Abstract
Neural cadherin (N-cadherin) is an adhesion receptor that is localized in abundance at neuron-to-neuron synapses. N-cadherin contains an extracellular domain that binds to other cadherins on juxtaposed cell membranes, a single-pass transmembrane region, and a cytoplasmic tail that interacts with various proteins, including catenins, kinases, phosphatases, and presenilin 1. N-cadherin contributes to the structural and functional organization of the synaptic complex by ensuring the adhesion between synaptic membranes and organizing the underlying actin cytoskeleton. Additionally, recent findings have shown that N-cadherin may participate in synaptic physiology by regulating calcium influx through voltage-activated calcium currents. The diverse activities of N-cadherin stem from its ability to operate as both an adhesion molecule that links cytoskeletons across cell membranes and a ligand-activated homophilic receptor capable of initiating intracellular signaling. An important mechanism of cadherin signaling is the regulation of small Rho guanosine triphosphatase activity that affects cytoskeleton dynamics and calcium influx. Because both the regulation of cadherin adhesive activity and cadherin-mediated signaling are affected by the binding of molecules to the intracellular domain, changes in the composition of the N-cadherin complex are central to the regulation of cadherin-mediated functions. This article focuses on the roles that N-cadherin might play at the level of the synapse through its effect on adhesion and signaling in the proximity of the synaptic junction.
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Hatta K., Okada T. S., and Takeichi M. (1985) A monoclonal antibody disrupting calcium-dependent cell-cell adhesion of brain tissues: possible role of its target antigen in animal pattern formation. Proc. Natl. Acad. Sci. USA 82(9), 2789–2793.
Takeichi M. (1991) Cadherin cell adhesion receptors as a morphogenetic regulator. Science 251(5000), 1451–1455.
Hatta K., Takagi S. Fujisawa H. and Takeichi M. (1987) Spatial and temporal expression pattern of N-cadherin cell adhesion molecules correlated with morphogenetic processes of chicken embryos. Dev. Biol. 120(1), 215–227.
Hatta K. and Takeichi M. (1986) Expression of N-cadherin adhesion molecules associated with early morphogenetic events in chick development. Nature 320(6061), 447–449.
Takeichi M. (1990) Cadherins: a molecular family important in selective cell-cell adhesion. Annu. Rev. Biochem. 59, 237–252.
Fannon A. M. and Colman D. R. (1996) A model for central synaptic junctional complex formation based on the differential adhesive specificities of the cadherins. Neuron 17(3), 423–434.
Uchida N., Honjo Y., Johnson K. R., Wheelock M. J., and Takeichi M. (1996) The catenin/cadherin adhesion system is localized in synaptic junctions bordering transmitter release zones. J. Cell Biol. 135(3), 767–779.
Nollet F., Kools, P., and van Roy F. (2000) Phylogenetic analysis of the cadherin superfamily allows identification of six major subfamilies besides several solitary members. J. Mol. Biol. 299(3), 551–572.
Redies C. (1995) Cadherin expression in the developing vertebrate CNS: from neuromeres to brain nuclei and neural circuits. Exp. Cell Res. 220(2), 243–256.
Suzuki S. C., Inoue T., Kumura Y., Tanaka T., and Takeichi M. (1997) Neuronal circuits are subdivided by differential expression of type-II classic cadherins in postnatal mouse brains. Mol. Cell Neurosci. 9(5/6), 433–447.
Price S. R., De Marco Garcia N. V., Ranscht B., and Jessell T. M. (2002) Regulation of motor neuron pool sorting by differential expression of type II cadherins. Cell 109(2), 205–216.
Lee C. H., Herman T., Clandinin T. R., Lee R., and Zipursky S. L. (2001) N-cadherin regulates target specificity in the Drosophila visual system. Neuron 30(2), 437–450.
Prakash S., Caldwell J. C., Eberl D. F., and Clandinin T. R. (2005) Drosophila N-cadherin mediates an attractive interaction between photoreceptor axons and their targets. Nat. Neurosci. 8(4), 443–450.
Shapiro L. and Colman D. R. (1999) The diversity of cadherins and implications for a synaptic adhesive code in the CNS. Neuron 23(3), 427–430.
Sano, K., Tanihara H. Heimark R. L. (1993) Protocadherins: a large family of cadherin-related molecules in central nervous system. EMBO J. 12(6) 2249–2256.
