Abstract
The sortilin family of Vps10p-domain receptors includes sortilin, SorLA, and SorCS1–3. These type-I transmembrane receptors predominate in distinct neuronal tissues, but expression is also present in certain specialized non-neuronal cell populations including hepatocytes and cells of the immune system. The biology of sortilins is complex as they participate in both cell signaling and in intracellular protein sorting. Sortilins function physiologically in signaling by pro- and mature neurotrophins in neuronal viability and functionality. Recent genome-wide association studies have linked members to neurological disorders such as Alzheimer’s disease and bipolar disorder and outside the nervous system to development of coronary artery disease and type-2 diabetes. Particularly well described are the receptor functions in neuronal signaling by pro- (proNT) and mature (NT) neurotrophins and in the processing/metabolism of amyloid precursor protein (APP).
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Adler R, Landa KB, Manthorpe M, Varon S (1979) Cholinergic neuronotrophic factors: intraocular distribution of trophic activity for ciliary neurons. Science 204(4400):1434–1436
Ahmed Z, Sheng H, Xu YF, Lin WL, Innes AE, Gass J, Yu X, Wuertzer CA, Hou H, Chiba S, Yamanouchi K, Leissring M, Petrucelli L, Nishihara M, Hutton ML, McGowan E, Dickson DW, Lewis J (2010) Accelerated lipofuscinosis and ubiquitination in granulin knockout mice suggest a role for progranulin in successful aging. Am J Pathol 177(1):311–324
Al-Shawi R, Hafner A, Olsen J, Chun S, Raza S, Thrasivoulou C, Lovestone S, Killick R, Simons P, Cowen T (2008) Neurotoxic and neurotrophic roles of proNGF and the receptor sortilin in the adult and ageing nervous system. Eur J Neurosci 27(8):2103–2114
Andersen OM, Reiche J, Schmidt V, Gotthardt M, Spoelgen R, Behlke J, von Arnim CA, Breiderhoff T, Jansen P, Wu X, Bales KR, Cappai R, Masters CL, Gliemann J, Mufson EJ, Hyman BT, Paul SM, Nykjaer A, Willnow TE (2005) Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein. Proc Natl Acad Sci U S A 102(38):13461–13466
Bamji SX, Majdan M, Pozniak CD, Belliveau DJ, Aloyz R, Kohn J, Causing CG, Miller FD (1998) The p75 neurotrophin receptor mediates neuronal apoptosis and is essential for naturally occurring sympathetic neuron death. J Cell Biol 140(4):911–923
Bateman A, Bennett HP (2009) The granulin gene family: from cancer to dementia. Bioessays 31(11):1245–1254
Baum AE, Akula N, Cabanero M, Cardona I, Corona W, Klemens B, Schulze TG, Cichon S, Rietschel M, Nothen MM, Georgi A, Schumacher J, Schwarz M, Abou Jamra R, Hofels S, Propping P, Satagopan J, Detera-Wadleigh SD, Hardy J, McMahon FJ (2008) A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder. Mol Psychiatry 13(2):197–207
Beattie MS, Harrington AW, Lee R, Kim JY, Boyce SL, Longo FM, Bresnahan JC, Hempstead BL, Yoon SO (2002) ProNGF induces p75-mediated death of oligodendrocytes following spinal cord injury. Neuron 36(3):375–386
Bohm C, Seibel NM, Henkel B, Steiner H, Haass C, Hampe W (2006) SorLA signaling by regulated intramembrane proteolysis. J Biol Chem 281(21):14547–14553
Bonifacino JS, Rojas R (2006) Retrograde transport from endosomes to the trans-Golgi network. Nat Rev Mol Cell Biol 7(8):568–579
Botta R, Lisi S, Pinchera A, Giorgi F, Marcocci C, Taddei AR, Fausto AM, Bernardini N, Ippolito C, Mattii L, Persani L, de Filippis T, Calebiro D, Madsen P, Petersen CM, Marino M (2009) Sortilin is a putative postendocytic receptor of thyroglobulin. Endocrinology 150(1):509–518
Bronfman FC (2007) Metalloproteases and gamma-secretase: new membrane partners regulating p75 neurotrophin receptor signaling? J Neurochem 103(Suppl 1):91–100
