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Neural recognition molecules of the immunoglobulin superfamily: signaling transducers of axon guidance and neuronal migration

A Corrigendum to this article was published on 01 February 2007

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Abstract

Recognition molecules of the immunoglobulin superfamily have important roles in neuronal interactions during ontogeny, including migration, survival, axon guidance and synaptic targeting. Their downstream signal transduction events specify whether a cell changes its place of residence or projects axons and dendrites to targets in the brain, allowing the construction of a dynamic neural network. A wealth of recent discoveries shows that cell adhesion molecules interact with attractant and repellent guidance receptors to control growth cone and cell motility in a coordinate fashion. We focus on the best-studied subclasses, the neural cell adhesion molecule NCAM and the L1 family of adhesion molecules, which share important structural and functional features. We have chosen these paradigmatic molecules and their interactions with other recognition molecules as instructive for elucidating the mechanisms by which other recognition molecules may guide cell interactions during development or modify their function as a result of injury, learning and memory.

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Figure 1: Signal transduction pathways activated by 140- and 180-kD NCAM isoforms outside (left) and inside (right) lipid raft compartments of the plasma membrane are presented as a composite map, component parts of which may occur in cell type– or physiological context–specific situations.

Kimberly Caesar

Figure 2: Signaling pathways downstream of L1 and CHL1.

Kimberly Caesar

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References

  1. Stork, O., Welzl, H., Cremer, H. & Schachner, M. Increased intermale aggression and neuroendocrine response in mice deficient for the neural cell adhesion molecules. Eur. J. Neurosci. 9, 1117–1125 (1997).

    CAS  PubMed  Google Scholar 

  2. Stork, O. et al. Anxiety and increased 5-HT1A receptor response in NCAM null mutant mice. J. Neurobiol. 40, 343–355 (1999).

    CAS  PubMed  Google Scholar 

  3. Kenwrick, S., Watkins, A. & Angelis, E.D. Neural cell recognition molecule L1: relating biological complexity to human disease mutations. Hum. Mol. Genet. 9, 879–886 (2000).

    CAS  PubMed  Google Scholar 

  4. Frints, S.G.M. et al. CALL interrupted in a patient with nonspecific mental retardation: gene dosage-dependent alteration of murine brain development and behavior. Hum. Mol. Genet. 12, 1463–1474 (2003).

    CAS  PubMed  Google Scholar 

  5. Kurumaji, A., Nomoto, H., Okano, T. & Toru, M. An association study between polymorphism of L1CAM gene and schizophrenia in a Japanese sample. Am. J. Med. Genet. 105, 99–104 (2001).

    CAS  PubMed  Google Scholar 

  6. Sakurai, K., Migita, O., Toru, M. & Arinami, T. An association between a missense polymorphism in the close homologue of L1 (CHL1, CALL) gene and schizophrenia. Mol. Psychiatry 7, 412–415 (2002).

    CAS  PubMed  Google Scholar 

  7. Kleene, R. & Schachner, M. Glycans and neural cell interactions. Nat. Rev. Neurosci. 5, 195–208 (2004).

    CAS  PubMed  Google Scholar 

  8. Weinhold, B. et al. Genetic ablation of polysialic acid causes severe neurodevelopmental defects rescued by deletion of the neural cell adhesion molecule. J. Biol. Chem. 280, 42971–42977 (2005).

    CAS  PubMed  Google Scholar 

  9. Angata, K. et al. Sialyltransferase ST8Sia-II assembles a subset of polysialic acid that directs hippocampal axonal targeting and promotes fear behavior. J. Biol. Chem. 279, 32603–32613 (2004).

    CAS  PubMed  Google Scholar 

  10. Eckhardt, M. et al. Mice deficient in the polysialyltransferase ST8SiaIV/PST-1 allow discrimination of the roles of neural cell adhesion molecule protein and polysialic acid in neural development and synaptic plasticity. J. Neurosci. 20, 5234–5244 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Petridis, A.K., El-Maarouf, A. & Rutishauser, U. Polysialic acid regulates cell contact-dependent neuronal differentiation of progenitor cells from the subventricular zone. Dev. Dyn. 230, 675–684 (2004).

    CAS  PubMed  Google Scholar 

  12. Johnson, C.P., Fujimoto, I., Rutishauser, U. & Leckband, D.E. Direct evidence that NCAM polysialylation increases intermembrane repulsion and abrogates adhesion. J. Biol. Chem. 280, 137–145 (2005).

