Abstract
Synaptic cell adhesion molecules (SCAMs) are mostly membrane-anchored molecules with extracellular domains that extend into the synaptic cleft. Prototypical SCAMs interact with homologous or heterologous molecules on the surface of adjacent cells, ensuring the precise apposition of pre- and postsynaptic elements. More recent definitions of SCAMs often include molecules involved in axon pathfinding, cell recognition and synaptic differentiation events, making SCAMs functionally and molecularly a highly diverse group. In this review, we summarize the proposed in vivo functions of a large variety of SCAMs. We mainly focus on results obtained from analyses of genetic model organisms, mostly mouse knockout mutants, lacking expression of the respective candidate genes. In contrast to the substantial effect yielded by some knockouts of molecules involved in synaptic vesicle release, no SCAM mutant has been reported thus far that shows a prominently altered structure of the majority of synapses or even lacks synapses altogether. This surprising resilience of synaptic structure might be explained by a high redundancy between different SCAMs, by the assumption that the crucial molecular players in synapse structure have yet to be discovered or by a grand variability in the mechanisms of synapse formation that underlies the diversity of synapses. Whatever the final answer turns out to be, the genetic dissection of the SCAM superfamilies has led to a much better understanding of the different steps required to form, differentiate and modify a synapse.
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Abe K, Chisaka O, Van Roy F, Takeichi M (2004) Stability of dendritic spines and synaptic contacts is controlled by alpha N-catenin. Nat Neurosci 7:357–363
Aberle H, Haghighi AP, Fetter RD, McCabe BD, Magalhaes TR, Goodman CS (2002) Wishful thinking encodes a BMP type II receptor that regulates synaptic growth in Drosophila. Neuron 33:545–558
Ackley BD, Jin Y (2004) Genetic analysis of synaptic target recognition and assembly. Trends Neurosci 27:540–547
Akins MR, Biederer T (2006) Cell-cell interactions in synaptogenesis. Curr Opin Neurobiol 16:83–89
Allan DW, St Pierre SE, Miguel-Aliaga I, Thor S (2003) Specification of neuropeptide cell identity by the integration of retrograde BMP signaling and a combinatorial transcription factor code. Cell 113:73–86
Arikawa-Hirasawa E, Le AH, Nishino I, Nonaka I, Ho NC, Francomano CA, Govindraj P, Hassell JR, Devaney JM, Spranger J, Stevenson RE, Iannaccone S, Dalakas MC, Yamada Y (2002a) Structural and functional mutations of the perlecan gene cause Schwartz-Jampel syndrome, with myotonic myopathy and chondrodysplasia. Am J Hum Genet 70:1368–1375
Arikawa-Hirasawa E, Rossi SG, Rotundo RL, Yamada Y (2002b) Absence of acetylcholinesterase at the neuromuscular junctions of perlecan-null mice. Nat Neurosci 5:119–123
Armstrong JN, Saganich MJ, Xu NJ, Henkemeyer M, Heinemann SF, Contractor A (2006) B-ephrin reverse signaling is required for NMDA-independent long-term potentiation of mossy fibers in the hippocampus. J Neurosci 26:3474–3481
Arndt K, Redies C (1996) Restricted expression of R-cadherin by brain nuclei and neural circuits of the developing chicken brain. J Comp Neurol 373:373–399
Augustin I, Rosenmund C, Sudhof TC, Brose N (1999) Munc13-1 is essential for fusion competence of glutamatergic synaptic vesicles. Nature 400:457–461
Bagri A, Cheng HJ, Yaron A, Pleasure SJ, Tessier-Lavigne M (2003) Stereotyped pruning of long hippocampal axon branches triggered by retraction inducers of the semaphorin family. Cell 113:285–299
Baines RA, Seugnet L, Thompson A, Salvaterra PM, Bate M (2002) Regulation of synaptic connectivity: levels of fasciclin II influence synaptic growth in the Drosophila CNS. J Neurosci 22:6587–6595
Baker NE (1988) Localization of transcripts from the wingless gene in whole Drosophila embryos. Development 103:289–298
Bamji SX, Shimazu K, Kimes N, Huelsken J, Birchmeier W, Lu B, Reichardt LF (2003) Role of beta-catenin in synaptic vesicle localization and presynaptic assembly. Neuron 40:719–731
Banker BQ, Hirst NS, Chester CS, Fok RY (1979) Histometric and electron cytochemical study of muscle in the dystrophic mouse. Ann N Y Acad Sci 317:115–131
Barbas JA, Chaix JC, Steinmetz M, Goridis C (1988) Differential splicing and alternative polyadenylation generates distinct NCAM transcripts and proteins in the mouse. EMBO J 7:625–632
Behar O, Golden JA, Mashimo H, Schoen FJ, Fishman MC (1996) Semaphorin III is needed for normal patterning and growth of nerves, bones and heart. Nature 383:525–528
Ben-Ari Y, Khazipov R, Leinekugel X, Caillard O, Gaiarsa JL (1997) GABAA, NMDA and AMPA receptors: a developmentally regulated ‘menage a trois’. Trends Neurosci 20:523–529
Benson DL, Tanaka H (1998) N-cadherin redistribution during synaptogenesis in hippocampal neurons. J Neurosci 18:6892–6904
Benson DL, Colman DR, Huntley GW (2001) Molecules, maps and synapse specificity. Nat Rev Neurosci 2:899–909
Biederer T, Sudhof TC (2000) Mints as adaptors. Direct binding to neurexins and recruitment of munc18. J Biol Chem 275:39803–39806
Biederer T, Sara Y, Mozhayeva M, Atasoy D, Liu X, Kavalali ET, Sudhof TC (2002) SynCAM, a synaptic adhesion molecule that drives synapse assembly. Science 297:1525–1531
Bouchard MJ, Dong Y, McDermott BM Jr, Lam DH, Brown KR, Shelanski M, Bellve AR, Racaniello VR (2000) Defects in nuclear and cytoskeletal morphology and mitochondrial localization in spermatozoa of mice lacking nectin-2, a component of cell-cell adherens junctions. Mol Cell Biol 20:2865–2873
Boucard AA, Chubykin AA, Comoletti D, Taylor P, Sudhof TC (2005) A splice code for trans-synaptic cell adhesion mediated by binding of neuroligin 1 to alpha- and beta-neurexins. Neuron 48:229–236
Bourgeois JP, Rakic P (1993) Changes of synaptic density in the primary visual cortex of the macaque monkey from fetal to adult stage. J Neurosci 13:2801–2820
Bozdagi O, Shan W, Tanaka H, Benson DL, Huntley GW (2000) Increasing numbers of synaptic puncta during late-phase LTP: N-cadherin is synthesized, recruited to synaptic sites, and required for potentiation. Neuron 28:245–259
Bresler T, Shapira M, Boeckers T, Dresbach T, Futter M, Garner CC, Rosenblum K, Gundelfinger ED, Ziv NE (2004) Postsynaptic density assembly is fundamentally different from presynaptic active zone assembly. J Neurosci 24:1507–1520
Brionne TC, Tesseur I, Masliah E, Wyss-Coray T (2003) Loss of TGF-beta 1 leads to increased neuronal cell death and microgliosis in mouse brain. Neuron 40:1133–1145
