Role of CRMP-2 in Neuronal Polarization

  • Nariko Arimura
  • Takeshi oshimura
  • Kozo Kaibuchi


Hippocampal Neuron Dorsal Root Ganglion Neuron Growth Cone Neuronal Polarization Growth Cone Collapse 
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  1. Abe, T., Kato, M., Miki, H., Takenawa, T., and Endo, T., 2003, Small GTPase Tc10 and its homologue RhoT induce N-WASP-mediated long process formation and neurite outgrowth, J. Cell Sci. 116: 155–168.PubMedCrossRefGoogle Scholar
  2. Amano, M., Chihara, K., Nakamura, N., Fukata, Y., Yano, T., Shibata, M., et al., 1998, Myosin II activation promotes neurite retraction during the action of Rho and Rho-kinase, Genes Cells 3: 177–188.PubMedCrossRefGoogle Scholar
  3. Arimura, N., Inagaki, N., Chihara, K., Menager, C., Nakamura, N., Amano, M., et al., 2000, Phosphorylation of collapsin response mediator protein-2 by Rho-kinase. Evidence for two separate signaling pathways for growth cone collapse, J. Biol. Chem. 275: 23973–23980.PubMedCrossRefGoogle Scholar
  4. Arimura, N., Menager, C., Kawano, Y., Yoshimura, T., Kawabata, S., Hattori, A., et al., 2005, Phosphorylation by Rho kinase regulates CRMP-2 activity in growth cones, Mol. Cell Biol. 25: 9973–9984.PubMedCrossRefGoogle Scholar
  5. Baas, P.W., and Buster, D.W., 2004, Slow axonal transport and the genesis of neuronal morphology, J. Neurobiol. 58: 3–17.PubMedCrossRefGoogle Scholar
  6. Berdnik, D., Torok, T., Gonzalez-Gaitan, M., and Knoblich, J.A., 2002, The endocytic protein α-Adaptin is required for numb-mediated asymmetric cell division in Drosophila, Dev. Cell 3: 221–231.PubMedCrossRefGoogle Scholar
  7. Bradke, F., and Dotti, C.G., 2000, Establishment of neuronal polarity: Lessons from cultured hippocampal neurons, Curr. Opin. Neurobiol. 10: 574–581.PubMedCrossRefGoogle Scholar
  8. Brady, S.T., 1985, A novel brain ATPase with properties expected for the fast axonal transport motor, Nature 317: 73–75.PubMedCrossRefGoogle Scholar
  9. Brown, M., Jacobs, T., Eickholt, B., Ferrari, G., Teo, M., Monfries, C., et al., 2004, a2-chimaerin, cyclin-dependent Kinase 5/p35, and its target collapsin response mediator protein-2 are essential components in semaphorin 3A-induced growth-cone collapse, J. Neurosci. 24: 8994–9004.PubMedCrossRefGoogle Scholar
  10. Byk, T., Ozon, S., and Sobel, A., 1998, The Ulip family phosphoproteins: Common and specific properties, Eur. J. Biochem. 254: 14–24.PubMedCrossRefGoogle Scholar
  11. Chen, X., and Macara, I.G., 2005, Par-3 controls tight junction assembly through the Rac exchange factor Tiam1, Nat. Cell Biol. 7: 262–269.PubMedCrossRefGoogle Scholar
  12. Chuang, J.Z., Yeh, T.Y., Bollati, F., Conde, C., Canavosio, F., Caceres, A., et al., 2005, The dynein light chain Tctex-1 has a dynein-independent role in actin remodeling during neurite outgrowth, Dev. Cell 9: 75–86.PubMedCrossRefGoogle Scholar
  13. Cole, A.R., Knebel, A., Morrice, N.A., Robertson, L.A., Irving, A.J., Connolly, C.N., et al., 2004, GSK-3 phosphorylation of the Alzheimer epitope within collapsin response mediator proteins regulates axon elongation in primary neurons, J. Biol. Chem. 279: 50176–50180.PubMedCrossRefGoogle Scholar