    CAS  PubMed  Google Scholar 

  13. Persohn, E., Pollerberg, G.E. & Schachner, M. 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 (1989).

    CAS  PubMed  Google Scholar 

  14. Polo-Parada, L., Bose, C.M. & Landmesser, L.T. Alterations in transmission, vesicle dynamics, and transmitter release machinery at NCAM-deficient neuromuscular junctions. Neuron 32, 815–828 (2001).

    CAS  PubMed  Google Scholar 

  15. Polo-Parada, L., Bose, C.M., Plattner, F. & Landmesser, L.T. 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 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Polo-Parada, L., Plattner, F., Bose, C. & Landmesser, L.T. NCAM 180 acting via a conserved C-terminal domain and MLCK is essential for effective transmission with repetitive stimulation. Neuron 46, 917–931 (2005).

    CAS  PubMed  Google Scholar 

  17. Muhlenhoff, M., Eckhardt, M., Bethe, A., Frosch, M. & Gerardy-Schahn, R. Autocatalytic polysialylation of polysialyltransferase-1. EMBO J. 15, 6943–6950 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Mendiratta, S.S., Sekulic, N., Lavie, A. & Colley, K.J. Specific amino acids in the first fibronectin type III repeat of the neural cell adhesion molecule play a role in its recognition and polysialylation by the polysialyltransferase ST8Sia IV/PST. J. Biol. Chem. 280, 32340–32348 (2005).

    CAS  PubMed  Google Scholar 

  19. Kiselyov, V.V., Soroka, V., Berezin, V. & Bock, E. Structural biology of NCAM homophilic binding and activation of FGFR. J. Neurochem. 94, 1169–1179 (2005).

    CAS  PubMed  Google Scholar 

  20. Anderson, A.A. et al. A peptide from the first fibronectin domain of NCAM acts as an inverse agonist and stimulates FGF receptor activation, neurite outgrowth and survival. J. Neurochem. 95, 570–583 (2005).

    CAS  PubMed  Google Scholar 

  21. Johnson, C.P., Fujimoto, I., Perrin-Tricaud, C., Rutishauser, U. & Leckband, D. Mechanism of homophilic adhesion by the neural cell adhesion molecule: use of multiple domains and flexibility. Proc. Natl. Acad. Sci. USA 101, 6963–6968 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Doherty, P., Williams, G. & Williams, E.J. CAMs and axonal growth: a critical evaluation of the role of calcium and the MAPK cascade. Mol. Cell. Neurosci. 16, 283–295 (2000).

    CAS  PubMed  Google Scholar 

  23. Rao, Y., Zhao, X. & Siu, C.H. Mechanism of homophilic binding mediated by the neural cell adhesion molecule NCAM. Evidence for isologous interaction. J. Biol. Chem. 269, 27540–27548 (1994).

    CAS  PubMed  Google Scholar 

  24. Bennett, V. & Baines, A.J. Spectrin and ankyrin-based pathways: metazoan inventions for integrating cells into tissues. Physiol. Rev. 81, 1353–1392 (2001).

    CAS  PubMed  Google Scholar 

  25. Dahlin-Huppe, K., Berglund, E.O., Ranscht, B. & Stallcup, W.B. Mutational analysis of the L1 neuronal cell adhesion molecule identifies membrane-proximal amino acids of the cytoplasmic domain that are required for cytoskeletal anchorage. Mol. Cell. Neurosci. 9, 144–156 (1997).

    CAS  PubMed  Google Scholar 

  26. Dickson, T.C., Mintz, C.D., Benson, D.L. & Salton, S.R. Functional binding interaction identified between the axonal CAM L1 and members of the ERM family. J. Cell Biol. 157, 1105–1112 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Kamiguchi, H. et al. The neural cell adhesion molecule L1 interacts with the AP-2 adaptor and is endocytosed via the clathrin-mediated pathway. J. Neurosci. 18, 5311–5321 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Jacob, J., Haspel, J., Kane-Goldsmith, N. & Grumet, M. L1 mediated homophilic binding and neurite outgrowth are modulated by alternative splicing of exon 2. J. Neurobiol. 51, 177–189 (2002).

    CAS  PubMed  Google Scholar 

  29. Castellani, V., De Angelis, E., Kenwrick, S. & Rougon, G. Cis and trans interactions of L1 with neuropilin-1 control axonal responses to semaphorin 3A. EMBO J. 21, 6348–6357 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Julien, F. et al. Dual functional activity of semaphorin 3B is required for positioning the anterior commissure. Neuron 48, 63–75 (2005).