Bukalo O, Fentrop N, Lee AY, Salmen B, Law JW, Wotjak CT, Schweizer M, Dityatev A, Schachner M (2004) Conditional ablation of the neural cell adhesion molecule reduces precision of spatial learning, long-term potentiation, and depression in the CA1 subfield of mouse hippocampus. J Neurosci 24:1565–1577
Bulow HE, Hobert O (2004) Differential sulfations and epimerization define heparan sulfate specificity in nervous system development. Neuron 41:723–736
Butz S, Okamoto M, Sudhof TC (1998) A tripartite protein complex with the potential to couple synaptic vesicle exocytosis to cell adhesion in brain. Cell 94:773–782
Cano-Gauci DF, Song HH, Yang H, McKerlie C, Choo B, Shi W, Pullano R, Piscione TD, Grisaru S, Soon S, Sedlackova L, Tanswell AK, Mak TW, Yeger H, Lockwood GA, Rosenblum ND, Filmus J (1999) Glypican-3-deficient mice exhibit developmental overgrowth and some of the abnormalities typical of Simpson-Golabi-Behmel syndrome. J Cell Biol 146:255–264
Carbonetto S (1977) Neuromuscular transmission in dystrophic mice. J Neurophysiol 40:836–843
Carroll P, Gayet O, Feuillet C, Kallenbach S, Bovis B de, Dudley K, Alonso S (2001) Juxtaposition of CNR protocadherins and reelin expression in the developing spinal cord. Mol Cell Neurosci 17:611–623
Catalano SM, Messersmith EK, Goodman CS, Shatz CJ, Chedotal A (1998) Many major CNS axon projections develop normally in the absence of semaphorin III. Mol Cell Neurosci 11:173–182
Chen H, Bagri A, Zupicich JA, Zou Y, Stoeckli E, Pleasure SJ, Lowenstein DH, Skarnes WC, Chedotal A, Tessier-Lavigne M (2000) Neuropilin-2 regulates the development of selective cranial and sensory nerves and hippocampal mossy fiber projections. Neuron 25:43–56
Cheng HJ, Bagri A, Yaron A, Stein E, Pleasure SJ, Tessier-Lavigne M (2001) Plexin-A3 mediates semaphorin signaling and regulates the development of hippocampal axonal projections. Neuron 32:249–263
Chih B, Engelman H, Scheiffele P (2005) Control of excitatory and inhibitory synapse formation by neuroligins. Science 307:1324–1328
Ciani L, Salinas PC (2005) WNTs in the vertebrate nervous system: from patterning to neuronal connectivity. Nat Rev Neurosci 6:351–362
Cloutier JF, Sahay A, Chang EC, Tessier-Lavigne M, Dulac C, Kolodkin AL, Ginty DD (2004) Differential requirements for semaphorin 3F and slit-1 in axonal targeting, fasciculation, and segregation of olfactory sensory neuron projections. J Neurosci 24:9087–9096
Cocchi F, Menotti L, Mirandola P, Lopez M, Campadelli-Fiume G (1998) The ectodomain of a novel member of the immunoglobulin subfamily related to the poliovirus receptor has the attributes of a bona fide receptor for Herpes simplex virus types 1 and 2 in human cells. J Virol 72:9992–10002
Cohen NR, Taylor JS, Scott LB, Guillery RW, Soriano P, Furley AJ (1998) Errors in corticospinal axon guidance in mice lacking the neural cell adhesion molecule L1. Curr Biol 8:26–33
Colognato H, Yurchenco PD (2000) Form and function: the laminin family of heterotrimers. Dev Dyn 218:213–234
Craig AM, Boudin H (2001) Molecular heterogeneity of central synapses: afferent and target regulation. Nat Neurosci 4:569–578
Craig AM, Graf ER, Linhoff MW (2006) How to build a central synapse: clues from cell culture. Trends Neurosci 29:8–20
Cremer H, Lange R, Christoph A, Plomann M, Vopper G, Roes J, Brown R, Baldwin S, Kraemer P, Scheff S, et al (1994) Inactivation of the N-CAM gene in mice results in size reduction of the olfactory bulb and deficits in spatial learning. Nature 367:455–459
Cremer H, Chazal G, Goridis C, Represa A (1997) NCAM is essential for axonal growth and fasciculation in the hippocampus. Mol Cell Neurosci 8:323–335
Cremer H, Chazal G, Carleton A, Goridis C, Vincent JD, Lledo PM (1998) Long-term but not short-term plasticity at mossy fiber synapses is impaired in neural cell adhesion molecule-deficient mice. Proc Natl Acad Sci USA 95:13242–13247
Dahme M, Bartsch U, Martini R, Anliker B, Schachner M, Mantei N (1997) Disruption of the mouse L1 gene leads to malformations of the nervous system. Nat Genet 17:346–349
Davis GW, Schuster CM, Goodman CS (1997) Genetic analysis of the mechanisms controlling target selection: target-derived fasciclin II regulates the pattern of synapse formation. Neuron 19:561–573
Davy A, Soriano P (2005) Ephrin signaling in vivo: look both ways. Dev Dyn 232:1–10
Dean C, Dresbach T (2006) Neuroligins and neurexins: linking cell adhesion, synapse formation and cognitive function. Trends Neurosci 29:21–29
Dean C, Scholl FG, Choih J, DeMaria S, Berger J, Isacoff E, Scheiffele P (2003) Neurexin mediates the assembly of presynaptic terminals. Nat Neurosci 6:708–716
Demyanenko GP, Tsai AY, Maness PF (1999) Abnormalities in neuronal process extension, hippocampal development, and the ventricular system of L1 knockout mice. J Neurosci 19:4907–4920
Demyanenko GP, Shibata Y, Maness PF (2001) Altered distribution of dopaminergic neurons in the brain of L1 null mice. Brain Res Dev Brain Res 126:21–30
Dityatev A, Dityateva G, Schachner M (2000) Synaptic strength as a function of post- versus presynaptic expression of the neural cell adhesion molecule NCAM. Neuron 26:207–217
Dityatev A, Dityateva G, Sytnyk V, Delling M, Toni N, Nikonenko I, Muller D, Schachner M (2004) Polysialylated neural cell adhesion molecule promotes remodeling and formation of hippocampal synapses. J Neurosci 24:9372–9382
Drees F, Pokutta S, Yamada S, Nelson WJ, Weis WI (2005) Alpha-catenin is a molecular switch that binds E-cadherin-beta-catenin and regulates actin-filament assembly. Cell 123:903–915
Dresbach T, Neeb A, Meyer G, Gundelfinger ED, Brose N (2004) Synaptic targeting of neuroligin is independent of neurexin and SAP90/PSD95 binding. Mol Cell Neurosci 27:227–235
Egea J, Nissen UV, Dufour A, Sahin M, Greer P, Kullander K, Mrsic-Flogel TD, Greenberg ME, Kiehn O, Vanderhaeghen P, Klein R (2005) Regulation of EphA 4 kinase activity is required for a subset of axon guidance decisions suggesting a key role for receptor clustering in Eph function. Neuron 47:515–528
Elowe S, Holland SJ, Kulkarni S, Pawson T (2001) Downregulation of the Ras-mitogen-activated protein kinase pathway by the EphB2 receptor tyrosine kinase is required for ephrin-induced neurite retraction. Mol Cell Biol 21:7429–7441
Elste AM, Benson DL (2006) Structural basis for developmentally regulated changes in cadherin function at synapses. J Comp Neurol 495:324–335
Erdmann B, Kirsch FP, Rathjen FG, More MI (2003) N-cadherin is essential for retinal lamination in the zebrafish. Dev Dyn 226:570–577
Esko JD, Lindahl U (2001) Molecular diversity of heparan sulfate. J Clin Invest 108:169–173
Ethell IM, Yamaguchi Y (1999) Cell surface heparan sulfate proteoglycan syndecan-2 induces the maturation of dendritic spines in rat hippocampal neurons. J Cell Biol 144:575–586