Wu Q. and Maniatis T. (1999) A striking organization of a large family of human neural cadherin-like cell adhesion genes. Cell 97(6), 779–790.
Wu Q. and Maniatis T. (2000) Large exons encoding multiple ectodomains are a characteristics feature of protocadherin genes. Proc. Natl. Acad. Sci. USA 97(7), 3124–3129.
Kohmura N., Senzaki K., Hamada S., et al. (1998) Diversity revealed by a novel family of cadherins expressed in neurons at a synaptic complex. Neuron 20(6), 1137–1151.
Wheelock M. J. and Johnson K. R. (2003) Cadherin-mediated cellular signaling. Curr. Opin. Cell Biol. 15(5), 509–514.
Yap A. S. and Kovasc E. M. (2003) Direct cadherin-activated cell signaling: a view from the plasma membrane. J. Cell Biol. 160(1), 11–16.
Gumbiner B. M. (2005) Regulation of cadherin-mediated adhesion in morphogenesis. Nat. Rev. Mol. Cell Biol. 6(8), 622–634.
Salinas P. C. and Price S. R. (2005) Cadherins and catenins in synapse development. Curr. Opin. Neurobiol. 15(1), 73–80.
Braga V. M. (2002) Cell-cell adhesion and signalling. Curr. Opin. Cell Biol. 14(5), 546–556.
Piccoli, G., Rutishauser U., and Brusés J. L. (2004) N-cadherin juxtamembrane domain modulates voltage-gated Ca2+ current via RhoA GTPase and Rho-associated kinase. J. Neurosci. 24(48), 10,918–10,923.
Marambaud P. Wen P. H., Dutt A., et al. (2003) A CBP binding transcriptional repressor produced by the PS1/epsilon-cleavage of N-cadherin is inhibited by PS1 FAD mutations. Cell 114(5), 635–645.
Nelson W. J. and Nusse R. (2004) Convergence of Wnt, beta-catenin, and cadherin pathways. Science 303(5663), 1483–1487.
Hatta K., Nose A., Nagafuchi A., and Takeichi M. (1988) Cloning and expression of cDNA encoding a neural calcium-dependent cell adhesion molecule: its identity in the cadherin gene family. J. Cell Biol. 106(3), 873–881.
Miyatani S., Shimamura K., Hatta M., et al. (1989) Neural cahderin: role in selective cell-cell adhesion. Science 245(4918), 631–635.
Shapiro L., Fannon A. M., Kwong, P. D., et al. (1995) Structural basis of cell-cell adhesion by cadherins. Nature 374(6520), 327–337.
Gumbiner B. M. (1993) Proteins associated with the cytoplasmic surface of adhesion molecules. Neuron 11(4), 551–564.
Yap A. S., Brieher W. M., and Gumbiner B. M. (1997) Molecular and functional analysis of cadherin-based adherens junctions. Annu. Rev. Cell Dev. Biol. 13, 119–146.
Kim J. B., Islam S., Kim Y. J., et al. (2000) N-Cadherin extracellular repeat 4 mediates epithelial to mesenchymal transition and increased motility. J. Cell Biol. 151(6), 1193–1206.
Koch A. W., Pokutta S., Lustig A., and Engel J. (1997) Calcium binding and homoassociation of E-cadherin domains. Biochemistry 36(25), 7697–7705.
Tamura K., Shan W. S., Hendrickson W. A., Colman D. R., and Shapiro L. (1998) Structure-function analysis of cell adhesion by neural (N-) cadherin. Neuron 20(6), 1153–1163.
Murase S. and Schuman E. M. (1999) The role of cell adhesion molecules in synaptic plasticity and memory. Curr. Opin. Cell Biol. 11(5), 549–553.
Kemler R. (1993) From cadherins to catenins: cytoplasmic protein interactions and regulation of cell adhesion. Trends Genet. 9(9), 317–321.
Daniel J. M. and Reynolds A. B. (1995) The tyrosine kinase substrate p120cas binds directly to E-cadherin but not to the adenomatous polyposis coli protein or alpha-catenin. Mol. Cell Biol. 15(9), 4819–4824.
Aberle H., Butz S., Stappert J., Weissig H., Kemler R., and Hoschuetzky H. (1994) Assembly of the cadherin-catenin complex in vitro with recombinant proteins. J. Cell Sci. 107(Pt 12), 3655–3663.
