Skip to main content
Log in

Collapsin Response Mediator Proteins Regulate Neuronal Development and Plasticity by Switching Their Phosphorylation Status

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Collapsin response mediator protein (CRMP) was originally identified as a molecule involved in semaphorin3A signaling. CRMPs are now known to consist of five homologous cytosolic proteins, CRMP1–5. All of them are phosphorylated and highly expressed in the developing and adult nervous system. In vitro experiments have clearly demonstrated that CRMPs play important roles in neuronal development and maturation through the regulation of their phosphorylation. Several recent knockout mice studies have revealed in vivo roles of CRMPs in neuronal migration, neuronal network formation, synapse formation, synaptic plasticity, and neuronal diseases. Dynamic spatiotemporal regulation of phosphorylation status of CRMPs is involved in many aspects of neuronal development.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Luo L (2000) Rho GTPases in neuronal morphogenesis. Nat Rev Neurosci 1(3):173–180

    Article  PubMed  CAS  Google Scholar 

  2. Tessier-Lavigne M, Goodman CS (1996) The molecular biology of axon guidance. Science 274(5290):1123–1133

    Article  PubMed  CAS  Google Scholar 

  3. Poulain FE, Sobel A (2010) The microtubule network and neuronal morphogenesis: dynamic and coordinated orchestration through multiple players. Mol Cell Neurosci 43(1):15–32

    Article  PubMed  CAS  Google Scholar 

  4. Goshima Y, Nakamura F, Strittmatter P, Strittmatter SM (1995) Collapsin-induced growth cone collapse mediated by an intracellular protein related to UNC-33. Nature 376(6540):509–514

    Article  PubMed  CAS  Google Scholar 

  5. Byk T, Dobransky T, Cifuentes-Diaz C, Sobel A (1996) Identification and molecular characterization of Unc-33-like phosphoprotein (Ulip), a putative mammalian homolog of the axonal guidance-associated unc-33 gene product. J Neurosci 16(2):688–701

    PubMed  CAS  Google Scholar 

  6. Fukada M, Watakabe I, Yuasa-Kawada J, Kawachi H, Kuroiwa A, Matsuda Y, Noda M (2000) Molecular characterization of CRMP5, a novel member of the collapsin response mediator protein family. J Biol Chem 275(48):37957–37965

    Article  PubMed  CAS  Google Scholar 

  7. Hamajima N, Matsuda K, Sakata S, Tamaki N, Sasaki M, Nonaka M (1996) A novel gene family defined by human dihydropyrimidinase and three related proteins with differential tissue distribution. Gene 180(1–2):157–163

    Article  PubMed  CAS  Google Scholar 

  8. Inatome R, Tsujimura T, Hitomi T, Mitsui N, Hermann P, Kuroda S, Yamamura H, Yanagi S (2000) Identification of CRAM, a novel unc-33 gene family protein that associates with CRMP3 and protein-tyrosine kinase(s) in the developing rat brain. J Biol Chem 275(35):27291–27302

    PubMed  CAS  Google Scholar 

  9. Minturn JE, Fryer HJ, Geschwind DH, 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(10):6757–6766

    PubMed  CAS  Google Scholar 

  10. Wang LH, Strittmatter SM (1996) A family of rat CRMP genes is differentially expressed in the nervous system. J Neurosci 16(19):6197–6207

    PubMed  CAS  Google Scholar 

  11. Yuasa-Kawada J, Suzuki R, Kano F, Ohkawara T, Murata M, Noda M (2003) Axonal morphogenesis controlled by antagonistic roles of two CRMP subtypes in microtubule organization. Eur J Neurosci 17(11):2329–2343

    Article  PubMed  Google Scholar 

  12. Li W, Herman RK, Shaw JE (1992) Analysis of the Caenorhabditis elegans axonal guidance and outgrowth gene unc-33. Genetics 132(3):675–689

    PubMed  CAS  Google Scholar 

  13. Deo RC, Schmidt EF, Elhabazi A, Togashi H, Burley SK, Strittmatter SM (2004) Structural bases for CRMP function in plexin-dependent semaphorin3A signaling. Embo J 23(1):9–22

    Article  PubMed  CAS  Google Scholar 

  14. Majava V, Loytynoja N, Chen WQ, Lubec G, Kursula P (2008) Crystal and solution structure, stability and post-translational modifications of collapsin response mediator protein 2. Febs J 275(18):4583–4596

    Article  PubMed  CAS  Google Scholar 

  15. Stenmark P, Ogg D, Flodin S, Flores A, Kotenyova T, Nyman T, Nordlund P, Kursula P (2007) The structure of human collapsin response mediator protein 2, a regulator of axonal growth. J Neurochem 101(4):906–917