Bronfman FC, Tcherpakov M, Jovin TM, Fainzilber M (2003) Ligand-induced internalization of the p75 neurotrophin receptor: a slow route to the signaling endosome. J Neurosci 23(8):3209–3220
Bruno MA, Cuello AC (2006) Activity-dependent release of precursor nerve growth factor, conversion to mature nerve growth factor, and its degradation by a protease cascade. Proc Natl Acad Sci U S A 103(17):6735–6740
Capsoni S, Tiveron C, Vignone D, Amato G, Cattaneo A (2010) Dissecting the involvement of tropomyosin-related kinase A and p75 neurotrophin receptor signaling in NGF deficit-induced neurodegeneration. Proc Natl Acad Sci U S A 107(27):12299–12304
Casaccia-Bonnefil P, Carter BD, Dobrowsky RT, Chao MV (1996) Death of oligodendrocytes mediated by the interaction of nerve growth factor with its receptor p75. Nature 383(6602):716–719
Chen ZY, Patel PD, Sant G, Meng CX, Teng KK, Hempstead BL, Lee FS (2004) Variant brain-derived neurotrophic factor (BDNF) (Met66) alters the intracellular trafficking and activity-dependent secretion of wild-type BDNF in neurosecretory cells and cortical neurons. J Neurosci 24(18):4401–4411
Chen ZY, Ieraci A, Teng H, Dall H, Meng CX, Herrera DG, Nykjaer A, Hempstead BL, Lee FS (2005) Sortilin controls intracellular sorting of brain-derived neurotrophic factor to the regulated secretory pathway. J Neurosci 25(26):6156–6166
Christoforou A, McGhee KA, Morris SW, Thomson PA, Anderson S, McLean A, Torrance HS, Le Hellard S, Pickard BS, StClair D, Muir WJ, Blackwood DH, Porteous DJ, Evans KL (2011) Convergence of linkage, association and GWAS findings for a candidate region for bipolar disorder and schizophrenia on chromosome 4p. Mol Psychiatry 16(3):240–242
Clee SM, Yandell BS, Schueler KM, Rabaglia ME, Richards OC, Raines SM, Kabara EA, Klass DM, Mui ET, Stapleton DS, Gray-Keller MP, Young MB, Stoehr JP, Lan H, Boronenkov I, Raess PW, Flowers MT, Attie AD (2006) Positional cloning of Sorcs1, a type 2 diabetes quantitative trait locus. Nat Genet 38(6):688–693
Counts SE, Nadeem M, Wuu J, Ginsberg SD, Saragovi HU, Mufson EJ (2004) Reduction of cortical TrkA but not p75(NTR) protein in early-stage Alzheimer’s disease. Ann Neurol 56(4):520–531
Davis S, Aldrich TH, Stahl N, Pan L, Taga T, Kishimoto T, Ip NY, Yancopoulos GD (1993) LIFR beta and gp130 as heterodimerizing signal transducers of the tripartite CNTF receptor. Science 260(5115):1805–1808
Domeniconi M, Hempstead BL, Chao MV (2007) Pro-NGF secreted by astrocytes promotes motor neuron cell death. Mol Cell Neurosci 34(2):271–279
Dube JB, Johansen CT, Hegele RA (2011) Sortilin: an unusual suspect in cholesterol metabolism: from GWAS identification to in vivo biochemical analyses, sortilin has been identified as a novel mediator of human lipoprotein metabolism. Bioessays 33(6):430–437
Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, Zaitsev E, Gold B, Goldman D, Dean M, Lu B, Weinberger DR (2003) The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 112(2):257–269
Ernfors P, Lee KF, Kucera J, Jaenisch R (1994) Lack of neurotrophin-3 leads to deficiencies in the peripheral nervous system and loss of limb proprioceptive afferents. Cell 77(4):503–512
Fahnestock M, Michalski B, Xu B, Coughlin MD (2001) The precursor pro-nerve growth factor is the predominant form of nerve growth factor in brain and is increased in Alzheimer’s disease. Mol Cell Neurosci 18(2):210–220
Fahnestock M, Yu G, Michalski B, Mathew S, Colquhoun A, Ross GM, Coughlin MD (2004) The nerve growth factor precursor proNGF exhibits neurotrophic activity but is less active than mature nerve growth factor. J Neurochem 89(3):581–592
Fauchais AL, Lalloue F, Lise MC, Boumediene A, Preud’homme JL, Vidal E, Jauberteau MO (2008) Role of endogenous brain-derived neurotrophic factor and sortilin in B cell survival. J Immunol 181(5):3027–3038