Hoschuetzky H., Aberle H., and Kemler R. (1994) Beta-catenin mediates the interaction of the cadherin-catenin complex with epidermal growth factor receptor. J. Cell Biol. 127(5), 1375–1380.
Pece S., Chiariello M., Murga C., and Gutkind J. S. (1999) Activation of the protein kinase Akt/PKB by the formation of E-cadherin-mediated cell-cell junctions. Evidence for the association of phosphatidylinositol 3-kinase with the E-cadherin adhesion complex. J. Biol. Chem. 274(27), 19,347–19,351.
Brady-Kalnay S. M., Rimm D. L., and Tonks N. K. (1995) Receptor protein tyrosine phosphatase PTPmu associates with cadherins and catenins in vivo. J. Cell Biol. 130(4), 977–986.
Steinberg M. S. and McNutt P. M. (1999) Cadherins and their connections: adhesion junctions have broader functions. Curr. Opin. Cell Biol. 11(5), 554–560.
Meigs T. E., Fields T. A., McKee D. D., and Casey P. J. (2001) Interaction of Galpha 12 and Galpha 13 with the cytoplasmic domain of cadherin provides a mechanism for beta—catenin release. Proc. Natl. Acad. Sci. USA 98(2), 519–524.
Fujita Y., Krause G., Scheffner M., et al. (2002) Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex. Nat. Cell Biol. 4(3), 222–231.
Xu Y., Guo D. F., Davidson M., Inagami T., and Carpenter G. (1997) Interaction of the adaptor protein Shc and the adhesion molecule cadherin. J. Biol. Chem. 272(21) 13463–13466.
Baki L., Marambaud P., Efthimiopoulos S., et al. (2001) Presenilin-1 binds cytoplasmic epithelial cadherin, inhibits cadherin/p120 association, and regulates stability and function of the cadherin/catenin adhesion complex. Proc. Natl. Acad. Sci. USA 98(5) 2381–2386.
Nagafuchi A. and Takeichi M. (1988) Cell binding function of E-cadherin is regulated by the cytoplasmic domain. EMBO J. 7(12) 3679–3684.
Knudsen K. A., Soler A. P., Johnson K. R., and Wheelock M. J. (1995) Interaction of alphaactinin with the cadherin/catenin cell-cell adhesion complex via alpha-catenin. J. Cell. Biol. 130(1), 67–77.
Anastasiadis P. Z. and Reynolds A. B. (2000) The p120 catenin family: complex roles in adhesion, signaling and cancer. J. Cell Sci. 113(Pt 8), 1319–1334.
Yap A. S., Niessen C. M., and Gumbiner B. M. (1998) The juxtamembrane region of the cadherin cytoplasmic tail supports lateral clustering, adhesive strengthening, and interaction with p120ctn. J. Cell Biol. 141 (3), 779–789.
Yap A. S., Brieher W. M., Pruschy M., and Gumbiner B. M. (1997) Lateral clustering of the adhesive ectodomain: a fundamental determinant of cadherin function. Curr. Biol. 7(5), 308–315.
Gumbiner B. M. (2000) Regulation of cadherin adhesive activity. J. Cell Biol. 148(3), 399–404.
Anastasiadis P. Z., Moon S. Y., Thoreson M. A., et al. (2000) Inhibition of RhoA by p120 catenin. Nat. Cell Biol. 2(9), 637–644.
Noren N. K., Liu B. P., Burridge K., and Kreft B. (2000) p120 catenin regulates the actin cytoskeleton via Rho family GTPases. J. Cell Biol. 150(3), 567–580.
Gottardi C. J. and Gumbiner B. M. (2001) Adhesion signaling: how beta-catenin interacts with its partners. Curr Biol. 11(19), R792-R794.
Anastasiadis P. Z. and Reynolds A. B. (2001) Regulation of Rho GTPases by p120-catenin. Curr. Opin. Cell Biol. 13(5), 604–610.
Heasman J., Crawford A., Goldstone K., et al. (1994) Overexpression of cadherins and under-expression of beta-catenin inhibit dorsal mesoderm induction in early Xenopus embryos. Cell 79(5), 791–803.
Fagotto F., Funayama N., Gluck U., and Gumbiner B. M. (1996) Binding to cadherins antagonizes the signaling activity of beta-catenin during axis formation in Xenopus. J. Cell Biol. 132(6), 1105–1114.