    Article  PubMed  CAS  Google Scholar 

  16. Hensley K, Venkova K, Christov A, Gunning W, Park J (2011) Collapsin response mediator protein-2: an emerging pathologic feature and therapeutic target for neurodisease indications. Mol Neurobiol 43(3):180–191

    Article  PubMed  CAS  Google Scholar 

  17. Fukata Y, Itoh TJ, Kimura T, Menager C, Nishimura T, Shiromizu T, Watanabe H, Inagaki N, Iwamatsu A, Hotani H, Kaibuchi K (2002) CRMP-2 binds to tubulin heterodimers to promote microtubule assembly. Nat Cell Biol 4(8):583–591

    PubMed  CAS  Google Scholar 

  18. Uchida Y, Ohshima T, Sasaki Y, Suzuki H, Yanai S, Yamashita N, Nakamura F, Takei K, Ihara Y, Mikoshiba K, Kolattukudy P, Honnorat J, Goshima Y (2005) Semaphorin3A signalling is mediated via sequential Cdk5 and GSK3beta phosphorylation of CRMP2: implication of common phosphorylating mechanism underlying axon guidance and Alzheimer's disease. Genes Cells 10(2):165–179

    Article  PubMed  CAS  Google Scholar 

  19. Yoshimura T, Kawano Y, Arimura N, Kawabata S, Kikuchi A, Kaibuchi K (2005) GSK-3beta regulates phosphorylation of CRMP-2 and neuronal polarity. Cell 120(1):137–149

    Article  PubMed  CAS  Google Scholar 

  20. Charrier E, Mosinger B, Meissirel C, Aguera M, Rogemond V, Reibel S, Salin P, Chounlamountri N, Perrot V, Belin MF, Goshima Y, Honnorat J, Thomasset N, Kolattukudy P (2006) Transient alterations in granule cell proliferation, apoptosis and migration in postnatal developing cerebellum of CRMP1(−/−) mice. Genes Cells 11(12):1337–1352

    Article  PubMed  CAS  Google Scholar 

  21. Quach TT, Massicotte G, Belin MF, Honnorat J, Glasper ER, Devries AC, Jakeman LB, Baudry M, Duchemin AM, Kolattukudy PE (2008) CRMP3 is required for hippocampal CA1 dendritic organization and plasticity. Faseb J 22(2):401–409

    Article  PubMed  CAS  Google Scholar 

  22. Su KY, Chien WL, Fu WM, Yu IS, Huang HP, Huang PH, Lin SR, Shih JY, Lin YL, Hsueh YP, Yang PC, Lin SW (2007) Mice deficient in collapsin response mediator protein-1 exhibit impaired long-term potentiation and impaired spatial learning and memory. J Neurosci 27(10):2513–2524

    Article  PubMed  CAS  Google Scholar 

  23. Yamashita N, Morita A, Uchida Y, Nakamura F, Usui H, Ohshima T, Taniguchi M, Honnorat J, Thomasset N, Takei K, Takahashi T, Kolattukudy P, Goshima Y (2007) Regulation of spine development by semaphorin3A through cyclin-dependent kinase 5 phosphorylation of collapsin response mediator protein 1. J Neurosci 27(46):12546–12554

    Article  PubMed  CAS  Google Scholar 

  24. Yamashita N, Mosinger B, Roy A, Miyazaki M, Ugajin K, Nakamura F, Sasaki Y, Yamaguchi K, Kolattukudy P, Goshima Y (2011) CRMP5 (collapsin response mediator protein 5) regulates dendritic development and synaptic plasticity in the cerebellar Purkinje cells. J Neurosci 31(5):1773–1779

    Article  PubMed  CAS  Google Scholar 

  25. Yamashita N, Uchida Y, Ohshima T, Hirai S, Nakamura F, Taniguchi M, Mikoshiba K, Honnorat J, Kolattukudy P, Thomasset N, Takei K, Takahashi T, Goshima Y (2006) Collapsin response mediator protein 1 mediates reelin signaling in cortical neuronal migration. J Neurosci 26(51):13357–13362

    Article  PubMed  CAS  Google Scholar 

  26. Niisato E, Nagai J, Yamashita N, Abe T, Kiyonari H, Goshima Y, Ohshima T (2012) CRMP4 suppresses apical dendrite bifurcation of CA1 pyramidal neurons in the mouse hippocampus. Dev Neurobiol. doi:10.1002/dneu.22007

