Psychiatric Implication of Synaptic Adhesion Molecules and Scaffold Proteins

시냅스 접착 단백질과 구조 단백질의 정신과적 의의

  • Oh, Daeyoung (National Creative Research Initiative Center for Synaptogenesis and Department of Biological Sciences, Korea Advanced Institute of Science and Technology(KAIST))
  • 오대영 (한국과학기술원 생명과학과 시냅스생성 창의연구단, 분자신경생물학교실)
  • Received : 2010.07.09
  • Accepted : 2010.08.01
  • Published : 2010.08.31

Abstract

Synaptic adhesion molecules mediate synapse formation, maturation and maintenance. These proteins are localized at synaptic sites in neuronal axons and dendrites. These proteins function as a bridge of synaptic cleft via interaction with another synaptic adhesion molecules in the opposite side. They can interact with scaffold proteins via intracellular domain and recruit many synaptic proteins, signaling proteins and synaptic vesicles. Scaffold proteins function as a platform in dendritic spines or axonal terminals. Recently, many genetic studies have revealed that synaptic adhesion molecules and scaffold proteins are important in neurodevelopmental disorders, psychotic disorders, mood disorders and anxiety disorders. In this review, fundamental mechanisms of synapse formation and maturation related with synaptic adhesion molecules and scaffold proteins are introduced and their psychiatric implications addressed.

Keywords

References

  1. Dalva MB, McClelland AC, Kayser MS. Cell adhesion molecules: signalling functions at the synapse. Nat Rev Neurosci 2007;8:206-220.
  2. Kim S, Burette A, Chung HS, Kwon SK, Woo J, Lee HW, et al. NGL family PSD-95-interacting adhesion molecules regulate excitatory synapse formation. Nat Neurosci 2006;9:1294-1301. https://doi.org/10.1038/nn1763
  3. Kim E, Sheng M. The postsynaptic density. Curr Biol 2009;19:R723-R724. https://doi.org/10.1016/j.cub.2009.07.047
  4. Brose N, O'Connor V, Skehel P. Synaptopathy: dysfunction of synaptic function? Biochem Soc Trans 2010; 38:443-444. https://doi.org/10.1042/BST0380443
  5. Betancur C, Sakurai T, Buxbaum JD. The emerging role of synaptic cell-adhesion pathways in the pathogenesis of autism spectrum disorders. Trends Neurosci 2009; 32:402-412. https://doi.org/10.1016/j.tins.2009.04.003
  6. Durand CM, Betancur C, Boeckers TM, Bockmann J, Chaste P, Fauchereau F, et al. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat Genet 2007;39:25-27. https://doi.org/10.1038/ng1933
  7. McAllister AK. Dynamic aspects of CNS synapse formation. Annu Rev Neurosci 2007;30:425-450. https://doi.org/10.1146/annurev.neuro.29.051605.112830
  8. Waites CL, Craig AM, Garner CC. Mechanisms of vertebrate synaptogenesis. Annu Rev Neurosci 2005;28:251-274. https://doi.org/10.1146/annurev.neuro.27.070203.144336
  9. Li Z, Sheng M. Some assembly required: the development of neuronal synapses. Nat Rev Mol Cell Biol 2003; 4:833-841. https://doi.org/10.1038/nrm1242
  10. Valtschanoff JG, Weinberg RJ. Laminar organization of the NMDA receptor complex within the postsynaptic density. J Neurosci 2001;21:1211-1217.
  11. Petersen JD, Chen X, Vinade L, Dosemeci A, Lisman JE, Reese TS. Distribution of postsynaptic density(PSD)- 95 and Ca2+/calmodulin-dependent protein kinase II at the PSD. J Neurosci 2003;23:11270-11278.