Fairless R, Reissner C, Missler M (2006) The role of neuroligin binding to neurexins in synaptic organization. In: Dityatev A, El-Husseini A (eds) Molecular mechanisms of synaptogenesis. Springer, Berlin Heidelberg New York, pp 111–124
Falk J, Bechara A, Fiore R, Nawabi H, Zhou H, Hoyo-Becerra C, Bozon M, Rougon G, Grumet M, Puschel AW, Sanes JR, Castellani V (2005) Dual functional activity of semaphorin 3B is required for positioning the anterior commissure. Neuron 48:63–75
Fannon AM, Colman DR (1996) A model for central synaptic junctional complex formation based on the differential adhesive specificities of the cadherins. Neuron 17:423–434
Feiner L, Webber AL, Brown CB, Lu MM, Jia L, Feinstein P, Mombaerts P, Epstein JA, Raper JA (2001) Targeted disruption of semaphorin 3C leads to persistent truncus arteriosus and aortic arch interruption. Development 128:3061–3070
Fenstermaker V, Chen Y, Ghosh A, Yuste R (2004) Regulation of dendritic length and branching by semaphorin 3A. J Neurobiol 58:403–412
Flavell SW, Cowan CW, Kim TK, Greer PL, Lin Y, Paradis S, Griffith EC, Hu LS, Chen C, Greenberg ME (2006) Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number. Science 311:1008–1012
Fransen E, D’Hooge R, Van Camp G, Verhoye M, Sijbers J, Reyniers E, Soriano P, Kamiguchi H, Willemsen R, Koekkoek SK, De Zeeuw CI, De Deyn PP, Van der Linden A, Lemmon V, Kooy RF, Willems PJ (1998) L1 knockout mice show dilated ventricles, vermis hypoplasia and impaired exploration patterns. Hum Mol Genet 7:999–1009
Fu Z, Washbourne P, Ortinski P, Vicini S (2003) Functional excitatory synapses in HEK293 cells expressing neuroligin and glutamate receptors. J Neurophysiol 90:3950–3957
Fujita E, Kouroku Y, Ozeki S, Tanabe Y, Toyama Y, Maekawa M, Kojima N, Senoo H, Toshimori K, Momoi T (2006) Oligo-astheno-teratozoospermia in mice lacking RA175/TSLC1/SynCAM/IGSF4A, a cell adhesion molecule in the immunoglobulin superfamily. Mol Cell Biol 26:718–726
Gautam M, Noakes PG, Moscoso L, Rupp F, Scheller RH, Merlie JP, Sanes JR (1996) Defective neuromuscular synaptogenesis in agrin-deficient mutant mice. Cell 85:525–535
Geppert M, Khvotchev M, Krasnoperov V, Goda Y, Missler M, Hammer RE, Ichtchenko K, Petrenko AG, Sudhof TC (1998) Neurexin I alpha is a major alpha-latrotoxin receptor that cooperates in alpha-latrotoxin action. J Biol Chem 273:1705–1710
Gerrow K, Romorini S, Nabi SM, Colicos MA, Sala C, El-Husseini A (2006) A preformed complex of postsynaptic proteins is involved in excitatory synapse development. Neuron 49:547–562
Giger RJ, Cloutier JF, Sahay A, Prinjha RK, Levengood DV, Moore SE, Pickering S, Simmons D, Rastan S, Walsh FS, Kolodkin AL, Ginty DD, Geppert M (2000) Neuropilin-2 is required in vivo for selective axon guidance responses to secreted semaphorins. Neuron 25:29–41
Godenschwege TA, Hu H, Shan-Crofts X, Goodman CS, Murphey RK (2002) Bi-directional signaling by semaphorin 1a during central synapse formation in Drosophila. Nat Neurosci 5:1294–1301
Goodman CS (1996) Mechanisms and molecules that control growth cone guidance. Annu Rev Neurosci 19:341–377
Graf ER, Zhang X, Jin SX, Linhoff MW, Craig AM (2004) Neurexins induce differentiation of GABA and glutamate postsynaptic specializations via neuroligins. Cell 119:1013–1026
Graf ER, Kang Y, Hauner AM, Craig AM (2006) Structure function and splice site analysis of the synaptogenic activity of the neurexin-1 beta LNS domain. J Neurosci 26:4256–4265
Grobe K, Inatani M, Pallerla SR, Castagnola J, Yamaguchi Y, Esko JD (2005) Cerebral hypoplasia and craniofacial defects in mice lacking heparan sulfate Ndst1 gene function. Development 132:3777–3786
Grunwald IC, Korte M, Wolfer D, Wilkinson GA, Unsicker K, Lipp HP, Bonhoeffer T, Klein R (2001) Kinase-independent requirement of EphB2 receptors in hippocampal synaptic plasticity. Neuron 32:1027–1040
Hall AC, Lucas FR, Salinas PC (2000) Axonal remodeling and synaptic differentiation in the cerebellum is regulated by WNT-7a signaling. Cell 100:525–535
Hata Y, Butz S, Sudhof TC (1996) CASK: a novel dlg/PSD95 homolog with an N-terminal calmodulin-dependent protein kinase domain identified by interaction with neurexins. J Neurosci 16:2488–2494
Hayashi K, Kaufman L, Ross MD, Klotman PE (2005) Definition of the critical domains required for homophilic targeting of mouse sidekick molecules. FASEB J 19:614–616
Henderson JT, Georgiou J, Jia Z, Robertson J, Elowe S, Roder JC, Pawson T (2001) The receptor tyrosine kinase EphB2 regulates NMDA-dependent synaptic function. Neuron 32:1041–1056
Henkemeyer M, Itkis OS, Ngo M, Hickmott PW, Ethell IM (2003) Multiple EphB receptor tyrosine kinases shape dendritic spines in the hippocampus. J Cell Biol 163:1313–1326
Herrenknecht K, Ozawa M, Eckerskorn C, Lottspeich F, Lenter M, Kemler R (1991) The uvomorulin-anchorage protein alpha catenin is a vinculin homologue. Proc Natl Acad Sci USA 88:9156–9160
Himanen JP, Chumley MJ, Lackmann M, Li C, Barton WA, Jeffrey PD, Vearing C, Geleick D, Feldheim DA, Boyd AW, Henkemeyer M, Nikolov DB (2004) Repelling class discrimination: ephrin-A5 binds to and activates EphB2 receptor signaling. Nat Neurosci 7:501–509
Hinck L, Nathke IS, Papkoff J, Nelson WJ (1994) Dynamics of cadherin/catenin complex formation: novel protein interactions and pathways of complex assembly. J Cell Biol 125:1327–1340
Honda T, Sakisaka T, Yamada T, Kumazawa N, Hoshino T, Kajita M, Kayahara T, Ishizaki H, Tanaka-Okamoto M, Mizoguchi A, Manabe T, Miyoshi J, Takai Y (2006) Involvement of nectins in the formation of puncta adherentia junctions and the mossy fiber trajectory in the mouse hippocampus. Mol Cell Neurosci 31:315–325
Huber AH, Weis WI (2001) The structure of the beta-catenin/E-cadherin complex and the molecular basis of diverse ligand recognition by beta-catenin. Cell 105:391–402
Huber AB, Kolodkin AL, Ginty DD, Cloutier JF (2003) Signaling at the growth cone: ligand-receptor complexes and the control of axon growth and guidance. Annu Rev Neurosci 26:509–563
Ichtchenko K, Hata Y, Nguyen T, Ullrich B, Missler M, Moomaw C, Sudhof TC (1995) Neuroligin 1: a splice site-specific ligand for beta-neurexins. Cell 81:435–443
Ichtchenko K, Nguyen T, Sudhof TC (1996) Structures, alternative splicing, and neurexin binding of multiple neuroligins. J Biol Chem 271:2676–2682
Ikeda W, Nakanishi H, Miyoshi J, Mandai K, Ishizaki H, Tanaka M, Togawa A, Takahashi K, Nishioka H, Yoshida H, Mizoguchi A, Nishikawa S, Takai Y (1999) Afadin: a key molecule essential for structural organization of cell-cell junctions of polarized epithelia during embryogenesis. J Cell Biol 146:1117–1132
Inagaki S, Ohoka Y, Sugimoto H, Fujioka S, Amazaki M, Kurinami H, Miyazaki N, Tohyama M, Furuyama T (2001) Sema4c, a transmembrane semaphorin, interacts with a post-synaptic density protein, PSD-95. J Biol Chem 276:9174–9181