    CAS  PubMed  Google Scholar 

  31. Schuch, U., Lohse, M.J. & Schachner, M. Neural cell adhesion molecules influence second messenger systems. Neuron 3, 13–20 (1989).

    CAS  PubMed  Google Scholar 

  32. Beggs, H.E., Soriano, P. & Maness, P.F. NCAM-dependent neurite outgrowth is inhibited in neurons from fyn-minus mice. J. Cell Biol. 127, 825–833 (1994).

    CAS  PubMed  Google Scholar 

  33. Beggs, H.E., Baragona, S.C., Hemperly, J.J. & Maness, P.F. NCAM-140 interacts with the focal adhesion kinase p125fak and the src-related tyrosine kinase p59fyn. J. Biol. Chem. 272, 8310–8319 (1997).

    CAS  PubMed  Google Scholar 

  34. Schmid, R-S . et al. NCAM stimulates the Ras-MAPK pathway and CREB phosphorylation in neuronal cells. J. Neurobiol. 38, 542–555 (1999).

    CAS  PubMed  Google Scholar 

  35. Kolkova, K., Novitskaya, V., Pedersen, N., Berezin, V. & Bock, E. Neural cell adhesion molecule-stimulated neurite outgrowth depends on activation of protein kinase C and the Ras-mitogen-activated protein kinase pathway. J. Neurosci. 20, 2238–2246 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Jessen, U. et al. The transcription factors CREB and c-Fos play key roles in NCAM- mediated neuritogenesis in PC12–E2 cells. J. Neurochem. 79, 1149–1160 (2001).

    CAS  PubMed  Google Scholar 

  37. Krushel, L.A., Cunningham, B.A., Edelman, G.M. & Crossin, K.L. NF-κB activity is induced by neural cell adhesion molecule binding to neurons and astrocytes. J. Biol. Chem. 274, 2432–2439 (1999).

    CAS  PubMed  Google Scholar 

  38. Saffell, J.L., Williams, E.J., Mason, I.J., Walsh, F.S. & Doherty, P. Expression of a dominant negative FGF receptor inhibits axonal growth and FGF receptor phosphorylation stimulated by CAMs. Neuron 18, 231–242 (1997).

    CAS  PubMed  Google Scholar 

  39. Niethammer, P. et al. Cosignaling of NCAM via lipid rafts and the FGF receptor is required for neuritogenesis. J. Cell Biol. 157, 521–532 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Santuccione, A., Sytnyk, V., Leshchyns'ka, I. & Schachner, M. Prion protein recruits its neuronal receptor NCAM to lipid rafts to activate p59fyn and to enhance neurite outgrowth. J. Cell Biol. 169, 341–354 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Paratcha, G., Ledda, F. & Ibanez, C.F. The neural cell adhesion molecule NCAM is an alternative signaling receptor for GDNF family ligands. Cell 113, 867–879 (2003).

    CAS  PubMed  Google Scholar 

  42. Felding-Habermann, B. et al. A single immunoglobulin-like domain of the human neural cell adhesion molecule L1 supports adhesion by multiple vascular and platelet integrins. J. Cell Biol. 139, 1567–1581 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Thelen, K. et al. The neural cell adhesion molecule L1 potentiates integrin-dependent cell migration to extracellular matrix proteins. J. Neurosci. 22, 4918–4931 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Silletti, S., Mei, F., Sheppard, D. & Montgomery, A.M. Plasmin-sensitive dibasic sequences in the third fibronectin-like domain of L1-cell adhesion molecule (CAM) facilitate homomultimerization and concomitant integrin recruitment. J. Cell Biol. 149, 1485–1502 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Schaefer, A.W. et al. Activation of the MAPK signal cascade by the neural cell adhesion molecule L1 requires L1 internalization. J. Biol. Chem. 274, 37965–37973 (1999).

    CAS  PubMed  Google Scholar 

  46. Schmid, R.S., Pruitt, W.M. & Maness, P.F.A. MAP kinase signaling pathway mediates neurite outgrowth on L1 and requires Src-dependent endocytosis. J. Neurosci. 20, 4177–4188 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Schmid, R.S., Midkiff, B.R., Kedar, V.P. & Maness, P.F. Adhesion molecule L1 stimulates neuronal migration through Vav2-Pak1 signaling. Neuroreport 15, 2791–2794 (2004).