Feng D, Kim T, Ozkan E, Light M, Torkin R, Teng KK, Hempstead BL, Garcia KC (2010) Molecular and structural insight into proNGF engagement of p75NTR and sortilin. J Mol Biol 396(4):967–984
Friedman B, Scherer SS, Rudge JS, Helgren M, Morrisey D, McClain J, Wang DY, Wiegand SJ, Furth ME, Lindsay RM et al (1992) Regulation of ciliary neurotrophic factor expression in myelin-related Schwann cells in vivo. Neuron 9(2):295–305
Gearing DP, Ziegler SF, Comeau MR, Friend D, Thoma B, Cosman D, Park L, Mosley B (1994) Proliferative responses and binding properties of hematopoietic cells transfected with low-affinity receptors for leukemia inhibitory factor, oncostatin M, and ciliary neurotrophic factor. Proc Natl Acad Sci U S A 91(3):1119–1123
Goodarzi MO, Lehman DM, Taylor KD, Guo X, Cui J, Quinones MJ, Clee SM, Yandell BS, Blangero J, Hsueh WA, Attie AD, Stern MP, Rotter JI (2007) SORCS1: a novel human type 2 diabetes susceptibility gene suggested by the mouse. Diabetes 56(7):1922–1929
Grupe A, Li Y, Rowland C, Nowotny P, Hinrichs AL, Smemo S, Kauwe JS, Maxwell TJ, Cherny S, Doil L, Tacey K, van Luchene R, Myers A, Wavrant-De Vrieze F, Kaleem M, Hollingworth P, Jehu L, Foy C, Archer N, Hamilton G, Holmans P, Morris CM, Catanese J, Sninsky J, White TJ, Powell J, Hardy J, O’Donovan M, Lovestone S, Jones L, Morris JC, Thal L, Owen M, Williams J, Goate A (2006) A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease. Am J Hum Genet 78(1):78–88
Hampe W, Riedel IB, Lintzel J, Bader CO, Franke I, Schaller HC (2000) Ectodomain shedding, translocation and synthesis of SorLA are stimulated by its ligand head activator. J Cell Sci 113(Pt 24):4475–4485
Hariri AR, Goldberg TE, Mattay VS, Kolachana BS, Callicott JH, Egan MF, Weinberger DR (2003) Brain-derived neurotrophic factor val66met polymorphism affects human memory-related hippocampal activity and predicts memory performance. J Neurosci 23(17):6690–6694
Harrington AW, Leiner B, Blechschmitt C, Arevalo JC, Lee R, Morl K, Meyer M, Hempstead BL, Yoon SO, Giehl KM (2004) Secreted proNGF is a pathophysiological death-inducing ligand after adult CNS injury. Proc Natl Acad Sci U S A 101(16):6226–6230
Hasan W, Pedchenko T, Krizsan-Agbas D, Baum L, Smith PG (2003) Sympathetic neurons synthesize and secrete pro-nerve growth factor protein. J Neurobiol 57(1):38–53
Hermans-Borgmeyer I, Hermey G, Nykjaer A, Schaller C (1999) Expression of the 100-kDa neurotensin receptor sortilin during mouse embryonal development. Brain Res Mol Brain Res 65(2):216–219
Hermey G (2009) The Vps10p-domain receptor family. Cell Mol Life Sci 66(16):2677–2689
Hermey G, Riedel IB, Rezgaoui M, Westergaard UB, Schaller C, Hermans-Borgmeyer I (2001) SorCS1, a member of the novel sorting receptor family, is localized in somata and dendrites of neurons throughout the murine brain. Neurosci Lett 313(1–2):83–87
Hermey G, Keat SJ, Madsen P, Jacobsen C, Petersen CM, Gliemann J (2003) Characterization of sorCS1, an alternatively spliced receptor with completely different cytoplasmic domains that mediate different trafficking in cells. J Biol Chem 278(9):7390–7396
Hermey G, Plath N, Hubner CA, Kuhl D, Schaller HC, Hermans-Borgmeyer I (2004) The three sorCS genes are differentially expressed and regulated by synaptic activity. J Neurochem 88(6):1470–1476
Hermey G, Sjogaard SS, Petersen CM, Nykjaer A, Gliemann J (2006) Tumour necrosis factor alpha-converting enzyme mediates ectodomain shedding of Vps10p-domain receptor family members. Biochem J 395(2):285–293
Hu F, Padukkavidana T, Vaegter CB, Brady OA, Zheng Y, Mackenzie IR, Feldman HH, Nykjaer A, Strittmatter SM (2010) Sortilin-mediated endocytosis determines levels of the frontotemporal dementia protein, progranulin. Neuron 68(4):654–667