Inoue T, Tanaka T, Suzuki SC, Takeichi M (1998) Cadherin-6 in the developing mouse brain: expression along restricted connection systems and synaptic localization suggest a potential role in neuronal circuitry. Dev Dyn 211:338–351
Irie M, Hata Y, Takeuchi M, Ichtchenko K, Toyoda A, Hirao K, Takai Y, Rosahl TW, Sudhof TC (1997) Binding of neuroligins to PSD-95. Science 277:1511–1515
Israely I, Costa RM, Xie CW, Silva AJ, Kosik KS, Liu X (2004) Deletion of the neuron-specific protein delta-catenin leads to severe cognitive and synaptic dysfunction. Curr Biol 14:1657–1663
Jin Y (2002) Synaptogenesis: insights from worm and fly. Curr Opin Neurobiol 12:71–79
Jones N, Blasutig IM, Eremina V, Ruston JM, Bladt F, Li H, Huang H, Larose L, Li SS, Takano T, Quaggin SE, Pawson T (2006) Nck adaptor proteins link nephrin to the actin cytoskeleton of kidney podocytes. Nature 440:818–823
Jontes JD, Emond MR, Smith SJ (2004) In vivo trafficking and targeting of N-cadherin to nascent presynaptic terminals. J Neurosci 24:9027–9034
Kaksonen M, Pavlov I, Voikar V, Lauri SE, Hienola A, Riekki R, Lakso M, Taira T, Rauvala H (2002) Syndecan-3-deficient mice exhibit enhanced LTP and impaired hippocampus-dependent memory. Mol Cell Neurosci 21:158–172
Kakunaga S, Ikeda W, Itoh S, Deguchi-Tawarada M, Ohtsuka T, Mizoguchi A, Takai Y (2005) Nectin-like molecule-1/TSLL1/SynCAM3: a neural tissue-specific immunoglobulin-like cell-cell adhesion molecule localizing at non-junctional contact sites of presynaptic nerve terminals, axons and glia cell processes. J Cell Sci 118:1267–1277
Kamiguchi H, Hlavin ML, Lemmon V (1998a) Role of L1 in neural development: what the knockouts tell us. Mol Cell Neurosci 12:48–55
Kamiguchi H, Hlavin ML, Yamasaki M, Lemmon V (1998b) Adhesion molecules and inherited diseases of the human nervous system. Annu Rev Neurosci 21:97–125
Kattenstroth G, Tantalaki E, Sudhof TC, Gottmann K, Missler M (2004) Postsynaptic N-methyl-D-aspartate receptor function requires alpha-neurexins. Proc Natl Acad Sci USA 101:2607–2612
Katz LC, Shatz CJ (1996) Synaptic activity and the construction of cortical circuits. Science 274:1133–1138
Keshishian H, Kim YS (2004) Orchestrating development and function: retrograde BMP signaling in the Drosophila nervous system. Trends Neurosci 27:143–147
Kim SH, Yamamoto A, Bouwmeester T, Agius E, Robertis EM (1998) The role of paraxial protocadherin in selective adhesion and cell movements of the mesoderm during Xenopus gastrulation. Development 125:4681–4690
Kiss JZ, Rougon G (1997) Cell biology of polysialic acid. Curr Opin Neurobiol 7:640–646
Kitsukawa T, Shimizu M, Sanbo M, Hirata T, Taniguchi M, Bekku Y, Yagi T, Fujisawa H (1997) Neuropilin-semaphorin III/D-mediated chemorepulsive signals play a crucial role in peripheral nerve projection in mice. Neuron 19:995–1005
Knight D, Tolley LK, Kim DK, Lavidis NA, Noakes PG (2003) Functional analysis of neurotransmission at beta2-laminin deficient terminals. J Physiol (Lond) 546:789–800
Ko J, Kim S, Chung HS, Kim K, Han K, Kim H, Jun H, Kaang B-K, Kim E (2006) SALM synaptic cell adhesion-like molecules regulate the differentiation of excitatory synapses. Neuron 50:233
Kohmura N, Senzaki K, Hamada S, Kai N, Yasuda R, Watanabe M, Ishii H, Yasuda M, Mishina M, Yagi T (1998) Diversity revealed by a novel family of cadherins expressed in neurons at a synaptic complex. Neuron 20:1137–1151
Kolodkin AL, Matthes DJ, O’Connor TP, Patel NH, Admon A, Bentley D, Goodman CS (1992) Fasciclin IV: sequence, expression, and function during growth cone guidance in the grasshopper embryo. Neuron 9:831–845
Kolodkin AL, Matthes DJ, Goodman CS (1993) The semaphorin genes encode a family of transmembrane and secreted growth cone guidance molecules. Cell 75:1389–1399
Kostetskii I, Moore R, Kemler R, Radice GL (2001) Differential adhesion leads to segregation and exclusion of N-cadherin-deficient cells in chimeric embryos. Dev Biol 234:72–79
Kullander K, Klein R (2002) Mechanisms and functions of Eph and ephrin signalling. Nat Rev Mol Cell Biol 3:475–486
Kuroda H, Inui M, Sugimoto K, Hayata T, Asashima M (2002) Axial protocadherin is a mediator of prenotochord cell sorting in Xenopus. Dev Biol 244:267–277
Larue L, Ohsugi M, Hirchenhain J, Kemler R (1994) E-cadherin null mutant embryos fail to form a trophectoderm epithelium. Proc Natl Acad Sci USA 91:8263–8267
Law JW, Lee AY, Sun M, Nikonenko AG, Chung SK, Dityatev A, Schachner M, Morellini F (2003) Decreased anxiety, altered place learning, and increased CA1 basal excitatory synaptic transmission in mice with conditional ablation of the neural cell adhesion molecule L1. J Neurosci 23:10419–10432
Lee JS, Chien CB (2004) When sugars guide axons: insights from heparan sulphate proteoglycan mutants. Nat Rev Genet 5:923–935
Leighton PA, Mitchell KJ, Goodrich LV, Lu X, Pinson K, Scherz P, Skarnes WC, Tessier-Lavigne M (2001) Defining brain wiring patterns and mechanisms through gene trapping in mice. Nature 410:174–179
Lele Z, Folchert A, Concha M, Rauch GJ, Geisler R, Rosa F, Wilson SW, Hammerschmidt M, Bally-Cuif L (2002) Parachute/n-cadherin is required for morphogenesis and maintained integrity of the zebrafish neural tube. Development 129:3281–3294
Lemmon V, Farr KL, Lagenaur C (1989) L1-mediated axon outgrowth occurs via a homophilic binding mechanism. Neuron 2:1597–1603
Levinson JN, Chery N, Huang K, Wong TP, Gerrow K, Kang R, Prange O, Wang YT, El-Husseini A (2005) Neuroligins mediate excitatory and inhibitory synapse formation: involvement of PSD-95 and neurexin-1beta in neuroligin-induced synaptic specificity. J Biol Chem 280:17312–17319
Lin DM, Fetter RD, Kopczynski C, Grenningloh G, Goodman CS (1994) Genetic analysis of fasciclin II in Drosophila: defasciculation, refasciculation, and altered fasciculation. Neuron 13:1055–1069
Lucas FR, Salinas PC (1997) WNT-7a induces axonal remodeling and increases synapsin I levels in cerebellar neurons. Dev Biol 192:31–44
Lucas FR, Goold RG, Gordon-Weeks PR, Salinas PC (1998) Inhibition of GSK-3beta leading to the loss of phosphorylated MAP-1B is an early event in axonal remodelling induced by WNT-7a or lithium. J Cell Sci 111:1351–1361
Luo Y, Raible D, Raper JA (1993) Collapsin: a protein in brain that induces the collapse and paralysis of neuronal growth cones. Cell 75:217–227
Luo Y, Ferreira-Cornwell M, Baldwin H, Kostetskii I, Lenox J, Lieberman M, Radice G (2001) Rescuing the N-cadherin knockout by cardiac-specific expression of N- or E-cadherin. Development 128:459–469
Manabe T, Togashi H, Uchida N, Suzuki SC, Hayakawa Y, Yamamoto M, Yoda H, Miyakawa T, Takeichi M, Chisaka O (2000) Loss of cadherin-11 adhesion receptor enhances plastic changes in hippocampal synapses and modifies behavioral responses. Mol Cell Neurosci 15:534–546