  14. Craig, A.M., and Banker, G., 1994, Neuronal polarity, Annu. Rev. Neurosci. 17: 267–310.PubMedCrossRefGoogle Scholar
  15. De Camilli, P., Emr, S.D., McPherson, P.S., and Novick, P., 1996, Phosphoinositides as regulators in membrane traffic, Science 271: 1533–1539.PubMedCrossRefGoogle Scholar
  16. Dickson, B., Sprenger, F., Morrison, D., and Hafen, E., 1992, Raf functions downstream of Ras1 in the Sevenless signal transduction pathway, Nature 360: 600–603.PubMedCrossRefGoogle Scholar
  17. Dotti, C.G., Sullivan, C.A., and Banker, G.A., 1988, The establishment of polarity by hippocampal neurons in culture, J. Neurosci. 8: 1454–1468.PubMedGoogle Scholar
  18. Eldar-Finkelman, H., 2002, Glycogen synthase kinase 3: An emerging therapeutic target, Trends Mol. Med. 8: 126–132.PubMedCrossRefGoogle Scholar
  19. Esch, T., Lemmon, V., and Banker, G., 1999, Local presentation of substrate molecules directs axon specification by cultured hippocampal neurons, J. Neurosci. 19: 6417–6426.PubMedGoogle Scholar
  20. Frame, S., and Cohen, P., 2001, GSK3 takes centre stage more than 20 years after its discovery, Biochem. J. 359: 1–16.PubMedCrossRefGoogle Scholar
  21. Fukata, Y., Itoh, T.J., Kimura, T., Menager, C., Nishimura, T., Shiromizu, T., et al., 2002, CRMP-2 binds to tubulin heterodimers to promote microtubule assembly, Nat. Cell Biol. 4: 583–591.PubMedGoogle Scholar
  22. Gaetano, C., Matsuo, T., and Thiele, C.J., 1997, Identification and characterization of a retinoic acid-regulated human homologue of the unc-33-like phosphoprotein gene (hUlip) from neuroblastoma cells, J. Biol. Chem. 272: 12195–12201.PubMedCrossRefGoogle Scholar
  23. Goold, R.G., Owen, R., and Gordon-Weeks, P.R., 1999, Glycogen synthase kinase 3b phosphorylation of microtubule-associated protein 1B regulates the stability of microtubules in growth cones, J. Cell Sci. 112: 3373–3384.PubMedGoogle Scholar
  24. Goshima, Y., Nakamura, F., Strittmatter, P., and Strittmatter, S.M., 1995, Collapsin-induced growth cone collapse mediated by an intracellular protein related to UNC-33, Nature 376: 509–514.PubMedCrossRefGoogle Scholar
  25. Govek, E.E., Newey, S.E., and Van Aelst, L., 2005, The role of the Rho GTPases in neuronal development, Genes Dev. 19: 1–49.PubMedCrossRefGoogle Scholar
  26. Hamajima, N., Matsuda, K., Sakata, S., Tamaki, N., Sasaki, M., and Nonaka, M., 1996, A novel gene family defined by human dihydropyrimidinase and three related proteins with differential tissue distribution, Gene 180: 157–163.PubMedCrossRefGoogle Scholar
  27. Hancock, J.F., 2003, Ras proteins: Different signals from different locations, Nat. Rev. Mol. Cell Biol. 4: 373–384.PubMedCrossRefGoogle Scholar
  28. Hannigan, G., Troussard, A.A., and Dedhar, S., 2005, Integrin-linked kinase: A cancer therapeutic target unique among its ILK, Nat. Rev. Cancer 5: 51–63.PubMedCrossRefGoogle Scholar
  29. Hedgecock, E.M., Culotti, J.G., Thomson, J.N., and Perkins, L.A., 1985, Axonal guidance mutants of Caenorhabditis elegans identified by filling sensory neurons with fluorescein dyes, Dev. Biol. 111: 158–170.PubMedCrossRefGoogle Scholar
  30. Hirokawa, N., and Takemura, R., 2005, Molecular motors and mechanisms of directional transport in neurons, Nat. Rev. Neurosci. 6: 201–214.PubMedCrossRefGoogle Scholar