  27. Yamashita N, Ohshima T, Nakamura F, Kolattukudy P, Honnorat J, Mikoshiba K, Goshima Y (2012) Phosphorylation of CRMP2 (collapsin response mediator protein 2) is involved in proper dendritic field organization. J Neurosci 32(4):1360–1365

    Article  PubMed  CAS  Google Scholar 

  28. Kriegstein AR, Noctor SC (2004) Patterns of neuronal migration in the embryonic cortex. Trends Neurosci 27(7):392–399

    Article  PubMed  CAS  Google Scholar 

  29. Bielas S, Higginbotham H, Koizumi H, Tanaka T, Gleeson JG (2004) Cortical neuronal migration mutants suggest separate but intersecting pathways. Annu Rev Cell Dev Biol 20:593–618

    Article  PubMed  CAS  Google Scholar 

  30. Gupta A, Tsai LH, Wynshaw-Boris A (2002) Life is a journey: a genetic look at neocortical development. Nat Rev Genet 3(5):342–355

    Article  PubMed  CAS  Google Scholar 

  31. Nadarajah B, Parnavelas JG (2002) Modes of neuronal migration in the developing cerebral cortex. Nat Rev Neurosci 3(6):423–432

    Article  PubMed  CAS  Google Scholar 

  32. Morita A, Yamashita N, Sasaki Y, Uchida Y, Nakajima O, Nakamura F, Yagi T, Taniguchi M, Usui H, Katoh-Semba R, Takei K, Goshima Y (2006) Regulation of dendritic branching and spine maturation by semaphorin3A-Fyn signaling. J Neurosci 26(11):2971–2980

    Article  PubMed  CAS  Google Scholar 

  33. Lambert de Rouvroit C, Goffinet AM (1998) The reeler mouse as a model of brain development. Adv Anat Embryol Cell Biol 150:1–106

    Article  PubMed  CAS  Google Scholar 

  34. Bock HH, Herz J (2003) Reelin activates SRC family tyrosine kinases in neurons. Curr Biol 13(1):18–26

    Article  PubMed  CAS  Google Scholar 

  35. Hiesberger T, Trommsdorff M, Howell BW, Goffinet A, Mumby MC, Cooper JA, Herz J (1999) Direct binding of Reelin to VLDL receptor and ApoE receptor 2 induces tyrosine phosphorylation of disabled-1 and modulates tau phosphorylation. Neuron 24(2):481–489

    Article  PubMed  CAS  Google Scholar 

  36. Howell BW, Herrick TM, Cooper JA (1999) Reelin-induced tryosine phosphorylation of disabled 1 during neuronal positioning. Genes Dev 13(6):643–648

    Article  PubMed  CAS  Google Scholar 

  37. Trommsdorff M, Gotthardt M, Hiesberger T, Shelton J, Stockinger W, Nimpf J, Hammer RE, Richardson JA, Herz J (1999) Reeler/disabled-like disruption of neuronal migration in knockout mice lacking the VLDL receptor and ApoE receptor 2. Cell 97(6):689–701

    Article  PubMed  CAS  Google Scholar 

  38. Howell BW, Herrick TM, Hildebrand JD, Zhang Y, Cooper JA (2000) Dab1 tyrosine phosphorylation sites relay positional signals during mouse brain development. Curr Biol 10(15):877–885

    Article  PubMed  CAS  Google Scholar 

  39. D'Arcangelo G, Miao GG, Chen SC, Soares HD, Morgan JI, Curran T (1995) A protein related to extracellular matrix proteins deleted in the mouse mutant reeler. Nature 374(6524):719–723

    Article  PubMed  Google Scholar 

  40. Uchida Y, Ohshima T, Yamashita N, Ogawara M, Sasaki Y, Nakamura F, Goshima Y (2009) Semaphorin3A signaling mediated by Fyn-dependent tyrosine phosphorylation of collapsin response mediator protein 2 at tyrosine 32. J Biol Chem 284(40):27393–27401

    Article  PubMed  CAS  Google Scholar 

  41. Rice DS, Sheldon M, D'Arcangelo G, Nakajima K, Goldowitz D, Curran T (1998) Disabled-1 acts downstream of Reelin in a signaling pathway that controls laminar organization in the mammalian brain. Development 125(18):3719–3729

    PubMed  CAS  Google Scholar 

  42. Yoneshima H, Nagata E, Matsumoto M, Yamada M, Nakajima K, Miyata T, Ogawa M, Mikoshiba K (1997) A novel neurological mutant mouse, yotari, which exhibits reeler-like phenotype but expresses CR-50 antigen/reelin. Neurosci Res 29(3):217–223