  12. Brose N. Synaptogenic proteins and synaptic organizers: "many hands make light work". Neuron 2009;61:650-652. https://doi.org/10.1016/j.neuron.2009.02.014
  13. Aoto J, Chen L. Bidirectional ephrin/Eph signaling in synaptic functions. Brain Res 2007;1184:72-80. https://doi.org/10.1016/j.brainres.2006.11.033
  14. Craig AM, Kang Y. Neurexin-neuroligin signaling in synapse development. Curr Opin Neurobiol 2007;17:43-52. https://doi.org/10.1016/j.conb.2007.01.011
  15. Gerrow K, El-Husseini A. Cell adhesion molecules at the synapse. Front Biosci 2006;11:2400-2419. https://doi.org/10.2741/1978
  16. Tai CY, Kim SA, Schuman EM. Cadherins and synaptic plasticity. Curr Opin Cell Biol 2008;20:567-575. https://doi.org/10.1016/j.ceb.2008.06.003
  17. Yamagata M, Sanes JR, Weiner JA. Synaptic adhesion molecules. Curr Opin Cell Biol 2003;15:621-632. https://doi.org/10.1016/S0955-0674(03)00107-8
  18. Ullrich B, Ushkaryov YA, Sudhof TC. Cartography of neurexins: more than 1000 isoforms generated by alternative splicing and expressed in distinct subsets of neurons. Neuron 1995;14:497-507. https://doi.org/10.1016/0896-6273(95)90306-2
  19. Ushkaryov YA, Sudhof TC. Neurexin III alpha: extensive alternative splicing generates membrane-bound and soluble forms. Proc Natl Acad Sci U S A 1993;90:6410-6414. https://doi.org/10.1073/pnas.90.14.6410
  20. Friedman HV, Bresler T, Garner CC, Ziv NE. Assembly of new individual excitatory synapses: time course and temporal order of synaptic molecule recruitment. Neuron 2000;27:57-69. https://doi.org/10.1016/S0896-6273(00)00009-X
  21. Gerrow K, Romorini S, Nabi SM, Colicos MA, Sala C, El-Husseini A. A preformed complex of postsynaptic proteins is involved in excitatory synapse development. Neuron 2006;49:547-562. https://doi.org/10.1016/j.neuron.2006.01.015
  22. Hata Y, Butz S, Sudhof TC. CASK: a novel dlg/PSD95 homolog with an N-terminal calmodulin-dependent protein kinase domain identified by interaction with neurexins. J Neurosci 1996;16:2488-2494.
  23. Biederer T, Sudhof TC. Mints as adaptors. Direct binding to neurexins and recruitment of munc18. J Biol Chem 2000;275:39803-39806. https://doi.org/10.1074/jbc.C000656200
  24. Graf ER, Zhang X, Jin SX, Linhoff MW, Craig AM. Neurexins induce differentiation of GABA and glutamate postsynaptic specializations via neuroligins. Cell 2004; 119:1013-1026. https://doi.org/10.1016/j.cell.2004.11.035
  25. Scheiffele P, Fan J, Choih J, Fetter R, Serafini T. Neuroligin expressed in nonneuronal cells triggers presynaptic development in contacting axons. Cell 2000;101:657-669. https://doi.org/10.1016/S0092-8674(00)80877-6
  26. Nam CI, Chen L. Postsynaptic assembly induced by neu-rexin-neuroligin interaction and neurotransmitter. Proc Natl Acad Sci U S A 2005;102:6137-6142. https://doi.org/10.1073/pnas.0502038102
  27. Feng J, Schroer R, Yan J, Song W, Yang C, Bockholt A, et al. High frequency of neurexin 1beta signal peptide structural variants in patients with autism. Neurosci Lett 2006;409:10-13. https://doi.org/10.1016/j.neulet.2006.08.017
  28. Kim HG, Kishikawa S, Higgins AW, Seong IS, Donovan DJ, Shen Y, et al. Disruption of neurexin 1 associated with autism spectrum disorder. Am J Hum Genet 2008; 82:199-207. https://doi.org/10.1016/j.ajhg.2007.09.011