  31. Iijima, M., Huang, Y.E., and Devreotes, P., 2002, Temporal and spatial regulation of chemotaxis, Dev. Cell 3: 469–478.PubMedCrossRefGoogle Scholar
  32. Inagaki, N., Chihara, K., Arimura, N., Menager, C., Kawano, Y., Matsuo, N., et al., 2001, CRMP-2 induces axons in cultured hippocampal neurons, Nat. Neurosci. 4: 781–782.PubMedCrossRefGoogle Scholar
  33. Jalink, K., van Corven, E.J., Hengeveld, T., Morii, N., Narumiya, S., and Moolenaar, W.H., 1994, Inhibition of lysophosphatidate- and thrombin-induced neurite retraction and neuronal cell rounding by ADP ribosylation of the small GTP-binding protein Rho, J. Cell Biol. 126: 801–810.PubMedCrossRefGoogle Scholar
  34. Jiang, H., Guo, W., Liang, X., and Rao, Y., 2005, Both the establishment and the maintenance of neuronal polarity require active mechanisms: Critical roles of GSK-3β and its upstream regulators, Cell 120: 123–135.PubMedGoogle Scholar
  35. Jimbo, T., Kawasaki, Y., Koyama, R., Sato, R., Takada, S., Haraguchi, K., et al., 2002, Identification of a link between the tumour suppressor APC and the kinesin superfamily, Nat. Cell Biol. 4: 323–327.PubMedCrossRefGoogle Scholar
  36. Johnson, C.S., Buster, D., and Scholey, J.M., 1990, Light chains of sea urchin kinesin identified by immunoadsorption, Cell Motil. Cytoskeleton 16: 204–213.PubMedCrossRefGoogle Scholar
  37. Kamal, A., and Goldstein, L.S., 2002, Principles of cargo attachment to cytoplasmic motor proteins, Curr. Opin. Cell Biol. 14: 63–68.PubMedCrossRefGoogle Scholar
  38. Kamal, A., Stokin, G.B., Yang, Z., Xia, C.H., and Goldstein, L.S., 2000, Axonal transport of amyloid precursor protein is mediated by direct binding to the kinesin light chain subunit of kinesin-I, Neuron 28: 449–459.PubMedCrossRefGoogle Scholar
  39. Kawano, Y., Yoshimura, T., Tsuboi, D., Kawabata, S., Kaneko-Kawano, T., Shirataki, H., et al., 2005, CRMP-2 Is involved in kinesin-1-dependent transport of the Sra-1/WAVE1 complex and axon formation, Mol. Cell Biol. 25: 9920–9935.PubMedCrossRefGoogle Scholar
  40. Kimura, T., Arimura, N., Fukata, Y., Watanabe, H., Iwamatsu, A., and Kaibuchi, K., 2005, Tubulin and CRMP-2 complex is transported via Kinesin-1, J. Neurochem. 93: 1371–1382.PubMedCrossRefGoogle Scholar
  41. Kobayashi, K., Kuroda, S., Fukata, M., Nakamura, N., Nagase, T., Nomura, N., et al., 1998, p140Sra-1 (specifically Rac1-associated protein) is a novel specific target for Rac1 small GTPase, J. Biol. Chem. 273: 291–295.PubMedCrossRefGoogle Scholar
  42. Kunda, P., Paglini, G., Quiroga, S., Kosik, K., and Caceres, A., 2001, Evidence for the involvement of Tiam1 in axon formation, J. Neurosci. 21: 2361–2372.PubMedGoogle Scholar
  43. Li, W., Herman, R.K., and Shaw, J.E., 1992, Analysis of the Caenorhabditis elegans axonal guidance and outgrowth gene unc-33, Genetics 132: 675–689.PubMedGoogle Scholar
  44. Luo, L., Liao, Y.J., Jan, L.Y., and Jan, Y.N., 1994, Distinct morphogenetic functions of similar small GTPases: Drosophila Drac1 is involved in axonal outgrowth and myoblast fusion, Genes Dev. 8: 1787–1802.PubMedCrossRefGoogle Scholar
  45. Menager, C., Arimura, N., Fukata, Y., and Kaibuchi, K., 2004, PIP3 is involved in neuronal polarization and axon formation, J. Neurochem. 89: 109–118.PubMedCrossRefGoogle Scholar