Mandai K, Nakanishi H, Satoh A, Obaishi H, Wada M, Nishioka H, Itoh M, Mizoguchi A, Aoki T, Fujimoto T, Matsuda Y, Tsukita S, Takai Y (1997) Afadin: a novel actin filament-binding protein with one PDZ domain localized at cadherin-based cell-to-cell adherens junction. J Cell Biol 139:517–528
Marques G, Bao H, Haerry TE, Shimell MJ, Duchek P, Zhang B, O'Connor MB (2002) The Drosophila BMP type II receptor wishful thinking regulates neuromuscular synapse morphology and function. Neuron 33:529–543
Marques G, Haerry TE, Crotty ML, Xue M, Zhang B, O’Connor MB (2003) Retrograde Gbb signaling through the Bmp type 2 receptor wishful thinking regulates systemic FMRFa expression in Drosophila. Development 130:5457–5470
Massague J (1998) TGF-beta signal transduction. Annu Rev Biochem 67:753–791
Massague J (2000) How cells read TGF-beta signals. Nat Rev Mol Cell Biol 1:169–178
Matthes DJ, Sink H, Kolodkin AL, Goodman CS (1995) Semaphorin II can function as a selective inhibitor of specific synaptic arborizations. Cell 81:631–639
McCabe BD, Marques G, Haghighi AP, Fetter RD, Crotty ML, Haerry TE, Goodman CS, O’Connor MB (2003) The BMP homolog Gbb provides a retrograde signal that regulates synaptic growth at the Drosophila neuromuscular junction. Neuron 39:241–254
McCabe BD, Hom S, Aberle H, Fetter RD, Marques G, Haerry TE, Wan H, O’Connor MB, Goodman CS, Haghighi AP (2004) Highwire regulates presynaptic BMP signaling essential for synaptic growth. Neuron 41:891–905
McLennan IS, Koishi K (1994) Transforming growth factor-beta-2 (TGF-beta 2) is associated with mature rat neuromuscular junctions. Neurosci Lett 177:151–154
Messersmith EK, Leonardo ED, Shatz CJ, Tessier-Lavigne M, Goodman CS, Kolodkin AL (1995) Semaphorin III can function as a selective chemorepellent to pattern sensory projections in the spinal cord. Neuron 14:949–959
Miner JH, Cunningham J, Sanes JR (1998) Roles for laminin in embryogenesis: exencephaly, syndactyly, and placentopathy in mice lacking the laminin alpha5 chain. J Cell Biol 143:1713–1723
Miskevich F, Zhu Y, Ranscht B, Sanes JR (1998) Expression of multiple cadherins and catenins in the chick optic tectum. Mol Cell Neurosci 12:240–255
Missler M (2003) Synaptic cell adhesion goes functional. Trends Neurosci 26:176–178
Missler M, Sudhof TC (1998) Neurexins: three genes and 1001 products. Trends Genet 14:20–26
Missler M, Wolff A, Merker HJ, Wolff JR (1993) Pre- and postnatal development of the primary visual cortex of the common marmoset. II. Formation, remodelling, and elimination of synapses as overlapping processes. J Comp Neurol 333:53–67
Missler M, Zhang W, Rohlmann A, Kattenstroth G, Hammer RE, Gottmann K, Sudhof TC (2003) Alpha-neurexins couple Ca2+ channels to synaptic vesicle exocytosis. Nature 423:939–948
Miyahara M, Nakanishi H, Takahashi K, Satoh-Horikawa K, Tachibana K, Takai Y (2000) Interaction of nectin with afadin is necessary for its clustering at cell-cell contact sites but not for its cis dimerization or trans interaction. J Biol Chem 275:613–618
Miyatani S, Shimamura K, Hatta M, Nagafuchi A, Nose A, Matsunaga M, Hatta K, Takeichi M (1989) Neural cadherin: role in selective cell-cell adhesion. Science 245:631–635
Mizoguchi A, Nakanishi H, Kimura K, Matsubara K, Ozaki-Kuroda K, Katata T, Honda T, Kiyohara Y, Heo K, Higashi M, Tsutsumi T, Sonoda S, Ide C, Takai Y (2002) Nectin: an adhesion molecule involved in formation of synapses. J Cell Biol 156:555–565
Muller D, Wang C, Skibo G, Toni N, Cremer H, Calaora V, Rougon G, Kiss JZ (1996) PSA-NCAM is required for activity-induced synaptic plasticity. Neuron 17:413–422
Murata Y, Hamada S, Morishita H, Mutoh T, Yagi T (2004) Interaction with protocadherin-gamma regulates the cell surface expression of protocadherin-alpha. J Biol Chem 279:49508–49516
Nam CI, Chen L (2005) Postsynaptic assembly induced by neurexin-neuroligin interaction and neurotransmitter. Proc Natl Acad Sci USA 102:6137–6142
Nguyen T, Sudhof TC (1997) Binding properties of neuroligin 1 and neurexin 1beta reveal function as heterophilic cell adhesion molecules. J Biol Chem 272:26032–26039
Nguyen DN, Liu Y, Litsky ML, Reinke R (1997) The sidekick gene, a member of the immunoglobulin superfamily, is required for pattern formation in the Drosophila eye. Development 124:3303–3312
Niethammer P, Delling M, Sytnyk V, Dityatev A, Fukami K, Schachner M (2002) Cosignaling of NCAM via lipid rafts and the FGF receptor is required for neuritogenesis. J Cell Biol 157:521–532
Nishimune H, Sanes JR, Carlson SS (2004) A synaptic laminin-calcium channel interaction organizes active zones in motor nerve terminals. Nature 432:580–587
Noakes PG, Gautam M, Mudd J, Sanes JR, Merlie JP (1995) Aberrant differentiation of neuromuscular junctions in mice lacking s-laminin/laminin beta 2. Nature 374:258–262
Obata S, Sago H, Mori N, Rochelle JM, Seldin MF, Davidson M, St John T, Taketani S, Suzuki ST (1995) Protocadherin Pcdh2 shows properties similar to, but distinct from, those of classical cadherins. J Cell Sci 108:3765–3773
Obst-Pernberg K, Redies C (1999) Cadherins and synaptic specificity. J Neurosci Res 58:130–138
Packard M, Koo ES, Gorczyca M, Sharpe J, Cumberledge S, Budnik V (2002) The Drosophila Wnt, wingless, provides an essential signal for pre- and postsynaptic differentiation. Cell 111:319–330
Packard M, Mathew D, Budnik V (2003) Wnts and TGF beta in synaptogenesis: old friends signalling at new places. Nat Rev Neurosci 4:113–120
Pasterkamp RJ, Peschon JJ, Spriggs MK, Kolodkin AL (2003) Semaphorin 7A promotes axon outgrowth through integrins and MAPKs. Nature 424:398–405
Patton BL (2000) Laminins of the neuromuscular system. Microsc Res Tech 51:247–261
Patton BL, Miner JH, Chiu AY, Sanes JR (1997) Distribution and function of laminins in the neuromuscular system of developing, adult, and mutant mice. J Cell Biol 139:1507–1521
Patton BL, Cunningham JM, Thyboll J, Kortesmaa J, Westerblad H, Edstrom L, Tryggvason K, Sanes JR (2001) Properly formed but improperly localized synaptic specializations in the absence of laminin alpha4. Nat Neurosci 4:597–604
Persohn E, Schachner M (1990) Immunohistological localization of the neural adhesion molecules L1 and N-CAM in the developing hippocampus of the mouse. J Neurocytol 19:807–819
Persohn E, Pollerberg GE, Schachner M (1989) Immunoelectron-microscopic localization of the 180 kD component of the neural cell adhesion molecule N-CAM in postsynaptic membranes. J Comp Neurol 288:92–100
Phillips GR, Tanaka H, Frank M, Elste A, Fidler L, Benson DL, Colman DR (2003) Gamma-protocadherins are targeted to subsets of synapses and intracellular organelles in neurons. J Neurosci 23:5096–5104