  29. Marshall CR, Noor A, Vincent JB, Lionel AC, Feuk L, Skaug J, et al. Structural variation of chromosomes in autism spectrum disorder. Am J Hum Genet 2008;82: 477-488. https://doi.org/10.1016/j.ajhg.2007.12.009
  30. Yan J, Noltner K, Feng J, Li W, Schroer R, Skinner C, et al. Neurexin 1alpha structural variants associated with autism. Neurosci Lett 2008;438:368-370. https://doi.org/10.1016/j.neulet.2008.04.074
  31. Jamain S, Quach H, Betancur C, Ra°stam M, Colineaux C, Gillberg IC, et al. Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat Genet 2003;34:27-29. https://doi.org/10.1038/ng1136
  32. Laumonnier F, Bonnet-Brilhault F, Gomot M, Blanc R, David A, Moizard MP, et al. X-linked mental retardation and autism are associated with a mutation in the NLGN4 gene, a member of the neuroligin family. Am J Hum Genet 2004;74:552-557. https://doi.org/10.1086/382137
  33. Macarov M, Zeigler M, Newman JP, Strich D, Sury V, Tennenbaum A, et al. Deletions of VCX-A and NLGN4: a variable phenotype including normal intellect. J Intellect Disabil Res 2007;51:329-333. https://doi.org/10.1111/j.1365-2788.2006.00880.x
  34. Lawson-Yuen A, Saldivar JS, Sommer S, Picker J. Familial deletion within NLGN4 associated with autism and Tourette syndrome. Eur J Hum Genet 2008;16:614-618. https://doi.org/10.1038/sj.ejhg.5202006
  35. Kirov G, Gumus D, Chen W, Norton N, Georgieva L, Sari M, et al. Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia. Hum Mol Genet 2008;17:458-465.
  36. Tabuchi K, Blundell J, Etherton MR, Hammer RE, Liu X, Powell CM, et al. A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice. Science 2007;318:71-76. https://doi.org/10.1126/science.1146221
  37. Sudhof TC. Neuroligins and neurexins link synaptic function to cognitive disease. Nature 2008;455:903-911. https://doi.org/10.1038/nature07456
  38. Woo J, Kwon SK, Kim E. The NGL family of leucinerich repeat-containing synaptic adhesion molecules. Mol Cell Neurosci 2009;42:1-10. https://doi.org/10.1016/j.mcn.2009.05.008
  39. Lin JC, Ho WH, Gurney A, Rosenthal A. The netrin- G1 ligand NGL-1 promotes the outgrowth of thalamocortical axons. Nat Neurosci 2003;6:1270-1276. https://doi.org/10.1038/nn1148
  40. Nakashiba T, Nishimura S, Ikeda T, Itohara S. Complementary expression and neurite outgrowth activity of netrin-G subfamily members. Mech Dev 2002;111:47-60. https://doi.org/10.1016/S0925-4773(01)00600-1
  41. Woo J, Kwon SK, Choi S, Kim S, Lee JR, Dunah AW, et al. Trans-synaptic adhesion between NGL-3 and LAR regulates the formation of excitatory synapses. Nat Neurosci 2009;12:428-437. https://doi.org/10.1038/nn.2279
  42. Kwon SK, Woo J, Kim SY, Kim H, Kim E. Trans-synaptic Adhesions between Netrin-G Ligand-3(NGL-3) and Receptor Tyrosine Phosphatases LAR, Protein-tyrosine Phosphatase delta(PTP delta), and PTP sigma via Specific Domains Regulate Excitatory Synapse Formation. J Biol Chem 2010;285:13966-13978. https://doi.org/10.1074/jbc.M109.061127
  43. Stryker E, Johnson KG. LAR, liprin alpha and the regulation of active zone morphogenesis. J Cell Sci 2007; 120:3723-3728. https://doi.org/10.1242/jcs.03491
  44. Dunah AW, Hueske E, Wyszynski M, Hoogenraad CC, Jaworski J, Pak DT, et al. LAR receptor protein tyrosine phosphatases in the development and maintenance of excitatory synapses. Nat Neurosci 2005;8:458-467.