Jacobsen L, Madsen P, Moestrup SK, Lund AH, Tommerup N, Nykjaer A, Sottrup-Jensen L, Gliemann J, Petersen CM (1996) Molecular characterization of a novel human hybrid-type receptor that binds the alpha2-macroglobulin receptor-associated protein. J Biol Chem 271(49):31379–31383
Jacobsen L, Madsen P, Jacobsen C, Nielsen MS, Gliemann J, Petersen CM (2001) Activation and functional characterization of the mosaic receptor SorLA/LR11. J Biol Chem 276(25):22788–22796
Jansen P, Giehl K, Nyengaard JR, Teng K, Lioubinski O, Sjoegaard SS, Breiderhoff T, Gotthardt M, Lin F, Eilers A, Petersen CM, Lewin GR, Hempstead BL, Willnow TE, Nykjaer A (2007) Roles for the pro-neurotrophin receptor sortilin in neuronal development, aging and brain injury. Nat Neurosci 10(11):1449–1457
Kathiresan S, Melander O, Guiducci C, Surti A, Burtt NP, Rieder MJ, Cooper GM, Roos C, Voight BF, Havulinna AS, Wahlstrand B, Hedner T, Corella D, Tai ES, Ordovas JM, Berglund G, Vartiainen E, Jousilahti P, Hedblad B, Taskinen MR, Newton-Cheh C, Salomaa V, Peltonen L, Groop L, Altshuler DM, Orho-Melander M (2008) Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans. Nat Genet 40(2):189–197
Kenchappa RS, Zampieri N, Chao MV, Barker PA, Teng HK, Hempstead BL, Carter BD (2006) Ligand-dependent cleavage of the P75 neurotrophin receptor is necessary for NRIF nuclear translocation and apoptosis in sympathetic neurons. Neuron 50(2):219–232
Kim T, Hempstead BL (2009) NRH2 is a trafficking switch to regulate sortilin localization and permit proneurotrophin-induced cell death. EMBO J 28(11):1612–1623
Kjolby M, Andersen OM, Breiderhoff T, Fjorback AW, Pedersen KM, Madsen P, Jansen P, Heeren J, Willnow TE, Nykjaer A (2010) Sort1, encoded by the cardiovascular risk locus 1p13.3, is a regulator of hepatic lipoprotein export. Cell Metab 12(3):213–223
Klein R, Smeyne RJ, Wurst W, Long LK, Auerbach BA, Joyner AL, Barbacid M (1993) Targeted disruption of the trkB neurotrophin receptor gene results in nervous system lesions and neonatal death. Cell 75(1):113–122
Kwon S, Christian JL (2011) Sortilin associates with transforming growth factor-{beta} family proteins to enhance lysosome-mediated degradation. J Biol Chem 286(24):21876–21885
Larsen JV, Hansen M, Moller B, Madsen P, Scheller J, Nielsen M, Petersen CM (2010) Sortilin facilitates signaling of ciliary neurotrophic factor and related helical type 1 cytokines targeting the gp130/leukemia inhibitory factor receptor beta heterodimer. Mol Cell Biol 30(17):4175–4187
Lee R, Kermani P, Teng KK, Hempstead BL (2001) Regulation of cell survival by secreted proneurotrophins. Science 294(5548):1945–1948
Lefrancois S, Zeng J, Hassan AJ, Canuel M, Morales CR (2003) The lysosomal trafficking of sphingolipid activator proteins (SAPs) is mediated by sortilin. EMBO J 22(24):6430–6437
Lin BZ, Pilch PF, Kandror KV (1997) Sortilin is a major protein component of Glut4-containing vesicles. J Biol Chem 272(39):24145–24147
Mackenzie IR, Rademakers R, Neumann M (2010) TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia. Lancet Neurol 9(10):995–1007
Marcusson EG, Horazdovsky BF, Cereghino JL, Gharakhanian E, Emr SD (1994) The sorting receptor for yeast vacuolar carboxypeptidase Y is encoded by the VPS10 gene. Cell 77(4):579–586
Masoudi R, Ioannou MS, Coughlin MD, Pagadala P, Neet KE, Clewes O, Allen SJ, Dawbarn D, Fahnestock M (2009) Biological activity of nerve growth factor precursor is dependent upon relative levels of its receptors. J Biol Chem 284(27):18424–18433