  46. Minturn, J.E., Fryer, H.J., Geschwind, D.H., and Hockfield, S., 1995, TOAD-64, a gene expressed early in neuronal differentiation in the rat, is related to unc-33, a C. elegans gene involved in axon outgrowth, J. Neurosci. 15: 6757–6766.PubMedGoogle Scholar
  47. Nishimura, T., Fukata, Y., Kato, K., Yamaguchi, T., Matsuura, Y., Kamiguchi, H., et al., 2003, CRMP-2 regulates polarized Numb-mediated endocytosis for axon growth, Nat. Cell Biol. 5: 819–826.PubMedCrossRefGoogle Scholar
  48. Nishimura, T., Kato, K., Yamaguchi, T., Fukata, Y., Ohno, S., and Kaibuchi, K., 2004, Role of the PAR-3-KIF3 complex in the establishment of neuronal polarity, Nat. Cell Biol. 6: 328–334.PubMedCrossRefGoogle Scholar
  49. Nishimura, T., Yamaguchi, T., Kato, K., Yoshizawa, M., Nabeshima, Y., Ohno, S., et al., 2005, PAR-6-PAR-3 mediates Cdc42-induced Rac activation through the Rac GEFs STEF/Tiam1, Nat. Cell Biol. 7: 270–277.PubMedCrossRefGoogle Scholar
  50. Ohno, S., 2001, Intercellular junctions and cellular polarity: The PAR-aPKC complex, a conserved core cassette playing fundamental roles in cell polarity, Curr. Opin. Cell Biol. 13: 641–648.PubMedCrossRefGoogle Scholar
  51. Rodriguez-Viciana, P., Warne, P.H., Dhand, R., Vanhaesebroeck, B., Gout, I., Fry, M.J., et al., 1994, Phosphatidylinositol-3-OH kinase as a direct target of Ras, Nature 370: 527–532.PubMedCrossRefGoogle Scholar
  52. Rolls, M.M., and Doe, C.Q., 2004, Baz, Par-6 and aPKC are not required for axon or dendrite specification in Drosophila, Nat. Neurosci. 7: 1293–1295.PubMedCrossRefGoogle Scholar
  53. Salcini, A.E., Confalonieri, S., Doria, M., Santolini, E., Tassi, E., Minenkova, O., et al., 1997, Binding specificity and in vivo targets of the EH domain, a novel protein-protein interaction module, Genes Dev. 11: 2239–2249.PubMedCrossRefGoogle Scholar
  54. Santolini, E., Puri, C., Salcini, A.E., Gagliani, M.C., Pelicci, P.G., Tacchetti, C., et al., 2000, Numb is an endocytic protein, J. Cell Biol. 151: 1345–1352.PubMedCrossRefGoogle Scholar
  55. Schenck, A., Bardoni, B., Langmann, C., Harden, N., Mandel, J.L., and Giangrande, A., 2003, CYFIP/Sra-1 controls neuronal connectivity in Drosophila and links the Rac1 GTPase pathway to the fragile X protein, Neuron 38: 887–898.PubMedCrossRefGoogle Scholar
  56. Schwamborn, J.C., and Puschel, A.W., 2004, The sequential activity of the GTPases Rap1B and Cdc42 determines neuronal polarity, Nat. Neurosci. 7: 923–929.PubMedCrossRefGoogle Scholar
  57. Setou, M., Seog, D.H., Tanaka, Y., Kanai, Y., Takei, Y., Kawagishi, M., et al., 2002, Glutamate-receptor-interacting protein GRIP1 directly steers kinesin to dendrites, Nature 417: 83–87.PubMedCrossRefGoogle Scholar
  58. Shi, S.H., Jan, L.Y., and Jan, Y.N., 2003, Hippocampal neuronal polarity specified by spatially localized mPar3/mPar6 and PI 3-kinase activity, Cell 112: 63–75.PubMedCrossRefGoogle Scholar
  59. Takei, Y., Teng, J., Harada, A., and Hirokawa, N., 2000, Defects in axonal elongation and neuronal migration in mice with disrupted tau and map1b genes, J. Cell Biol. 150: 989–1000.PubMedCrossRefGoogle Scholar