Gottardi C. J., Wong E., and Gumbiner B. M. (2001) E-cadherin suppresses cellular transformation by inhibiting beta-catenin signaling in an adhesion-independent manner. J. Cell Biol. 153(5), 1049–1060.
Chen H., Paradies N. E., Fedor-Chaiken M., and Brackenbury R. (1997) E-cadherin mediates adhesion and suppresses cell motility via distinct mechanisms. J. Cell Sci. 110 (Pt 3), 345–356.
Horikawa K. and Takeichi M. (2001) Requirement of the juxtamembrane domain of the cadherin cytoplasmic tail for morphogenetic cell rearrangement during myotome development. J. Cell Biol. 155(7) 1297–1306.
Riehl R., Johnson K., Bradley R., et al. (1996) Cadherin function is required for axon outgrowth in retinal ganglion cells in vivo. Neuron 17(5), 837–848.
Fukata M. and Kaibuchi K. (2001) Rho-family GTPases in cadherin-mediated cell-cell adhesion. Nat. Rev. Mol. Cell Biol. 2(12), 887–897.
Takaishi K., Sasaki T., Kotani H., Nishioka H., and Takai Y. (1997) Regulation of cell-cell adhesion by rac and rho small G proteins in MDCK cells. J. Cell Biol. 139(4), 1047–1059.
Braga V. M., Del Maschio A., Machesky L., and Dejana E. (1999) Regulation of cadherin function by Rho and Rac: modulation by junction maturation and cellular context Mol. Biol. Cell. 10(1), 9–22.
Jou T. S. and Nelson W. J. (1998) Effects of regulated expression of mutant RhoA and Rac1 small GTPases on the development of epithelial (MDCK) cell polarity. J. Cell Biol. 142(1), 85–100.
Jou T. S., Schneeberger E. E., and Nelson W. J. (1998) Structural and functional regulation of tight junctions by RhoA and Rac1 small GTPases. J. Cell Biol. 142(1), 101–115.
Braga V. (2000) Epithelial cell shape: cadherins and small GTPases. Exp. Cell Res. 261 (1), 83–90.
Ehrlich J. S., Hansen M. D., and Nelson W. J. (2002) Spatio-temporal regulation of Rac1 localization and lamellipodia dynamics during epithelial cell-cell adhesion. Dev. Cell. 3(2), 259–270.
Noren N. K., Arthur W. T., and Burridge K. (2003) Cadherin engagement inhibits RhoA via p190RhoGAP. J. Biol. Chem. 278(16), 13,615–13,618.
Noren N. K., Niessen C. M., Gumbiner B. M., and Burridge K. (2001). Cadherin engagement regulates Rho family GTPases. J. Biol. Chem. 276(36), 33,305–33,308.
Kovacs E. M., Ali P. G., McCormack A. J., and Yap A. S. (2002) E-cadherin homophilic ligation directly signals through Rac and phosphatidylinositol 3-kinase to regulate adhesive contacts. J. Biol. Chem. 277(8), 6708–6718.
Charrasse S., Meriane M., Comunale F., Blangy A., and Gauthier-Rouviere C. (2002) N-cadherin-dependent cell-cell contact regulates Rho GTPases and beta-catenin localization in mouse C2C12 myoblasts. J. Cell Biol. 158(5), 953–965.
Kim S. H., Li Z., and Sacks D. B. (2000) E-cadherin-mediated cell-cell attachment activates Cdc42. J. Biol. Chem. 275(47), 36,999–37,005.
Sander E. E., van Delft S., ten Klooster J. P., et al. (1998) Matrix-dependent Tiam1/Rac signaling in epithelial cells promotes either cell-cell adhesion or cell migration and is regulated by phosphatidylinositol 3-kinase. J. Cell Biol. 143(5), 1385–1398.
Rottner K., Hall A., and Small J. V. (1999) Interplay between Rac and Rho in the control of substrate contact dynamics. Curr. Biol. 9(12), 640–648.
Li Z., Aizenman C. D., and Cline H. T. (2002) Regulation of rho GTPases by crosstalk and neuronal activity in vivo. Neuron 33(5), 741–750.
Hawkins P. T., Eguinoa A., Qiu R. G., et al. (1995) PDGF stimulates an increase in GTP-Rac via activation of phosphoinositide 3-kinase. Curr. Biol. 5(4), 393–403.