    CAS  PubMed  Google Scholar 

  48. Ridley, A.J. et al. Cell migration: integrating signals from front to back. Science 302, 1704–1709 (2003).

    CAS  PubMed  Google Scholar 

  49. Cheng, L., Lemmon, S. & Lemmon, V. RanBPM is an L1-interacting protein that regulates L1-mediated mitogen-activated protein kinase activation. J. Neurochem. 94, 1102–1110 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Silletti, S. et al. Extracellular signal-regulated kinase (ERK)-dependent gene expression contributes to L1 cell adhesion molecule-dependent motility and invasion. J. Biol. Chem. 279, 28880–28888 (2004).

    CAS  PubMed  Google Scholar 

  51. Demyanenko, G.P. et al. Close homolog of L1 modulates area-specific neuronal positioning and dendrite orientation in the cerebral cortex. Neuron 44, 423–437 (2004).

    CAS  PubMed  Google Scholar 

  52. Montag-Sallaz, M., Schachner, M. & Montag, D. Misguided axonal projections, neural cell adhesion molecule 180 mRNA upregulation, and altered behavior in mice deficient for the close homolog of L1. Mol. Cell. Biol. 22, 7967–7981 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Demyanenko, G., Tsai, A. & Maness, P.F. Abnormalities in neuronal process extension, hippocampal development, and the ventricular system of L1 knockout mice. J. Neurosci. 19, 4907–4920 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Buhusi, M. et al. Close homolog of L1 is an enhancer of integrin-mediated cell migration. J. Biol. Chem. 278, 25024–25031 (2003).

    CAS  PubMed  Google Scholar 

  55. Pratte, M., Rougon, G., Schachner, M. & Jamon, M. Mice deficient for the close homologue of the neural adhesion cell L1 (CHL1) display alterations in emotional reactivity and motor coordination. Behav. Brain Res. 147, 31–39 (2003).

    CAS  PubMed  Google Scholar 

  56. Irintchev, A., Koch, M., Needham, L.K., Maness, P. & Schachner, M. Impairment of sensorimotor gating in mice deficient in the cell adhesion molecule L1 or its close homologue, CHL1. Brain Res. 1029, 131–134 (2004).

    CAS  PubMed  Google Scholar 

  57. Lindner, J., Rathjen, F.G. & Schachner, M. L1 mono- and polyclonal antibodies modify cell migration in early post-natal mouse cerebellum. Nature 305, 427–430 (1983).

    CAS  PubMed  Google Scholar 

  58. Sakurai, T. et al. Overlapping functions of the cell adhesion molecules Nr-CAM and L1 in cerebellar granule cell development. J. Cell Biol. 154, 1259–1273 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Diestel, S., Hinkle, C.L., Schmitz, B. & Maness, P.F. NCAM140 stimulates integrin-dependent cell migration by ectodomain shedding. J. Neurochem. 95, 1777–1784 (2005).

    CAS  PubMed  Google Scholar 

  60. Hubschmann, M.V., Skladchikova, G., Bock, E. & Berezin, V. Neural cell adhesion molecule function is regulated by metalloproteinase-mediated ectodomain release. J. Neurosci. Res. 80, 826–837 (2005).

    PubMed  Google Scholar 

  61. Hinkle, C.L., Diestel, S., Lieberman, J. & Maness, P.F. Metalloprotease-induced ectodomain shedding of neural cell adhesion molecule (NCAM). J. Neurobiol. 66, 1378–1395 (2006).

    CAS  PubMed  Google Scholar 

  62. Kalus, I., Bormann, U., Mzoughi, M., Schachner, M. & Kleene, R. Proteolytic cleavage of the neural cell adhesion molecule by ADAM17/TACE is involved in neurite outgrowth. J. Neurochem. 98, 78–88 (2006).

    CAS  PubMed  Google Scholar 

  63. Mechtersheimer, S. et al. Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins. J. Cell Biol. 155, 661–673 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Maretzky, T. et al. L1 is sequentially processed by two differently activated metalloproteases and Presenilin/gamma-secretase and regulates neural cell adhesion, cell migration, and neurite outgrowth. Mol. Cell. Biol. 25, 9040–9053 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Kalus, I., Schnegelsberg, B., Seidah, N.G., Kleene, R. & Schachner, M. The proprotein convertase PC5A and a metalloprotease are involved in the proteolytic processing of the neural adhesion molecule L1. J. Biol. Chem. 278, 10381–10388 (2003).