    Article  PubMed  CAS  Google Scholar 

  43. Buel GR, Rush J, Ballif BA (2010) Fyn promotes phosphorylation of collapsin response mediator protein 1 at tyrosine 504, a novel, isoform-specific regulatory site. J Cell Biochem 111(1):20–28

    Article  PubMed  CAS  Google Scholar 

  44. Varrin-Doyer M, Vincent P, Cavagna S, Auvergnon N, Noraz N, Rogemond V, Honnorat J, Moradi-Ameli M, Giraudon P (2009) Phosphorylation of collapsin response mediator protein 2 on Tyr-479 regulates CXCL12-induced T lymphocyte migration. J Biol Chem 284(19):13265–13276

    Article  PubMed  CAS  Google Scholar 

  45. Ohshima T, Suzuki H, Morimura T, Ogawa M, Mikoshiba K (2007) Modulation of Reelin signaling by cyclin-dependent kinase 5. Brain Res 1140:84–95

    Article  PubMed  CAS  Google Scholar 

  46. Guan KL, Rao Y (2003) Signalling mechanisms mediating neuronal responses to guidance cues. Nat Rev Neurosci 4(12):941–956

    Article  PubMed  CAS  Google Scholar 

  47. Polleux F, Giger RJ, Ginty DD, Kolodkin AL, Ghosh A (1998) Patterning of cortical efferent projections by semaphorin-neuropilin interactions. Science 282(5395):1904–1906

    Article  PubMed  CAS  Google Scholar 

  48. Raper JA (2000) Semaphorins and their receptors in vertebrates and invertebrates. Curr Opin Neurobiol 10(1):88–94

    Article  PubMed  CAS  Google Scholar 

  49. 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(1):59–69

    Article  PubMed  CAS  Google Scholar 

  50. Tamagnone L, Artigiani S, Chen H, He Z, Ming GI, Song H, Chedotal A, Winberg ML, Goodman CS, Poo M, Tessier-Lavigne M, Comoglio PM (1999) Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates. Cell 99(1):71–80

    Article  PubMed  CAS  Google Scholar 

  51. Kruger RP, Aurandt J, Guan KL (2005) Semaphorins command cells to move. Nat Rev Mol Cell Biol 6(10):789–800

    Article  PubMed  CAS  Google Scholar 

  52. Sasaki Y, Cheng C, Uchida Y, Nakajima O, Ohshima T, Yagi T, Taniguchi M, Nakayama T, Kishida R, Kudo Y, Ohno S, Nakamura F, Goshima Y (2002) Fyn and Cdk5 mediate semaphorin-3A signaling, which is involved in regulation of dendrite orientation in cerebral cortex. Neuron 35(5):907–920

    Article  PubMed  CAS  Google Scholar 

  53. Cole AR, Causeret F, Yadirgi G, Hastie CJ, McLauchlan H, McManus EJ, Hernandez F, Eickholt BJ, Nikolic M, Sutherland C (2006) Distinct priming kinases contribute to differential regulation of collapsin response mediator proteins by glycogen synthase kinase-3 in vivo. J Biol Chem 281(24):16591–16598

    Article  PubMed  CAS  Google Scholar 

  54. Brown M, Jacobs T, Eickholt B, Ferrari G, Teo M, Monfries C, Qi RZ, Leung T, Lim L, Hall C (2004) Alpha2-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(41):8994–9004

    Article  PubMed  CAS  Google Scholar 

  55. 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(6600):525–528. doi:10.1038/383525a0

    Article  PubMed  CAS  Google Scholar 

  56. 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(4):1390–1397

    PubMed  CAS  Google Scholar 

  57. 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(3):519–530

    Article  PubMed  CAS  Google Scholar 

  58. Nakamura F, Ugajin K, Yamashita N, Okada T, Uchida Y, Taniguchi M, Ohshima T, Goshima Y (2009) Increased proximal bifurcation of CA1 pyramidal apical dendrites in sema3A mutant mice. J Comp Neurol 516(5):360–375

    Article  PubMed  Google Scholar 

  59. Sytnyk V, Leshchyns'ka I, Dityatev A, Schachner M (2004) Trans-Golgi network delivery of synaptic proteins in synaptogenesis. J Cell Sci 117(Pt 3):381–388

    PubMed  CAS  Google Scholar 

  60. Morabito MA, Sheng M, Tsai LH (2004) Cyclin-dependent kinase 5 phosphorylates the N-terminal domain of the postsynaptic density protein PSD-95 in neurons. J Neurosci 24(4):865–876