Mazella J, Zsurger N, Navarro V, Chabry J, Kaghad M, Caput D, Ferrara P, Vita N, Gully D, Maffrand JP, Vincent JP (1998) The 100-kDa neurotensin receptor is gp95/sortilin, a non-G-protein-coupled receptor. J Biol Chem 273(41):26273–26276
Minichiello L, Piehl F, Vazquez E, Schimmang T, Hokfelt T, Represa J, Klein R (1995) Differential effects of combined trk receptor mutations on dorsal root ganglion and inner ear sensory neurons. Development 121(12):4067–4075
Morris NJ, Ross SA, Lane WS, Moestrup SK, Petersen CM, Keller SR, Lienhard GE (1998) Sortilin is the major 110-kDa protein in GLUT4 vesicles from adipocytes. J Biol Chem 273(6):3582–3587
Mowla SJ, Pareek S, Farhadi HF, Petrecca K, Fawcett JP, Seidah NG, Morris SJ, Sossin WS, Murphy RA (1999) Differential sorting of nerve growth factor and brain-derived neurotrophic factor in hippocampal neurons. J Neurosci 19(6):2069–2080
Mufson EJ, Wuu J, Counts SE, Nykjaer A (2010) Preservation of cortical sortilin protein levels in MCI and Alzheimer’s disease. Neurosci Lett 471(3):129–133
Munck Petersen C, Nielsen MS, Jacobsen C, Tauris J, Jacobsen L, Gliemann J, Moestrup SK, Madsen P (1999) Propeptide cleavage conditions sortilin/neurotensin receptor-3 for ligand binding. EMBO J 18(3):595–604
Musunuru K, Strong A, Frank-Kamenetsky M, Lee NE, Ahfeldt T, Sachs KV, Li X, Li H, Kuperwasser N, Ruda VM, Pirruccello JP, Muchmore B, Prokunina-Olsson L, Hall JL, Schadt EE, Morales CR, Lund-Katz S, Phillips MC, Wong J, Cantley W, Racie T, Ejebe KG, Orho-Melander M, Melander O, Koteliansky V, Fitzgerald K, Krauss RM, Cowan CA, Kathiresan S, Rader DJ (2010) From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus. Nature 466(7307):714–719
Nakamura K, Namekata K, Harada C, Harada T (2007) Intracellular sortilin expression pattern regulates proNGF-induced naturally occurring cell death during development. Cell Death Differ 14(8):1552–1554
Neves-Pereira M, Mundo E, Muglia P, King N, Macciardi F, Kennedy JL (2002) The brain-derived neurotrophic factor gene confers susceptibility to bipolar disorder: evidence from a family-based association study. Am J Hum Genet 71(3):651–655
Nielsen MS, Jacobsen C, Olivecrona G, Gliemann J, Petersen CM (1999) Sortilin/neurotensin receptor-3 binds and mediates degradation of lipoprotein lipase. J Biol Chem 274(13):8832–8836
Nielsen MS, Madsen P, Christensen EI, Nykjaer A, Gliemann J, Kasper D, Pohlmann R, Petersen CM (2001) The sortilin cytoplasmic tail conveys Golgi-endosome transport and binds the VHS domain of the GGA2 sorting protein. EMBO J 20(9):2180–2190
Nielsen MS, Gustafsen C, Madsen P, Nyengaard JR, Hermey G, Bakke O, Mari M, Schu P, Pohlmann R, Dennes A, Petersen CM (2007) Sorting by the cytoplasmic domain of the amyloid precursor protein binding receptor SorLA. Mol Cell Biol 27(19):6842–6851
Nielsen MS, Keat SJ, Hamati JW, Madsen P, Gutzmann JJ, Engelsberg A, Pedersen KM, Gustafsen C, Nykjaer A, Gliemann J, Hermans-Borgmeyer I, Kuhl D, Petersen CM, Hermey G (2008) Different motifs regulate trafficking of SorCS1 isoforms. Traffic 9(6):980–994
Nykjaer A, Lee R, Teng KK, Jansen P, Madsen P, Nielsen MS, Jacobsen C, Kliemannel M, Schwarz E, Willnow TE, Hempstead BL, Petersen CM (2004) Sortilin is essential for proNGF-induced neuronal cell death. Nature 427(6977):843–848
Ollila HM, Soronen P, Silander K, Palo OM, Kieseppa T, Kaunisto MA, Lonnqvist J, Peltonen L, Partonen T, Paunio T (2009) Findings from bipolar disorder genome-wide association studies replicate in a Finnish bipolar family-cohort. Mol Psychiatry 14(4):351–353
Oppenheim RW, Prevette D, Yin QW, Collins F, MacDonald J (1991) Control of embryonic motoneuron survival in vivo by ciliary neurotrophic factor. Science 251(5001):1616–1618
Peng S, Wuu J, Mufson EJ, Fahnestock M (2004) Increased proNGF levels in subjects with mild cognitive impairment and mild Alzheimer disease. J Neuropathol Exp Neurol 63(6):641–649