Sander E. E., ten Klooster J. P., van Delft S., van der Kammen R. A., and Collard J. G. (1999) Rac downregulates Rho activity: reciprocal balance between both GTPases determines cellular morphology and migratory behavior J. Cell Biol. 147(5), 1009–1022.
Lampugnani M. G., Zanetti A., Breviario F., et al. (2002) VE-cadherin regulates endothelial actin activating Rac and increasing membrane association of Tian. Mol. Biol. Cell. 13(4), 1175–1189.
Schuebel K. E., Movilla N., Rosa J. L., and Bustelo X. R. (1998) Phosphorylation-dependent and constitutive activation of Rho proteins by wild-type and oncogenic Vav-2. EMBO J. 17(22), 6608–6621.
Abe K., Rossman K. L., Liu B., et al. (2000) Vav2 is an activator of Cdc42, Rac1, and RhoA. J. Biol. Chem. 275(14), 10,141–10,149.
Tricaud N., Perrin-Tricaud C., Brusés J. L., and Rutishauser U. (2005) Adherens junctions in myelinating Schwann cells stabilize Schmidt-Lanterman incisures via recruitment of p120 catenin to E-cadherin. J. Neurosci. 25(13), 3259–3269.
Kovacs E. M., Goodwin M., Ali R. G., Paterson A. D., and Yap A. S. (2002) Cadherin-directed actin assembly: E-cadherin physically associates with the Arp2/3 complex to direct actin assembly in nascent adhesive contacts. Curr. Biol. 12(5), 379–382.
Kovacs E. M. and Yap A. S. (2002) The web and the rock: cell adhesion and the ARP2/3 complex. Dev. Cell. 3(6), 760–761.
Fukata M., Kuroda S., Nakagawa M., et al. (1999) Cdc42 and Rac1 regulate the interaction of IOGAP1 with beta-catenin. J. Biol. Chem. 274(37), 26,044–26,050.
Kuroda S., Fukata M., Nakagawa M., et al. (1998) Role of IQGAP1, a target of the small GTPases Cdc42 and Rac1, in regulation of E-cadherin-mediated cell-cell adhesion. Science 281(5378), 832–835.
Li Z., Kim S. H., Higgins J. M., Brenner M. B., and Sacks D. B. (1999) IQGAP1 and calmodulin modulate E-cadherin function. J. Biol. Chem. 274(53), 37,885–37,892.
Magie C. R., Pinto-Santini D., and Parkhurst S. M. (2002) Rho1 interacts with p120ctn and alpha-catenin, and regulates cadherin-based adherens junction components in Drosophila. Development 129(16), 3771–3782.
Braga V. M., Hajibagheri N., and Watt F. M. (1998) Calcium-induced intercellular adhesion of keratinocytes does not involve accumulation of beta 1 integrins at cell-cell contacts and does not involve changes in the levels or phosphorylation of catenins. Cell Adhes. Commun. 5(2), 137–149.
Brieher W. M. and Gumbiner B. M. (1994) Regulation of C-cadherin function during activin induced morphogenesis of Xenopus animal caps. J. Cell Biol. 126(2), 519–527.
Shibamoto S., Hayakawa M., Takeuchi K., et al. (1994) Tyrosine phosphorylation of beta-catenin and plakoglobin enhanced by hepatocyte growth factor and epidermal growth factor in human carcinoma cells. Cell Adhes. Commun. 1(4), 295–305.
Weidner K. M., Behrens J., Vandekerckhove J., and Birchmeier W. (1990) Scatter factor: molecular characteristics and effect on the invasiveness of epithelial cells. J. Cell Biol. 111(5 Pt 1), 2097–2108.
Rubio M. E., Curcio C., Chauvet N., and Brusés J. L. (2005) Assembly of the N-cadherin complex during synapse formation involves uncoupling of p120-catenin and association with presenilin 1. Mol. Cell Neurosci. 30(4), 611–623.
Chauvet N., Prieto M., Fabre C., Noren N. K., and Privat A. (2003) Distribution of p120 catenin during rat brain development: potential role in regulation of cadherin-mediated adhesion and actin cytoskeleton organization. Mol. Cell Neurosci. 22(4), 467–486.