    CAS  PubMed  Google Scholar 

  66. Gutwein, P. et al. Role of Src kinases in the ADAM-mediated release of L1 adhesion molecule from human tumor cells. J. Biol. Chem. 275, 15490–15497 (2000).

    CAS  PubMed  Google Scholar 

  67. Heiz, M., Grunberg, J., Schubiger, P.A. & Novak-Hofer, I. Hepatocyte growth factor-induced ectodomain shedding of cell adhesion molecule L1: role of the L1 cytoplasmic domain. J. Biol. Chem. 279, 31149–31156 (2004).

    CAS  PubMed  Google Scholar 

  68. Naus, S. et al. Ectodomain shedding of the neural recognition molecule CHL1 by the metalloprotease-disintegrin ADAM8 promotes neurite outgrowth and suppresses neuronal cell death. J. Biol. Chem. 279, 16083–16090 (2004).

    CAS  PubMed  Google Scholar 

  69. Kamiguchi, H. & Lemmon, V. Recycling of the cell adhesion molecule L1 in axonal growth cones. J. Neurosci. 20, 3676–3686 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Schaefer, A.W. et al. L1 endocytosis is controlled by a phosphorylation-dephosphorylation cycle stimulated by outside-in signaling by L1. J. Cell Biol. 157, 1223–1232 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Panicker, A.K., Buhusi, M., Erickson, A. & Maness, P.F. Endocytosis of β1 integrins is an early event in migration promoted by the cell adhesion molecule L1. Exp. Cell Res. 312, 299–307 (2006).

    CAS  PubMed  Google Scholar 

  72. Cohen, N.R. et al. Errors in corticospinal axon guidance in mice lacking the neural cell adhesion molecule L1. Curr. Biol. 8, 26–33 (1998).

    CAS  PubMed  Google Scholar 

  73. Rolf, B., Bastmeyer, M., Schachner, M. & Bartsch, U. Pathfinding errors of corticospinal axons in neural cell adhesion molecule-deficient mice. J. Neurosci. 22, 8357–8362 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Castellani, V., Chedotal, A., Schachner, M., Faivre-Sarrailh, C. & Rougon, G. Analysis of the L1-deficient mouse phenotype reveals cross-talk between Sema3A and L1 signaling pathways in axonal guidance. Neuron 27, 237–249 (2000).

    CAS  PubMed  Google Scholar 

  75. Fournier, A.E. et al. Semaphorin3A enhances endocytosis at sites of receptor-F-actin colocalization during growth cone collapse. J. Cell Biol. 149, 411–422 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Castellani, V., Falk, J. & Rougon, G. Semaphorin3A-induced receptor endocytosis during axon guidance responses is mediated by L1 CAM. Mol. Cell. Neurosci. 26, 89–100 (2004).

    CAS  PubMed  Google Scholar 

  77. Wiencken-Barger, A.E., Mavity-Hudson, J., Bartsch, U., Schachner, M. & Casagrande, V.A. The role of L1 in axon pathfinding and fasciculation. Cereb. Cortex 14, 121–131 (2004).

    CAS  PubMed  Google Scholar 

  78. Demyanenko, G.P. & Maness, P.F. The L1 cell adhesion molecule is essential for topographic mapping of retinal axons. J. Neurosci. 23, 530–538 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Feldheim, D.A. et al. Genetic analysis of ephrin-A2 and ephrin-A5 shows their requirement in multiple aspects of retinocollicular mapping. Neuron 25, 563–574 (2000).

    CAS  PubMed  Google Scholar 

  80. Williams, S.E. et al. A role for Nr-CAM in the patterning of binocular visual pathways. Neuron 50, 535–547 (2006).

    CAS  PubMed  Google Scholar 

  81. Williams, S.E. et al. Ephrin-B2 and EphB1 mediate retinal axon divergence at the optic chiasm. Neuron 39, 919–935 (2003).