Petersen CM, Nielsen MS, Nykjaer A, Jacobsen L, Tommerup N, Rasmussen HH, Roigaard H, Gliemann J, Madsen P, Moestrup SK (1997) Molecular identification of a novel candidate sorting receptor purified from human brain by receptor-associated protein affinity chromatography. J Biol Chem 272(6):3599–3605
Podlesniy P, Kichev A, Pedraza C, Saurat J, Encinas M, Perez B, Ferrer I, Espinet C (2006) Pro-NGF from Alzheimer’s disease and normal human brain displays distinctive abilities to induce processing and nuclear translocation of intracellular domain of p75NTR and apoptosis. Am J Pathol 169(1):119–131
Provenzano MJ, Xu N, Ver Meer MR, Clark JJ, Hansen MR (2008) p75NTR and sortilin increase after facial nerve injury. Laryngoscope 118(1):87–93
Quistgaard EM, Madsen P, Groftehauge MK, Nissen P, Petersen CM, Thirup SS (2009) Ligands bind to Sortilin in the tunnel of a ten-bladed beta-propeller domain. Nat Struct Mol Biol 16(1):96–98
Reichardt LF (2006) Neurotrophin-regulated signalling pathways. Philos Trans R Soc Lond B Biol Sci 361(1473):1545–1564
Reiche J, Theilig F, Rafiqi FH, Carlo AS, Militz D, Mutig K, Todiras M, Christensen EI, Ellison DH, Bader M, Nykjaer A, Bachmann S, Alessi D, Willnow TE (2010) SORLA/SORL1 functionally interacts with SPAK to control renal activation of Na(+)-K(+)-Cl(−) cotransporter 2. Mol Cell Biol 30(12):3027–3037
Reitz C, Cheng R, Rogaeva E, Lee JH, Tokuhiro S, Zou F, Bettens K, Sleegers K, Tan EK, Kimura R, Shibata N, Arai H, Kamboh MI, Prince JA, Maier W, Riemenschneider M, Owen M, Harold D, Hollingworth P, Cellini E, Sorbi S, Nacmias B, Takeda M, Pericak-Vance MA, Haines JL, Younkin S, Williams J, van Broeckhoven C, Farrer LA, St George-Hyslop PH, Mayeux R (2011a) Meta-analysis of the association between variants in SORL1 and Alzheimer disease. Arch Neurol 68(1):99–106
Reitz C, Tokuhiro S, Clark LN, Conrad C, Vonsattel JP, Hazrati LN, Palotas A, Lantigua R, Medrano M, Z Jiménez-Velázquez I, Vardarajan B, Simkin I, Haines JL, Pericak-Vance MA, Farrer LA, Lee JH, Rogaeva E, George-Hyslop PS, Mayeux R (2011b) SORCS1 alters amyloid precursor protein processing and variants may increase Alzheimer’s disease risk. Ann Neurol 69(1):47–64
Rezgaoui M, Hermey G, Riedel IB, Hampe W, Schaller HC, Hermans-Borgmeyer I (2001) Identification of SorCS2, a novel member of the VPS10 domain containing receptor family, prominently expressed in the developing mouse brain. Mech Dev 100(2):335–338
Rogaeva E, Meng Y, Lee JH, Gu Y, Kawarai T, Zou F, Katayama T, Baldwin CT, Cheng R, Hasegawa H, Chen F, Shibata N, Lunetta KL, Pardossi-Piquard R, Bohm C, Wakutani Y, Cupples LA, Cuenco KT, Green RC, Pinessi L, Rainero I, Sorbi S, Bruni A, Duara R, Friedland RP, Inzelberg R, Hampe W, Bujo H, Song YQ, Andersen OM, Willnow TE, Graff-Radford N, Petersen RC, Dickson D, Der SD, Fraser PE, Schmitt-Ulms G, Younkin S, Mayeux R, Farrer LA, St George-Hyslop P (2007) The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease. Nat Genet 39(2):168–177
Rudge JS, Pasnikowski EM, Holst P, Lindsay RM (1995) Changes in neurotrophic factor expression and receptor activation following exposure of hippocampal neuron/astrocyte cocultures to kainic acid. J Neurosci 15(10):6856–6867
Rybakowski JK, Borkowska A, Czerski PM, Skibinska M, Hauser J (2003) Polymorphism of the brain-derived neurotrophic factor gene and performance on a cognitive prefrontal test in bipolar patients. Bipolar Disord 5(6):468–472
Sandhu MS, Waterworth DM, Debenham SL, Wheeler E, Papadakis K, Zhao JH, Song K, Yuan X, Johnson T, Ashford S, Inouye M, Luben R, Sims M, Hadley D, McArdle W, Barter P, Kesaniemi YA, Mahley RW, McPherson R, Grundy SM, Bingham SA, Khaw KT, Loos RJ, Waeber G, Barroso I, Strachan DP, Deloukas P, Vollenweider P, Wareham NJ, Mooser V (2008) LDL-cholesterol concentrations: a genome-wide association study. Lancet 371(9611):483–491