Huntley G. W. and Benson D. L. (1999) Neural (N)-cadherin at developing thalamocortical synapses provides an adhesion mechanism for the formation of somatopically organized connections. J. Comp. Neurol. 407(4), 453–471.
Phillips G. R., Huang J. K., Wang Y., et al. (2001) The presynaptic particle web: ultrastructure, composition, dissolution, and reconstitution. Neuron 32(1), 63–77.
Beesley P. W., Mummery R., and Tibaldi J. (1995) N-cadherin is a major glycoprotein component of isolated rat forebrain postsynaptic densities. J. Neurochem. 64(5), 2288–2294.
Yamagata M., Herman J. P., and Sanes J. R. (1995) Lamina-specific expression of adhesion molecules in developing chick optic tectum. J. Neurosci. 15(6), 4556–4571.
Squitti R., De Stefano M. E., Edgar D., and Toschi G. (1999) Effects of axotomy on the expression and ultrastructural localization of N-cadherin and neural cell adhesion molecule in the quail ciliary ganglion: an in vivo model of neuroplasticity. Neuroscience 91(2), 707–722.
Benson D. L. and Tanaka H. (1998) N-cadherin redistribution during synaptogenesis in hippocampal neurons. J. Neurosci. 18(17), 6892–6904.
Bozdagi O., Shan W., Tanaka H., Benson D. L., and Huntley G. W. (2000) Increasing numbers of synaptic puncta during late-phase LTP: N-cadherin is synthesized, recruited to synaptic sites, and required for potentiation, Neuron 28(1), 245–259.
Buchanan J., Sun Y. A., and Poo M. M. (1989) Studies of nerve-muscle interactions in Xenopus cell culture: fine structure of early functional contacts, J. Neurosci. 9(5), 1540–1554.
Evers J., Laser M., Sun Y. A., Xie Z. P., and Poo M. M. (1989) Studies of nerve-muscle interactions in Xenopus cell culture: analysis of early synaptic currents. J. Neurosci. 9(5), 1523–1539.
Pilar G., Tuttle J., and Vaca K. (1981) Functional maturation of motor nerve terminals in the avian iris: ultrastructure, transmitter metabolism and synaptic reliability. J. Physiol. (Lond.) 321, 175–193.
Gumbiner B., Stevenson B., and Grimaldi A. (1988) The role of the cell adhesion molecule uvomorulin in the formation and maintenance of the epithelial junctional complex. J. Cell Biol. 107(4), 1575–1587.
Meyer R. A., Laird D. W., Revel J. P., and Johnson R. G. (1992) Inhibition of gap junction and adherens junction assembly by connexin and A-CAM antibodies. J. Cell. Biol. 119(1), 179–189.
Watabe M., Nagafuchi A., Tsukita S., and Takeichi M. (1994) Induction of polarized cell-cell association and retardation of growth by activation of the E-cadherin-catenin adhesion system in a dispersed carcinoma line. J. Cell Biol. 127(1), 247–256.
Brusés J. L. (2000) Cadherin-mediated adhesion at the interneuronal synapse. Curr. Opin. Cell Biol. 12(5), 593–597.
Peters, A., Palay, S. L., and Webster, H. D. (1991) The fine structure of the nervous system, New York: Oxford University Press.
Vaughn J. E. (1989) Fine structure of synaptogenesis in the vertebrate central nervous system. Synapse. 3(3), 255–285.
Tanaka H., Shan W., Phillips G. R., et al. (2000) Molecular modification of N-cadherin in response to synaptic activity. Neuron 25(1), 93–107.
Aono S., Nakagawa S., Reynolds A. B., and Takeichi M. (1999) p120(ctn) acts as an inhibitory regulator of cadherin function in colon carcinoma cells. J. Cell Biol. 145(3), 551–562.
Ohkubo T. and Ozawa M. (1999) p120ctn binds to the membrane-proximal region of the E-cadherin cytoplasmic domain and is involved in modulation of adhesion activity. J. Cell Biol. 274, 21,409–21,415.
Yu G., Chen G., Levesque G., et al. (1998) The presenilin 1 protein is a component of a high molecular weight intracellular complex that contains beta-catenin. J. Biol. Chem. 273(26), 16,470–16,475
Zhang W. and Benson D. L. (2001) Stages of synapse development defined by dependence on F-actin. J. Neurosci. 21(14), 5169–5181.