Pilia G, Hughes-Benzie RM, MacKenzie A, Baybayan P, Chen EY, Huber R, Neri G, Cao A, Forabosco A, Schlessinger D (1996) Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome. Nat Genet 12:241–247
Pokutta S, Weis WI (2000) Structure of the dimerization and beta-catenin-binding region of alpha-catenin. Mol Cell 5:533–543
Polleux F, Giger RJ, Ginty DD, Kolodkin AL, Ghosh A (1998) Patterning of cortical efferent projections by semaphorin-neuropilin interactions. Science 282:1904–1906
Polleux F, Morrow T, Ghosh A (2000) Semaphorin 3A is a chemoattractant for cortical apical dendrites. Nature 404:567–573
Polo-Parada L, Bose CM, Landmesser LT (2001) Alterations in transmission, vesicle dynamics, and transmitter release machinery at NCAM-deficient neuromuscular junctions. Neuron 32:815–828
Polo-Parada L, Bose CM, Plattner F, Landmesser LT (2004) Distinct roles of different neural cell adhesion molecule (NCAM) isoforms in synaptic maturation revealed by analysis of NCAM 180 kDa isoform-deficient mice. J Neurosci 24:1852–1864
Pozas E, Pascual M, Nguyen Ba-Charvet KT, Guijarro P, Sotelo C, Chedotal A, Del Rio JA, Soriano E (2001) Age-dependent effects of secreted semaphorins 3A, 3F, and 3E on developing hippocampal axons: in vitro effects and phenotype of semaphorin 3A(-/-) mice. Mol Cell Neurosci 18:26–43
Prange O, Wong TP, Gerrow K, Wang YT, El-Husseini A (2004) A balance between excitatory and inhibitory synapses is controlled by PSD-95 and neuroligin. Proc Natl Acad Sci USA 101:13915–13920
Puschel AW, Adams RH, Betz H (1996) The sensory innervation of the mouse spinal cord may be patterned by differential expression of and differential responsiveness to semaphorins. Mol Cell Neurosci 7:419–431
Putaala H, Soininen R, Kilpelainen P, Wartiovaara J, Tryggvason K (2001) The murine nephrin gene is specifically expressed in kidney, brain and pancreas: inactivation of the gene leads to massive proteinuria and neonatal death. Hum Mol Genet 10:1–8
Radice GL, Rayburn H, Matsunami H, Knudsen KA, Takeichi M, Hynes RO (1997) Developmental defects in mouse embryos lacking N-cadherin. Dev Biol 181:64–78
Rafuse VF, Polo-Parada L, Landmesser LT (2000) Structural and functional alterations of neuromuscular junctions in NCAM-deficient mice. J Neurosci 20:6529–6539
Ranscht B (2000) Cadherins: molecular codes for axon guidance and synapse formation. Int J Dev Neurosci 18:643–651
Raper JA (2000) Semaphorins and their receptors in vertebrates and invertebrates. Curr Opin Neurobiol 10:88–94
Rauch U (2004) Extracellular matrix components associated with remodeling processes in brain. Cell Mol Life Sci 61:2031–2045
Rawson JM, Lee M, Kennedy EL, Selleck SB (2003) Drosophila neuromuscular synapse assembly and function require the TGF-beta type I receptor saxophone and the transcription factor Mad. J Neurobiol 55:134–150
Redies C (2000) Cadherins in the central nervous system. Prog Neurobiol 61:611–648
Redies C, Engelhart K, Takeichi M (1993) Differential expression of N- and R-cadherin in functional neuronal systems and other structures of the developing chicken brain. J Comp Neurol 333:398–416
Reymond N, Fabre S, Lecocq E, Adelaide J, Dubreuil P, Lopez M (2001) Nectin4/PRR4, a new afadin-associated member of the nectin family that trans-interacts with nectin1/PRR1 through V domain interaction. J Biol Chem 276:43205–43215
Riethmacher D, Brinkmann V, Birchmeier C (1995) A targeted mutation in the mouse E-cadherin gene results in defective preimplantation development. Proc Natl Acad Sci USA 92:855–859
Rimm DL, Koslov ER, Kebriaei P, Cianci CD, Morrow JS (1995) Alpha 1(E)-catenin is an actin-binding and -bundling protein mediating the attachment of F-actin to the membrane adhesion complex. Proc Natl Acad Sci USA 92:8813–8817
Rosales CR, Osborne KD, Zuccarino GV, Scheiffele P, Silverman MA (2005) A cytoplasmic motif targets neuroligin-1 exclusively to dendrites of cultured hippocampal neurons. Eur J Neurosci 22:2381–2386
Rowen L, Young J, Birditt B, Kaur A, Madan A, Philipps DL, Qin S, Minx P, Wilson RK, Hood L, Graveley BR (2002) Analysis of the human neurexin genes: alternative splicing and the generation of protein diversity. Genomics 79:587–597
Rutishauser U, Landmesser L (1996) Polysialic acid in the vertebrate nervous system: a promoter of plasticity in cell-cell interactions. Trends Neurosci 19:422–427
Saghatelyan AK, Nikonenko AG, Sun M, Rolf B, Putthoff P, Kutsche M, Bartsch U, Dityatev A, Schachner M (2004) Reduced GABAergic transmission and number of hippocampal perisomatic inhibitory synapses in juvenile mice deficient in the neural cell adhesion molecule L1. Mol Cell Neurosci 26:191–203
Sahay A, Molliver ME, Ginty DD, Kolodkin AL (2003) Semaphorin 3F is critical for development of limbic system circuitry and is required in neurons for selective CNS axon guidance events. J Neurosci 23:6671–6680
Sahay A, Kim CH, Sepkuty JP, Cho E, Huganir RL, Ginty DD, Kolodkin AL (2005) Secreted semaphorins modulate synaptic transmission in the adult hippocampus. J Neurosci 25:3613–3620
Sakai JA, Halloran MC (2006) Semaphorin 3d guides laterality of retinal ganglion cell projections in zebrafish. Development 133:1035–1044
Salinas PC (2003) Synaptogenesis: Wnt and TGF-beta take centre stage. Curr Biol 13:R60–R62
Salinas PC (2005) Retrograde signalling at the synapse: a role for Wnt proteins. Biochem Soc Trans 33:1295–1298
Sano K, Tanihara H, Heimark RL, Obata S, Davidson M, St John T, Taketani S, Suzuki S (1993) Protocadherins: a large family of cadherin-related molecules in central nervous system. EMBO J 12:2249–2256
Sanyal S, Kim SM, Ramaswami M (2004) Retrograde regulation in the CNS; neuron-specific interpretations of TGF-beta signaling. Neuron 41:845–848
Sara Y, Biederer T, Atasoy D, Chubykin A, Mozhayeva MG, Sudhof TC, Kavalali ET (2005) Selective capability of SynCAM and neuroligin for functional synapse assembly. J Neurosci 25:260–270
Satoh-Horikawa K, Nakanishi H, Takahashi K, Miyahara M, Nishimura M, Tachibana K, Mizoguchi A, Takai Y (2000) Nectin-3, a new member of immunoglobulin-like cell adhesion molecules that shows homophilic and heterophilic cell-cell adhesion activities. J Biol Chem 275:10291–10299
Schachner M (1997) Neural recognition molecules and synaptic plasticity. Curr Opin Cell Biol 9:627–634
Scheiffele P (2003) Cell-cell signaling during synapse formation in the CNS. Annu Rev Neurosci 26:485–508
Scheiffele P, Fan J, Choih J, Fetter R, Serafini T (2000) Neuroligin expressed in nonneuronal cells triggers presynaptic development in contacting axons. Cell 101:657–669
Schultze W, Eulenburg V, Lessmann V, Herrmann L, Dittmar T, Gundelfinger ED, Heumann R, Erdmann KS (2001) Semaphorin4F interacts with the synapse-associated protein SAP90/PSD-95. J Neurochem 78:482–489