  60. Trivedi, N., Marsh, P., Goold, R.G., Wood-Kaczmar, A., and Gordon-Weeks, P.R., 2005, Glycogen synthase kinase-3b phosphorylation of MAP1B at Ser1260 and Thr1265 is spatially restricted to growing axons, J. Cell Sci. 118: 993–1005.PubMedCrossRefGoogle Scholar
  61. Uchida, Y., Ohshima, T., Sasaki, Y., Suzuki, H., Yanai, S., Yamashita, N., et al., 2005, Semaphorin3A signalling is mediated via sequential Cdk5 and GSK3β phosphorylation of CRMP2: Implication of common phosphorylating mechanism underlying axon guidance and Alzheimer's disease, Genes Cells 10: 165–179.PubMedCrossRefGoogle Scholar
  62. Vale, R.D., Reese, T.S., and Sheetz, M.P., 1985, Identification of a novel force-generating protein, kinesin, involved in microtubule-based motility, Cell 42: 39–50.PubMedCrossRefGoogle Scholar
  63. Varnai, P., and Balla, T., 1998, Visualization of phosphoinositides that bind pleckstrin homology domains: Calcium- and agonist-induced dynamic changes and relationship to myo-[3H]inositol-labeled phosphoinositide pools, J. Cell Biol. 143: 501–510.PubMedCrossRefGoogle Scholar
  64. Verhey, K.J., Meyer, D., Deehan, R., Blenis, J., Schnapp, B.J., Rapoport, T.A., et al., 2001, Cargo of kinesin identified as JIP scaffolding proteins and associated signaling molecules, J. Cell Biol. 152: 959–970.PubMedCrossRefGoogle Scholar
  65. Vojtek, A.B., Hollenberg, S.M., and Cooper, J.A., 1993, Mammalian Ras interacts directly with the serine/threonine kinase Raf, Cell 74: 205–214.PubMedCrossRefGoogle Scholar
  66. Wang, L.H., and Strittmatter, S.M., 1996, A family of rat CRMP genes is differentially expressed in the nervous system, J. Neurosci. 16: 6197–6207.PubMedGoogle Scholar
  67. Wiggin, G.R., Fawcett, J.P., and Pawson, T., 2005, Polarity proteins in axon specification and synaptogenesis, Dev. Cell 8: 803–816.PubMedCrossRefGoogle Scholar
  68. Yoshimura, T., Kawano, Y., Arimura, N., Kawabata, S., Kikuchi, A., and Kaibuchi, K., 2005a, GSK-3β regulates phosphorylation of CRMP-2 and neuronal polarity, Cell 120: 137–149.PubMedCrossRefGoogle Scholar
  69. Yoshimura, T., Arimura, N., Kawano, Y., Kawabata, S., Wang, S., and Kaibuchi, K., 2006, Ras regulates neuronal polarity via the PI 3-kinase/Akt/GSK-3β/CRMP-2 pathway, Biochem. Biophys. Res. Comm. 340: 62–68.PubMedCrossRefGoogle Scholar
  70. Zallen, J.A., Cohen, Y., Hudson, A.M., Cooley, L., Wieschaus, E., and Schejter, E.D., 2002, SCAR is a primary regulator of Arp2/3-dependent morphological events in Drosophila, J. Cell Biol. 156: 689–701.PubMedCrossRefGoogle Scholar
  71. Zumbrunn, J., Kinoshita, K., Hyman, A.A., and Nathke, I.S., 2001, Binding of the adenomatous polyposis coli protein to microtubules increase microtubule stability and is regulated by GSK3 phosphorylation, Curr. Biol. 11: 44–49.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Nariko Arimura
    • 1
  • Takeshi oshimura
    • 2
  • Kozo Kaibuchi
    • 3
  1. 1.Department of Cell Pharmacology, Graduate School of MedicineNagoya UniversityShowa-kuJapan
  2. 2.Department of Cell Pharmacology, Graduate School of MedicineNagoya UniversityShowa-kuJapan
  3. 3.Department of Cell Pharmacology, Graduate School of MedicineNagoya UniversityShowa-kuJapan

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