  45. Ko J, Na M, Kim S, Lee JR, Kim E. Interaction of the ERC family of RIM-binding proteins with the liprinalpha family of multidomain proteins. J Biol Chem 2003; 278:42377-42385. https://doi.org/10.1074/jbc.M307561200
  46. Ohtsuka T, Takao-Rikitsu E, Inoue E, Inoue M, Takeuchi M, Matsubara K, et al. Cast: a novel protein of the cytomatrix at the active zone of synapses that forms a ternary complex with RIM1 and munc13-1. J Cell Biol 2002;158:577-590. https://doi.org/10.1083/jcb.200202083
  47. Aoki-Suzuki M, Yamada K, Meerabux J, Iwayama- Shigeno Y, Ohba H, Iwamoto K, et al. A family-based association study and gene expression analyses of netrin- G1 and -G2 genes in schizophrenia. Biol Psychiatry 2005; 57:382-393. https://doi.org/10.1016/j.biopsych.2004.11.022
  48. Ohtsuki T, Horiuchi Y, Koga M, Ishiguro H, Inada T, Iwata N, et al. Association of polymorphisms in the haplotype block spanning the alternatively spliced exons of the NTNG1 gene at 1p13.3 with schizophrenia in Japanese populations. Neurosci Lett 2008;435:194-197. https://doi.org/10.1016/j.neulet.2008.02.053
  49. Eastwood SL, Harrison PJ. Decreased mRNA expression of netrin-G1 and netrin-G2 in the temporal lobe in schizophrenia and bipolar disorder. Neuropsychopharmacology 2008;33:933-945. https://doi.org/10.1038/sj.npp.1301457
  50. Chahrour M, Zoghbi HY. The story of Rett syndrome: from clinic to neurobiology. Neuron 2007;56:422-437. https://doi.org/10.1016/j.neuron.2007.10.001
  51. Borg I, Freude K, Kubart S, Hoffmann K, Menzel C, Laccone F, et al. Disruption of Netrin G1 by a balanced chromosome translocation in a girl with Rett syndrome. Eur J Hum Genet 2005;13:921-927. https://doi.org/10.1038/sj.ejhg.5201429
  52. Archer HL, Evans JC, Millar DS, Thompson PW, Kerr AM, Leonard H, et al. NTNG1 mutations are a rare cause of Rett syndrome. Am J Med Genet A 2006;140: 691-694.
  53. Holme RH, Kiernan BW, Brown SD, Steel KP. Elongation of hair cell stereocilia is defective in the mouse mutant whirler. J Comp Neurol 2002;450:94-102. https://doi.org/10.1002/cne.10301
  54. Delprat B, Michel V, Goodyear R, Yamasaki Y, Michalski N, El-Amraoui A, et al. Myosin XVa and whirlin, two deafness gene products required for hair bundle growth, are located at the stereocilia tips and interact directly. Hum Mol Genet 2005;14:401-410. https://doi.org/10.1093/hmg/ddi036
  55. Wu M, Huang C, Gan K, Huang H, Chen Q, Ouyang J, et al. LRRC4, a putative tumor suppressor gene, requires a functional leucine-rich repeat cassette domain to inhibit proliferation of glioma cells in vitro by modulating the extracellular signal-regulated kinase/protein kinase B/nuclear factor-kappaB pathway. Mol Biol Cell 2006;17:3534-3542. https://doi.org/10.1091/mbc.E05-11-1082
  56. Arikkath J, Reichardt LF. Cadherins and catenins at synapses: roles in synaptogenesis and synaptic plasticity. Trends Neurosci 2008;31:487-494. https://doi.org/10.1016/j.tins.2008.07.001
  57. Benson DL, Tanaka H. N-cadherin redistribution during synaptogenesis in hippocampal neurons. J Neurosci 1998; 18:6892-6904.