Schuster CM, Davis GW, Fetter RD, Goodman CS (1996) Genetic dissection of structural and functional components of synaptic plasticity. II. Fasciclin II controls presynaptic structural plasticity. Neuron 17:655–667
Seki T, Rutishauser U (1998) Removal of polysialic acid-neural cell adhesion molecule induces aberrant mossy fiber innervation and ectopic synaptogenesis in the hippocampus. J Neurosci 18:3757–3766
Senzaki K, Ogawa M, Yagi T (1999) Proteins of the CNR family are multiple receptors for reelin. Cell 99:635–647
Serafini T (1999) Finding a partner in a crowd: neuronal diversity and synaptogenesis. Cell 98:133–136
Shalizi A, Gaudilliere B, Yuan Z, Stegmuller J, Shirogane T, Ge Q, Tan Y, Schulman B, Harper JW, Bonni A (2006) A calcium-regulated MEF2 sumoylation switch controls postsynaptic differentiation. Science 311:1012–1017
Shan WS, Tanaka H, Phillips GR, Arndt K, Yoshida M, Colman DR, Shapiro L (2000) Functional cis-heterodimers of N- and R-cadherins. J Cell Biol 148:579–590
Shapiro L, Colman DR (1999) The diversity of cadherins and implications for a synaptic adhesive code in the CNS. Neuron 23:427–430
Shen K, Bargmann CI (2003) The immunoglobulin superfamily protein SYG-1 determines the location of specific synapses in C. elegans. Cell 112:619–630
Shen K, Fetter RD, Bargmann CI (2004) Synaptic specificity is generated by the synaptic guidepost protein SYG-2 and its receptor, SYG-1. Cell 116:869–881
Shimamura K, Takahashi T, Takeichi M (1992) E-cadherin expression in a particular subset of sensory neurons. Dev Biol 152:242–254
Shimoyama Y, Tsujimoto G, Kitajima M, Natori M (2000) Identification of three human type-II classic cadherins and frequent heterophilic interactions between different subclasses of type-II classic cadherins. Biochem J 349:159–167
Song JY, Ichtchenko K, Sudhof TC, Brose N (1999) Neuroligin 1 is a postsynaptic cell-adhesion molecule of excitatory synapses. Proc Natl Acad Sci USA 96:1100–1105
Sons MS, Busche N, Strenzke N, Moser T, Ernsberger U, Mooren FC, Zhang W, Ahmad M, Steffens H, Schomburg ED, Plomp JJ, Missler M (2006) Alpha-neurexins are required for efficient transmitter release and synaptic homeostasis at the mouse neuromuscular junction. Neuroscience 138:433–446
Sugita S, Khvochtev M, Sudhof TC (1999) Neurexins are functional alpha-latrotoxin receptors. Neuron 22:489–496
Sugita S, Saito F, Tang J, Satz J, Campbell K, Sudhof TC (2001) A stoichiometric complex of neurexins and dystroglycan in brain. J Cell Biol 154:435–445
Sunada Y, Bernier SM, Kozak CA, Yamada Y, Campbell KP (1994) Deficiency of merosin in dystrophic dy mice and genetic linkage of laminin M chain gene to dy locus. J Biol Chem 269:13729–13732
Suto F, Ito K, Uemura M, Shimizu M, Shinkawa Y, Sanbo M, Shinoda T, Tsuboi M, Takashima S, Yagi T, Fujisawa H (2005) Plexin-a4 mediates axon-repulsive activities of both secreted and transmembrane semaphorins and plays roles in nerve fiber guidance. J Neurosci 25:3628-3637
Suzuki K, Hu D, Bustos T, Zlotogora J, Richieri-Costa A, Helms JA, Spritz RA (2000) Mutations of PVRL1, encoding a cell-cell adhesion molecule/herpesvirus receptor, in cleft lip/palate-ectodermal dysplasia. Nat Genet 25:427–430
Suzuki SC, Inoue T, Kimura Y, Tanaka T, Takeichi M (1997) Neuronal circuits are subdivided by differential expression of type-II classic cadherins in postnatal mouse brains. Mol Cell Neurosci 9:433–447
Tabuchi K, Sudhof TC (2002) Structure and evolution of neurexin genes: insight into the mechanism of alternative splicing. Genomics 79:849–859
Takahashi K, Nakanishi H, Miyahara M, Mandai K, Satoh K, Satoh A, Nishioka H, Aoki J, Nomoto A, Mizoguchi A, Takai Y (1999) Nectin/PRR: an immunoglobulin-like cell adhesion molecule recruited to cadherin-based adherens junctions through interaction with afadin, a PDZ domain-containing protein. J Cell Biol 145:539–549
Takahashi T, Fournier A, Nakamura F, Wang LH, Murakami Y, Kalb RG, Fujisawa H, Strittmatter SM (1999) Plexin-neuropilin-1 complexes form functional semaphorin-3A receptors. Cell 99:59–69
Takeichi M (1995) Morphogenetic roles of classic cadherins. Curr Opin Cell Biol 7:619–627
Tamagnone L, Comoglio PM (2000) Signalling by semaphorin receptors: cell guidance and beyond. Trends Cell Biol 10:377–383
Tamagnone L, Comoglio PM (2004) To move or not to move? Semaphorin signalling in cell migration. EMBO Rep 5:356–361
Tanaka H, Shan W, Phillips GR, Arndt K, Bozdagi O, Shapiro L, Huntley GW, Benson DL, Colman DR (2000) Molecular modification of N-cadherin in response to synaptic activity. Neuron 25:93–107
Tang L, Hung CP, Schuman EM (1998) A role for the cadherin family of cell adhesion molecules in hippocampal long-term potentiation. Neuron 20:1165–1175
Taniguchi M, Yuasa S, Fujisawa H, Naruse I, Saga S, Mishina M, Yagi T (1997) Disruption of semaphorin III/D gene causes severe abnormality in peripheral nerve projection. Neuron 19:519–530
Taniguchi M, Nagao H, Takahashi YK, Yamaguchi M, Mitsui S, Yagi T, Mori K, Shimizu T (2003) Distorted odor maps in the olfactory bulb of semaphorin 3A-deficient mice. J Neurosci 23:1390–1397
Telo P, Breviario F, Huber P, Panzeri C, Dejana E (1998) Identification of a novel cadherin (vascular endothelial cadherin-2) located at intercellular junctions in endothelial cells. J Biol Chem 273:17565–17572
Tepass U, Truong K, Godt D, Ikura M, Peifer M (2000) Cadherins in embryonic and neural morphogenesis. Nat Rev Mol Cell Biol 1:91–100
Togashi H, Abe K, Mizoguchi A, Takaoka K, Chisaka O, Takeichi M (2002) Cadherin regulates dendritic spine morphogenesis. Neuron 35:77–89
Tomasiewicz H, Ono K, Yee D, Thompson C, Goridis C, Rutishauser U, Magnuson T (1993) Genetic deletion of a neural cell adhesion molecule variant (N-CAM-180) produces distinct defects in the central nervous system. Neuron 11:1163–1174
Uchida N, Honjo Y, Johnson KR, Wheelock MJ, Takeichi M (1996) The catenin/cadherin adhesion system is localized in synaptic junctions bordering transmitter release zones. J Cell Biol 135:767–779
Ullrich B, Ushkaryov YA, Sudhof TC (1995) Cartography of neurexins: more than 1000 isoforms generated by alternative splicing and expressed in distinct subsets of neurons. Neuron 14:497–507
Ulupinar E, Datwani A, Behar O, Fujisawa H, Erzurumlu R (1999) Role of semaphorin III in the developing rodent trigeminal system. Mol Cell Neurosci 13:281–292
Uryu K, Butler AK, Chesselet MF (1999) Synaptogenesis and ultrastructural localization of the polysialylated neural cell adhesion molecule in the developing striatum. J Comp Neurol 405:216–232
Ushkaryov YA, Petrenko AG, Geppert M, Sudhof TC (1992) Neurexins: synaptic cell surface proteins related to the alpha-latrotoxin receptor and laminin. Science 257:50–56