    CAS  PubMed  Google Scholar 

  82. Bodrikov, V. et al. RPTPalpha is essential for NCAM-mediated p59fyn activation and neurite elongation. J. Cell Biol. 168, 127–139 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Leshchyns'ka, I., Sytnyk, V., Morrow, J.S. & Schachner, M. Neural cell adhesion molecule (NCAM) association with PKCβ2 via βI spectrin is implicated in NCAM-mediated neurite outgrowth. J. Cell Biol. 161, 625–639 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Needham, L.K., Thelen, K. & Maness, P.F. Cytoplasmic domain mutations of the L1 cell adhesion molecule reduce L1-ankyrin interactions. J. Neurosci. 21, 1490–1500 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Garver, T.D., Ren, Q., Tuvia, S. & Bennett, V. Tyrosine phosphorylation at a site highly conserved in the L1 family of cell adhesion molecules abolishes ankyrin binding and increases lateral mobility of neurofascin. J. Cell Biol. 137, 703–714 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Kizhatil, K., Wu, Y.X., Sen, A. & Bennett, V. A new activity of doublecortin in recognition of the phospho-Fig.Y tyrosine in the cytoplasmic domain of neurofascin. J. Neurosci. 22, 7948–7958 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Whittard, J.D., Sakurai, T., Cassella, M.R., Gazdoiu, M. & Felsenfeld, D.P. MAP kinase pathway-dependent phosphorylation of the L1-CAM ankyrin binding site regulates neuronal growth. Mol. Biol. Cell 17, 2696–2706 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Gil, O.D. et al. Ankyrin binding mediates L1CAM interactions with static components of the cytoskeleton and inhibits retrograde movement of L1CAM on the cell surface. J. Cell Biol. 162, 719–730 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Nishimura, K. et al. L1-dependent neuritogenesis involves ankyrinB that mediates L1-CAM coupling with retrograde actin flow. J. Cell Biol. 163, 1077–1088 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Nakai, Y. & Kamiguchi, H. Migration of nerve growth cones requires detergent-resistant membranes in a spatially defined and substrate-dependent manner. J. Cell Biol. 159, 1097–1108 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Schafer, D.P., Bansal, R., Hedstrom, K.L., Pfeiffer, S.E. & Rasband, M.N. Does paranode formation and maintenance require partitioning of neurofascin 155 into lipid rafts? J. Neurosci. 24, 3176–3185 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Falk, J., Thoumine, O., Dequidt, C., Choquet, D. & Faivre-Sarrailh, C. NrCAM coupling to the cytoskeleton depends on multiple protein domains and partitioning into lipid rafts. Mol. Biol. Cell 15, 4695–4709 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Ango, F. et al. Ankyrin-based subcellular gradient of neurofascin, an immunoglobulin family protein, directs GABAergic innervation at purkinje axon initial segment. Cell 119, 257–272 (2004).

    CAS  PubMed  Google Scholar 

  94. Pillai-Nair, N. et al. Neural cell adhesion molecule-secreting transgenic mice display abnormalities in GABAergic interneurons and alterations in behavior. J. Neurosci. 25, 4659–4671 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Huang, Z.J. Subcellular organization of GABAergic synapses: role of ankyrins and L1 cell adhesion molecules. Nat. Neurosci. 9, 163–166 (2006).

    CAS  PubMed  Google Scholar 

  96. Cheng, L., Itoh, K. & Lemmon, V. L1-mediated branching is regulated by two ezrin-radixin-moesin (ERM)-binding sites, the RSLE region and a novel juxtamembrane ERM-binding region. J. Neurosci. 25, 395–403 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Mintz, C.D., Dickson, T.C., Gripp, M.L., Salton, S.R. & Benson, D.L. ERMs colocalize transiently with L1 during neocortical axon outgrowth. J. Comp. Neurol. 464, 438–448 (2003).

    CAS  PubMed  Google Scholar 

  98. Nelson, W.J. & Nusse, R. Convergence of Wnt, β-catenin, and cadherin pathways. Science 303, 1483–1487 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Franco, S.J. & Huttenlocher, A. Regulating cell migration: calpains make the cut. J. Cell Sci. 118, 3829–3838 (2005).

    CAS  PubMed  Google Scholar 

  100. Higashida, C. et al. Actin polymerization-driven molecular movement of mDia1 in living cells. Science 303, 2007–2010 (2004).

    CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by grants from the US National Institutes of Health NS049109, MH064056 (Silvio Conte Center for Neuroscience of Mental Disorders), National Science Foundation NSF0618176 to P.F.M. and grants from the Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, and the European Community to M.S.

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Correspondence to Patricia F Maness.

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Maness, P., Schachner, M. Neural recognition molecules of the immunoglobulin superfamily: signaling transducers of axon guidance and neuronal migration. Nat Neurosci 10, 19–26 (2007). https://doi.org/10.1038/nn1827

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