  58. Weiner JA, Wang X, Tapia JC, Sanes JR. Gamma protocadherins are required for synaptic development in the spinal cord. Proc Natl Acad Sci U S A 2005;102:8-14. https://doi.org/10.1073/pnas.0407931101
  59. Wang K, Zhang H, Ma D, Bucan M, Glessner JT, Abrahams BS, et al. Common genetic variants on 5p14.1 associate with autism spectrum disorders. Nature 2009; 459:528-533. https://doi.org/10.1038/nature07999
  60. Meyer G, Varoqueaux F, Neeb A, Oschlies M, Brose N. The complexity of PDZ domain-mediated interactions at glutamatergic synapses: a case study on neuroligin. Neuropharmacology 2004;47:724-733. https://doi.org/10.1016/j.neuropharm.2004.06.023
  61. Sheng M, Hoogenraad CC. The postsynaptic architecture of excitatory synapses: a more quantitative view. Annu Rev Biochem 2007;76:823-847. https://doi.org/10.1146/annurev.biochem.76.060805.160029
  62. Boeckers TM. The postsynaptic density. Cell Tissue Res 2006;326:409-422. https://doi.org/10.1007/s00441-006-0274-5
  63. Roussignol G, Ango F, Romorini S, Tu JC, Sala C, Worley PF, et al. Shank expression is sufficient to induce functional dendritic spine synapses in aspiny neurons. J Neurosci 2005;25:3560-3570. https://doi.org/10.1523/JNEUROSCI.4354-04.2005
  64. Cusmano-Ozog K, Manning MA, Hoyme HE. 22q13.3 deletion syndrome: a recognizable malformation syndrome associated with marked speech and language delay. Am J Med Genet C Semin Med Genet 2007;145C:393-398. https://doi.org/10.1002/ajmg.c.30155
  65. Wilson HL, Wong AC, Shaw SR, Tse WY, Stapleton GA, Phelan MC, et al. Molecular characterisation of the 22q13 deletion syndrome supports the role of haploinsufficiency of SHANK3/PROSAP2 in the major neurological symptoms. J Med Genet 2003;40:575-584. https://doi.org/10.1136/jmg.40.8.575
  66. Bonaglia MC, Giorda R, Borgatti R, Felisari G, Gagliardi C, Selicorni A, et al. Disruption of the ProSAP2 gene in a t(12;22)(q24.1;q13.3) is associated with the 22q13.3 deletion syndrome. Am J Hum Genet 2001;69:261-268. https://doi.org/10.1086/321293
  67. Kim E, Naisbitt S, Hsueh YP, Rao A, Rothschild A, Craig AM, et al. GKAP, a novel synaptic protein that interacts with the guanylate kinase-like domain of the PSD-95/SAP90 family of channel clustering molecules. J Cell Biol 1997;136:669-678. https://doi.org/10.1083/jcb.136.3.669
  68. Funke L, Dakoji S, Bredt DS. Membrane-associated guanylate kinases regulate adhesion and plasticity at cell junctions. Annu Rev Biochem 2005;74:219-245. https://doi.org/10.1146/annurev.biochem.74.082803.133339
  69. Welch JM, Lu J, Rodriguiz RM, Trotta NC, Peca J, Ding JD, et al. Cortico-striatal synaptic defects and OCD-like behaviours in Sapap3-mutant mice. Nature 2007;448:894-900. https://doi.org/10.1038/nature06104
  70. Bienvenu OJ, Wang Y, Shugart YY, Welch JM, Grados MA, Fyer AJ, et al. Sapap3 and pathological grooming in humans: Results from the OCD collaborative genetics study. Am J Med Genet B Neuropsychiatr Genet 2009; 150B:710-720. https://doi.org/10.1002/ajmg.b.30897