Van Vactor D, Wall DP, Johnson KG (2006) Heparan sulfate proteoglycans and the emergence of neuronal connectivity. Curr Opin Neurobiol 16:40–51
Vanhalst K, Kools P, Staes K, Roy F van, Redies C (2005) Delta-protocadherins: a gene family expressed differentially in the mouse brain. Cell Mol Life Sci 62:1247–1259
Varoqueaux F, Sigler A, Rhee JS, Brose N, Enk C, Reim K, Rosenmund C (2002) Total arrest of spontaneous and evoked synaptic transmission but normal synaptogenesis in the absence of Munc13-mediated vesicle priming. Proc Natl Acad Sci USA 99:9037–9042
Varoqueaux F, Jamain S, Brose N (2004) Neuroligin 2 is exclusively localized to inhibitory synapses. Eur J Cell Biol 83:449–456
Verhage M, Maia AS, Plomp JJ, Brussaard AB, Heeroma JH, Vermeer H, Toonen RF, Hammer RE, TK van den Berg, Missler M, Geuze HJ, Sudhof TC (2000) Synaptic assembly of the brain in the absence of neurotransmitter secretion. Science 287:864–869
Waites CL, Craig AM, Garner CC (2005) Mechanisms of vertebrate synaptogenesis. Annu Rev Neurosci 28:251–274
Wang CY, Chang K, Petralia RS, Wang YX, Seabold GK, Wenthold RJ (2006) A novel family of adhesion-like molecules that interacts with the NMDA receptor. J Neurosci 26:2174–2183
Wang X, Weiner JA, Levi S, Craig AM, Bradley A, Sanes JR (2002) Gamma protocadherins are required for survival of spinal interneurons. Neuron 36:843–854
Washbourne P, Dityatev A, Scheiffele P, Biederer T, Weiner JA, Christopherson KS, El-Husseini A (2004) Cell adhesion molecules in synapse formation. J Neurosci 24:9244–9249
Weiner JA, Wang X, Tapia JC, Sanes JR (2005) Gamma protocadherins are required for synaptic development in the spinal cord. Proc Natl Acad Sci USA 102:8–14
Weyden L van der, Adams DJ, Harris LW, Tannahill D, Arends MJ, Bradley A (2005) Null and conditional semaphorin 3B alleles using a flexible puroDeltatk loxP/FRT vector. Genesis 41:171–178
Weyden L van der, Arends MJ, Chausiaux OE, Ellis PJ, Lange UC, Surani MA, Affara N, Murakami Y, Adams DJ, Bradley A (2006) Loss of TSLC1 causes male infertility due to a defect at the spermatid stage of spermatogenesis. Mol Cell Biol 26:3595–3609
White FA, Behar O (2000) The development and subsequent elimination of aberrant peripheral axon projections in semaphorin3A null mutant mice. Dev Biol 225:79–86
Winberg ML, Mitchell KJ, Goodman CS (1998) Genetic analysis of the mechanisms controlling target selection: complementary and combinatorial functions of netrins, semaphorins, and IgCAMs. Cell 93:581–591
Wit J de, Verhaagen J (2003) Role of semaphorins in the adult nervous system. Prog Neurobiol 71:249–267
Withers GS, Higgins D, Charette M, Banker G (2000) Bone morphogenetic protein-7 enhances dendritic growth and receptivity to innervation in cultured hippocampal neurons. Eur J Neurosci 12:106–116
Wohrn JC, Puelles L, Nakagawa S, Takeichi M, Redies C (1998) Cadherin expression in the retina and retinofugal pathways of the chicken embryo. J Comp Neurol 396:20–38
Wolman MA, Liu Y, Tawarayama H, Shoji W, Halloran MC (2004) Repulsion and attraction of axons by semaphorin3D are mediated by different neuropilins in vivo. J Neurosci 24:8428–8435
Wong EV, Kenwrick S, Willems P, Lemmon V (1995) Mutations in the cell adhesion molecule L1 cause mental retardation. Trends Neurosci 18:168–172
Wong JT, Wong ST, O’Connor TP (1999) Ectopic semaphorin-1a functions as an attractive guidance cue for developing peripheral neurons. Nat Neurosci 2:798–803
Wu Q (2005) Comparative genomics and diversifying selection of the clustered vertebrate protocadherin genes. Genetics 169:2179–2188
Wu Q, Maniatis T (1999) A striking organization of a large family of human neural cadherin-like cell adhesion genes. Cell 97:779–790
Wu Q, Zhang T, Cheng JF, Kim Y, Grimwood J, Schmutz J, Dickson M, Noonan JP, Zhang MQ, Myers RM, Maniatis T (2001) Comparative DNA sequence analysis of mouse and human protocadherin gene clusters. Genome Res 11:389–404
Xu H, Wu XR, Wewer UM, Engvall E (1994) Murine muscular dystrophy caused by a mutation in the laminin alpha 2 (Lama2) gene. Nat Genet 8:297–302
Yagi T, Aizawa S, Tokunaga T, Shigetani Y, Takeda N, Ikawa Y (1993) A role for Fyn tyrosine kinase in the suckling behaviour of neonatal mice. Nature 366:742–745
Yamada S, Pokutta S, Drees F, Weis WI, Nelson WJ (2005) Deconstructing the cadherin-catenin-actin complex. Cell 123:889–901
Yamagata M, Herman JP, Sanes JR (1995) Lamina-specific expression of adhesion molecules in developing chick optic tectum. J Neurosci 15:4556–4571
Yamagata M, Weiner JA, Sanes JR (2002) Sidekicks: synaptic adhesion molecules that promote lamina-specific connectivity in the retina. Cell 110:649–660
Yamagata M, Sanes JR, Weiner JA (2003) Synaptic adhesion molecules. Curr Opin Cell Biol 15:621–632
Yu HH, Araj HH, Ralls SA, Kolodkin AL (1998) The transmembrane semaphorin sema I is required in Drosophila for embryonic motor and CNS axon guidance. Neuron 20:207–220
Yue Y, Chen ZY, Gale NW, Blair-Flynn J, Hu TJ, Yue X, Cooper M, Crockett DP, Yancopoulos GD, Tessarollo L, Zhou R (2002) Mistargeting hippocampal axons by expression of a truncated Eph receptor. Proc Natl Acad Sci USA 99:10777–10782
Zhai RG, Vardinon-Friedman H, Cases-Langhoff C, Becker B, Gundelfinger ED, Ziv NE, Garner CC (2001) Assembling the presynaptic active zone: a characterization of an active one precursor vesicle. Neuron 29:131–143
Zhang W, Rohlmann A, Sargsyan V, Aramuni G, Hammer RE, Sudhof TC, Missler M (2005) Extracellular domains of alpha-neurexins participate in regulating synaptic transmission by selectively affecting N- and P/Q-type Ca2+ channels. J Neurosci 25:4330–4342
Zhou YX, Zhao M, Li D, Shimazu K, Sakata K, Deng CX, Lu B (2003) Cerebellar deficits and hyperactivity in mice lacking Smad4. J Biol Chem 278:42313–42320
Ziv NE, Garner CC (2004) Cellular and molecular mechanisms of presynaptic assembly. Nat Rev Neurosci 5:385–399
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We thank Richard Fairless for helpful comments and Christian Bertram for help with artwork.
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Our studies are supported by the Deutsche Forschungsgemeinschaft (DFG-SFB 406, Germany). I.D. is a recipient of a Georg Christoph Lichtenberg Stipend (Ministry for Science and Culture of Lower Saxony, Germany).
An erratum to this article can be found at http://dx.doi.org/10.1007/s00441-006-0327-9
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Piechotta, K., Dudanova, I. & Missler, M. The resilient synapse: insights from genetic interference of synaptic cell adhesion molecules. Cell Tissue Res 326, 617–642 (2006). https://doi.org/10.1007/s00441-006-0267-4
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DOI: https://doi.org/10.1007/s00441-006-0267-4