Vasioukhin V., Bauer C., Yin M., and Fuchs E. (2000) Directed actin polymerization is the driving force for epithelial cell-cell adhesion. Cell 100(2), 209–219.
Hall A. (1998) Rho GTPases and the actin cytoskeleton. Science 279(5350), 509–514.
Amano M., Ito M., Kimura, K., et al. (1996) Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase). J. Biol. Chem. 271(34), 20,246–20,249.
Sahai E. and Marshall C. J. (2002) ROCK and Dia have opposing effects on adherens junctions downstream of Rho. Nat. Cell Biol. 4(6), 408–415.
Rueckschloss U. and Isenberg G. (2001) Cytochalasin D reduces Ca2+ currents via cofilin-activated depolymerization of F-actin in guinea-pig cardiomyocytes. J. Physiol. 537(Pt 2), 363–370.
Ward Y., Yap S. F., Ravichandran V., et al. (2002) The GTP binding proteins Gem and Rad are negative regulators of the Rho-Rho kinase pathway. J. Cell Biol. 157(2), 291–302.
Wilk-Blaszczak M. A., Singer W. D., Quill T., et al. (1997) The monomeric G-proteins Racl and/or Cdc42 are required for the inhibition of voltage-dependent calcium current by bradykinin. J. Neurosci. 17(11), 4094–4100.
White M. G., Crumling M. A., and Meriney S. D. (1997) Developmental changes in calcium current pharmacology and somatostatin inhibition in chick parasympathetic neurons. J. Neurosci. 17(16), 6302–6313.
Scheiffele P., Fan J., Choih J., Fetter, R., and Serafini T. (2000) Neuroligin expressed in nonneuronal cells triggers presynaptic development in contacting axons. Cell 101(6), 657–669.
Bamji S. X., Shimazu K., Kimes N., et al. (2003) Role of beta-catenin in synaptic vesicle localization and presynaptic assembly. Neuron 40(4), 719–731.
Togashi H., Abe K., Mizoguchi A., Takaoka K., Chisaka O., and Takeichi M. (2002) Gadherin regulates dendritic spine morphogenesis. Neuron 35(1), 77–89.
Bozdagi O., Valcin M., Poskanzer K., Tanaka H., and Benson D. L. (2004) Temporally distinct demands for classic cadherins in synapse formation and maturation. Mol. Cell Neurosci. 27(4), 509–521.
Erdmann B., Kisch F. P., Ratnjen F. G., More, M. I. (2003) N-cadherin is essential for retinal lamination in the zebrafish. Dev. Dyn. 226(3), 570–577.
Perego C, Vanoni C., Massari S., Longhi R., and Pietrini G. (2000) Mammalian LIN-7 PDZ proteins associate with beta-catenin at the cell-cell junctions of epithelia and neurons. EMBO J. 19(15), 3978–3989.
Abe K., Chisaka O., Van Roy F., and Takeichi M. (2004) Stability of dendritic spines and synaptic contacts is controlled by alpha N-catenin. Nat. Neurosci. 7(4), 357–363.
Okamura K., Tanaka H., Yagita Y., et al. (2004) Cadherin activity is required for activity-induced spine remodeling. J. Cell Biol. 167(5), 961–972.
Zhai R. G., Vardinon-Friedman H., Cases-Lang-hoff, C., et al. (2001) Assembling the presynaptic active zone: a characterization of an active one precursor vesicle. Neuron 29(1), 131–143.
Iwai Y., Hirota Y., Ozaki K., Okano H., Takeichi M., and Uemura T. (2002) DN-cadherin is required for spatial arrangement of nerve terminals and ultrastructural organization of synapses. Mol. Cell Neurosci. 19(3), 375–388.
Tang L., Hung C. P., and Schuman E. M. (1998) A role for the cadherin family of cell adhesion molecules in hippocampal long-term potentiation. Neuron 20(6), 1165–1175.
Vassilev P. M., Mitchel J., Vassilev M., Kanazirska, M., and Brown E. M. (1997) Assessment of frequency-dependent alterations in the level of extracellular Ca2+ in the synaptic cleft. Biophys. J. 72(5), 2103–2116.
Nicholson C, ten Bruggencate G., Stockle H., and Steinberg R. (1978) Calcium and potassium changes in extracellular microenvironment of cat cerebellar cortex. J. Neurophysiol. 41(4), 1026–1039.
