) Brain-specific angiogenesis inhibitor 1 expression is inversely correlated with vascularity and distant metastasis of colorectal cancer. Int J Oncol 13:967–970PubMedGoogle Scholar
  155. 155.
    Zohrabian VM, Nandu H, Gulati N, Khitrov G, Zhao C et al (2007) Gene expression profiling of metastatic brain cancer. Oncol Rep 18:321–328PubMedGoogle Scholar
  156. 156.
    Paavola KJ, Hall RA (2012) Adhesion G protein-coupled receptors: signaling, pharmacology, and mechanisms of activation. Mol Pharmacol 82(5):777–783. doi: 10.1124/mol.112.080309, PubMed PMID: 22821233, PubMed Central PMCID: PMC3477231, Epub 2012/07/24PubMedPubMedCentralCrossRefGoogle Scholar
  157. 157.
    Langenhan T, Promel S, Mestek L, Esmaeili B, Waller-Evans H et al (2009) Latrophilin signaling links anterior-posterior tissue polarity and oriented cell divisions in the C. elegans embryo. Dev Cell 17:494–504PubMedPubMedCentralCrossRefGoogle Scholar
  158. 158.
    Tissir F, Goffinet AM (2013) Atypical cadherins Celsr1-3 and planar cell polarity in vertebrates. Prog Mol Biol Transl Sci 116:193–214PubMedCrossRefGoogle Scholar
  159. 159.
    Na CH, Jones DR, Yang Y, Wang X, Xu Y et al (2012) Synaptic protein ubiquitination in rat brain revealed by antibody-based ubiquitome analysis. J Proteome Res 11:4722–4732PubMedPubMedCentralCrossRefGoogle Scholar
  160. 160.
    Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD et al (2012) Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition. Mol Cell Proteomics 11:148–159PubMedPubMedCentralCrossRefGoogle Scholar
  161. 161.
    Lin AW, Man HY (2013) Ubiquitination of neurotransmitter receptors and postsynaptic scaffolding proteins. Neural Plast 2013:432057PubMedPubMedCentralGoogle Scholar
  162. 162.
    Huangfu WC, Fuchs SY (2010) Ubiquitination-dependent regulation of signaling receptors in cancer. Genes Cancer 1:725–734PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2016

Authors and Affiliations

  1. 1.Cell and Matrix BiologyInstitute of Zoology, Johannes Gutenberg University of MainzMainzGermany

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