Sarret P, Krzywkowski P, Segal L, Nielsen MS, Petersen CM, Mazella J, Stroh T, Beaudet A (2003) Distribution of NTS3 receptor/sortilin mRNA and protein in the rat central nervous system. J Comp Neurol 461(4):483–505
Scherzer CR, Offe K, Gearing M, Rees HD, Fang G, Heilman CJ, Schaller C, Bujo H, Levey AI, Lah JJ (2004) Loss of apolipoprotein E receptor LR11 in Alzheimer disease. Arch Neurol 61(8):1200–1205
Schmidt V, Sporbert A, Rohe M, Reimer T, Rehm A, Andersen OM, Willnow TE (2007) SorLA/LR11 regulates processing of amyloid precursor protein via interaction with adaptors GGA and PACS-1. J Biol Chem 282(45):32956–32964
Sen S, Nesse RM, Stoltenberg SF, Li S, Gleiberman L, Chakravarti A, Weder AB, Burmeister M (2003) A BDNF coding variant is associated with the NEO personality inventory domain neuroticism, a risk factor for depression. Neuropsychopharmacology 28(2):397–401
Sendtner M, Stockli KA, Thoenen H (1992) Synthesis and localization of ciliary neurotrophic factor in the sciatic nerve of the adult rat after lesion and during regeneration. J Cell Biol 118(1):139–148
Shi J, Kandror KV (2005) Sortilin is essential and sufficient for the formation of Glut4 storage vesicles in 3T3-L1 adipocytes. Dev Cell 9(1):99–108
Simon R, Thier M, Kruttgen A, Rose-John S, Weiergraber O, Heinrich PC, Schroder JM, Weis J (1995) Human CNTF and related cytokines: effects on DRG neurone survival. Neuroreport 7(1):153–157
Sklar P, Gabriel SB, McInnis MG, Bennett P, Lim YM, Tsan G, Schaffner S, Kirov G, Jones I, Owen M, Craddock N, DePaulo JR, Lander ES (2002) Family-based association study of 76 candidate genes in bipolar disorder: BDNF is a potential risk locus. Brain-derived neutrophic factor. Mol Psychiatry 7(6):579–593
Srinivasan B, Roque CH, Hempstead BL, Al-Ubaidi MR, Roque RS (2004) Microglia-derived pronerve growth factor promotes photoreceptor cell death via p75 neurotrophin receptor. J Biol Chem 279(40):41839–41845
Srinivasan B, Wang Z, Brun-Zinkernagel AM, Collier RJ, Black RA, Frank SJ, Barker PA, Roque RS (2007) Photic injury promotes cleavage of p75NTR by TACE and nuclear trafficking of the p75 intracellular domain. Mol Cell Neurosci 36(4):449–461
Stoehr JP, Nadler ST, Schueler KL, Rabaglia ME, Yandell BS, Metz SA, Attie AD (2000) Genetic obesity unmasks nonlinear interactions between murine type 2 diabetes susceptibility loci. Diabetes 49(11):1946–1954
Stoica G, Lungu G, Kim HT, Wong PK (2008) Up-regulation of pro-nerve growth factor, neurotrophin receptor p75, and sortilin is associated with retrovirus-induced spongiform encephalomyelopathy. Brain Res 1208:204–216
Tauris J, Gustafsen C, Christensen EI, Jansen P, Nykjaer A, Nyengaard JR, Teng KK, Schwarz E, Ovesen T, Madsen P, Petersen CM (2011) Proneurotrophin-3 may induce Sortilin-dependent death in inner ear neurons. Eur J Neurosci 33(4):622–631
Teng HK, Teng KK, Lee R, Wright S, Tevar S, Almeida RD, Kermani P, Torkin R, Chen ZY, Lee FS, Kraemer RT, Nykjaer A, Hempstead BL (2005) ProBDNF induces neuronal apoptosis via activation of a receptor complex of p75NTR and sortilin. J Neurosci 25(22):5455–5463
Tollervey JR, Curk T, Rogelj B, Briese M, Cereda M, Kayikci M, Konig J, Hortobagyi T, Nishimura AL, Zupunski V, Patani R, Chandran S, Rot G, Zupan B, Shaw CE, Ule J (2011) Characterizing the RNA targets and position-dependent splicing regulation by TDP-43. Nat Neurosci 14(4):452–458
Vaegter CB, Jansen P, Fjorback AW, Glerup S, Skeldal S, Kjolby M, Richner M, Erdmann B, Nyengaard JR, Tessarollo L, Lewin GR, Willnow TE, Chao MV, Nykjaer A (2011) Sortilin associates with Trk receptors to enhance anterograde transport and neurotrophin signaling. Nat Neurosci 14(1):54–61