Krnjevic K., Morris M. E., and Reiffenstein R. J. (1982) Stimulation-evoked changes in extracellular K+ and Ca2+ in pyramidal layers of the rat's hippocampus, Can. J. Physiol. Pharmacol. 60(12), 1643–1657.
Borst J. G. and Sakmann B. (1999) Depletion of calcium in the synaptic cleft of a calyx-type synapse in the rat brainstem. J. Physiol. 521(Pt 1), 123–133.
Spafford J. D. and Zamponi G. W. (2003) Functional interactions between presynaptic calcium channels and the neurotransmitter release machinery. Curr. Opin. Neurobiol. 13(3), 308–314.
Bixby J. L., Grunwald G. B., and Bookman R. J. (1994) Ca2+ influx and neurite growth in response to purified N-cadherin and laminin. J. Cell Biol. 127(5), 1461–1475.
Steinberg M. S. and Takeichi M. (1994) Experimental specification of cell sorting, tissue spreading, and specific spatial patterning by quantitative differences in cadherin expression. Proc. Natl. Acad. Sci. USA 91(1), 206–209.
Nose A., Nagafuchi A., and Takeichi M. (1988) Expressed recombinant cadherins mediate cell sorting in model systems. Cell 54(7), 993–1001.
Brieher W. M., Yap A. S., and Gumbiner B. M. (1996) Lateral dimerization is required for the homophilic binding activity of C-cadherin. J. Cell Biol. 135(2), 487–496.
Tomschy A., Fauser C., Landwehr R., and Engel J. (1996) Homophilic adhesion of E-cadherin occurs by a co-operative two-step interaction of N-terminal domains. EMBO J. 15(14), 3507–3514.
Sheng M., McFadden G., and Greenberg M. E. (1990). Membrane depolarization and calcium induced c-fos transcription via phosphorylation of transcription factor CREB. Neuron 4(4), 571–582.
Morishita W., Connor J. H., Xia H., Quinlan E. M.. Shenolikar S., and Malenka R. C. (2001) Regulation of synaptic strength by protein phosphatase 1. Neuron 32(6), 1133–1148.
Vaillant A. R., Mazzoni I., Tudan C., Boudreau M., Kaplan D. R., and Miller F. D. (1999) Depolarization and neurotrophins converge on the phosphatidylinositol 3-kinase-Akt pathway to synergistically regulate neuronal survival. J. Cell Biol. 146(5), 955–966.
Lisman J., Schulman H., and Cline H. (2002) The molecular basis of CaMKII function in synaptic and behavioural memory. Nat. Rev. Neurosci. 3(3), 175–190.
Daniel J. M. and Reynolds A. B. (1997) Tyrosine phosphorylation and cadherin/catenin function. Bioessays 19(10), 883–891.
Matsuyoshi N., Hamaguchi M., Taniguchi S., Nagafuchi A., Tsukita S., and Takeichi M. (1992) Cadherin-mediated cell-cell adhesion is perturbed by v-src tyrosine phosphorylation in metastatic fibroblasts. J. Cell Biol. 118(3), 703–714.
Behrens J., Vakaet L., Friis R., et al. (1993) Loss of epithelial differentiation and gain of invasiveness correlates with tyrosine phosphorylation of the E-cadherin/beta-catenin complex in cells transformed with a temperature-sensitive v-SRC gene. J. Cell Biol. 120(3), 757–766.
Gottardi C. J. and Gumbiner B. M. (2004) Distinct molecular forms of beta-catenin are targeted to adhesive or transcriptional complexes. J. Cell Biol. 167(2), 339–349.
Bixby J. L. and Zhang R. (1990) Purified N-cadherin is a potent substrate for the rapid induction of neurite outgrowth. J. Cell Biol. 110(4), 1253–1260.
Lo Y. J. and Poo M. M. (1991) Activity-dependent synaptic competition in vitro: heterosynaptic suppression of developing synapses. Science 254(5034), 1019–1022.
Wan J. and Poo M. (1999) Activity-induced potentiation of developing neuromuscular synapses. Science 285(5434), 1725–1728.
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Brusés, J.L. N-Cadherin signaling in synapse formation and neuronal physiology. Mol Neurobiol 33, 237–252 (2006). https://doi.org/10.1385/MN:33:3:237
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DOI: https://doi.org/10.1385/MN:33:3:237