Volosin M, Song W, Almeida RD, Kaplan DR, Hempstead BL, Friedman WJ (2006) Interaction of survival and death signaling in basal forebrain neurons: roles of neurotrophins and proneurotrophins. J Neurosci 26(29):7756–7766
Volosin M, Trotter C, Cragnolini A, Kenchappa RS, Light M, Hempstead BL, Carter BD, Friedman WJ (2008) Induction of proneurotrophins and activation of p75NTR-mediated apoptosis via neurotrophin receptor-interacting factor in hippocampal neurons after seizures. J Neurosci 28(39):9870–9879
Wahe A, Kasmapour B, Schmaderer C, Liebl D, Sandhoff K, Nykjaer A, Griffiths G, Gutierrez MG (2010) Golgi-to-phagosome transport of acid sphingomyelinase and prosaposin is mediated by sortilin. J Cell Sci 123(Pt 14):2502–2511
Wei Y, Wang N, Lu Q, Zhang N, Zheng D, Li J (2007) Enhanced protein expressions of sortilin and p75NTR in retina of rat following elevated intraocular pressure-induced retinal ischemia. Neurosci Lett 429(2–3):169–174
Westergaard UB, Kirkegaard K, Sorensen ES, Jacobsen C, Nielsen MS, Petersen CM, Madsen P (2005) SorCS3 does not require propeptide cleavage to bind nerve growth factor. FEBS Lett 579(5):1172–1176
Willer CJ, Sanna S, Jackson AU, Scuteri A, Bonnycastle LL, Clarke R, Heath SC, Timpson NJ, Najjar SS, Stringham HM, Strait J, Duren WL, Maschio A, Busonero F, Mulas A, Albai G, Swift AJ, Morken MA, Narisu N, Bennett D, Parish S, Shen H, Galan P, Meneton P, Hercberg S, Zelenika D, Chen WM, Li Y, Scott LJ, Scheet PA, Sundvall J, Watanabe RM, Nagaraja R, Ebrahim S, Lawlor DA, Ben-Shlomo Y, Davey-Smith G, Shuldiner AR, Collins R, Bergman RN, Uda M, Tuomilehto J, Cao A, Collins FS, Lakatta E, Lathrop GM, Boehnke M, Schlessinger D, Mohlke KL, Abecasis GR (2008) Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet 40(2):161–169
Willnow TE, Petersen CM, Nykjaer A (2008) VPS10P-domain receptors – regulators of neuronal viability and function. Nat Rev Neurosci 9(12):899–909
Willnow TE, Kjolby M, Nykjaer A (2011) Sortilins: new players in lipoprotein metabolism. Curr Opin Lipidol 22(2):79–85
Yamashita T, Fujitani M, Hata K, Mimura F, Yamagishi S (2005) Diverse functions of the p75 neurotrophin receptor. Anat Sci Int 80(1):37–41
Yang J, Siao CJ, Nagappan G, Marinic T, Jing D, McGrath K, Chen ZY, Mark W, Tessarollo L, Lee FS, Lu B, Hempstead BL (2009) Neuronal release of proBDNF. Nat Neurosci 12(2):113–115
Yang M, Lim Y, Li X, Zhong JH, Zhou XF (2011) Precursor of brain-derived neurotrophic factor (proBDNF) forms a complex with Huntingtin associated protein-1 (HAP1) and sortilin that modulates proBDNF trafficking, degradation and processing. J Biol Chem 286(18):16272–16284
Yano H, Torkin R, Martin LA, Chao MV, Teng KK (2009) Proneurotrophin-3 is a neuronal apoptotic ligand: evidence for retrograde-directed cell killing. J Neurosci 29(47):14790–14802
Yoon SO, Casaccia-Bonnefil P, Carter B, Chao MV (1998) Competitive signaling between TrkA and p75 nerve growth factor receptors determines cell survival. J Neurosci 18(9):3273–3281
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer-Verlag Berlin Heidelberg 2014
About this chapter
Cite this chapter
Glerup, S., Nykjaer, A., Vaegter, C.B. (2014). Sortilins in Neurotrophic Factor Signaling. In: Lewin, G., Carter, B. (eds) Neurotrophic Factors. Handbook of Experimental Pharmacology, vol 220. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-45106-5_7
Download citation
DOI: https://doi.org/10.1007/978-3-642-45106-5_7
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-45105-8
Online ISBN: 978-3-642-45106-5
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)