    Article  PubMed  CAS  Google Scholar 

  61. Mitsui N, Inatome R, Takahashi S, Goshima Y, Yamamura H, Yanagi S (2002) Involvement of Fes/Fps tyrosine kinase in semaphorin3A signaling. Embo J 21(13):3274–3285

    Article  PubMed  CAS  Google Scholar 

  62. Lopes da Silva FH, Kamphuis W, Wadman WJ (1992) Epileptogenesis as a plastic phenomenon of the brain, a short review. Acta Neurol Scand Suppl 140:34–40

    Article  PubMed  CAS  Google Scholar 

  63. Hughes JR (1958) Post-tetanic potentiation. Physiol Rev 38(1):91–113

    PubMed  CAS  Google Scholar 

  64. Brittain JM, Piekarz AD, Wang Y, Kondo T, Cummins TR, Khanna R (2009) An atypical role for collapsin response mediator protein 2 (CRMP-2) in neurotransmitter release via interaction with presynaptic voltage-gated calcium channels. J Biol Chem 284(45):31375–31390

    Article  PubMed  CAS  Google Scholar 

  65. Chi XX, Schmutzler BS, Brittain JM, Wang Y, Hingtgen CM, Nicol GD, Khanna R (2009) Regulation of N-type voltage-gated calcium channels (Cav2.2) and transmitter release by collapsin response mediator protein-2 (CRMP-2) in sensory neurons. J Cell Sci 122(Pt 23):4351–4362

    Article  PubMed  CAS  Google Scholar 

  66. Wang Y, Brittain JM, Wilson SM, Khanna R (2010) Emerging roles of collapsin response mediator proteins (CRMPs) as regulators of voltage-gated calcium channels and synaptic transmission. Commun Integr Biol 3(2):172–175

    Article  PubMed  Google Scholar 

  67. Brittain JM, Duarte DB, Wilson SM, Zhu W, Ballard C, Johnson PL, Liu N, Xiong W, Ripsch MS, Wang Y, Fehrenbacher JC, Fitz SD, Khanna M, Park CK, Schmutzler BS, Cheon BM, Due MR, Brustovetsky T, Ashpole NM, Hudmon A, Meroueh SO, Hingtgen CM, Brustovetsky N, Ji RR, Hurley JH, Jin X, Shekhar A, Xu XM, Oxford GS, Vasko MR, White FA, Khanna R (2011) Suppression of inflammatory and neuropathic pain by uncoupling CRMP-2 from the presynaptic Ca(2+) channel complex. Nat Med 17(7):822–829

    Article  PubMed  CAS  Google Scholar 

  68. Cheung ZH, Fu AK, Ip NY (2006) Synaptic roles of Cdk5: implications in higher cognitive functions and neurodegenerative diseases. Neuron 50(1):13–18

    Article  PubMed  CAS  Google Scholar 

  69. Quinn CC, Chen E, Kinjo TG, Kelly G, Bell AW, Elliott RC, McPherson PS, Hockfield S (2003) TUC-4b, a novel TUC family variant, regulates neurite outgrowth and associates with vesicles in the growth cone. J Neurosci 23(7):2815–2823

    PubMed  CAS  Google Scholar 

  70. Arimura N, Menager C, Kawano Y, Yoshimura T, Kawabata S, Hattori A, Fukata Y, Amano M, Goshima Y, Inagaki M, Morone N, Usukura J, Kaibuchi K (2005) Phosphorylation by Rho kinase regulates CRMP-2 activity in growth cones. Mol Cell Biol 25(22):9973–9984

    Article  PubMed  CAS  Google Scholar 

  71. Nishimura T, Fukata Y, Kato K, Yamaguchi T, Matsuura Y, Kamiguchi H, Kaibuchi K (2003) CRMP-2 regulates polarized Numb-mediated endocytosis for axon growth. Nat Cell Biol 5(9):819–826

    Article  PubMed  CAS  Google Scholar 

  72. Quach TT, Duchemin AM, Rogemond V, Aguera M, Honnorat J, Belin MF, Kolattukudy PE (2004) Involvement of collapsin response mediator proteins in the neurite extension induced by neurotrophins in dorsal root ganglion neurons. Mol Cell Neurosci 25(3):433–443

    Article  PubMed  CAS  Google Scholar 

  73. Schwartz PM, Borghesani PR, Levy RL, Pomeroy SL, Segal RA (1997) Abnormal cerebellar development and foliation in BDNF−/− mice reveals a role for neurotrophins in CNS patterning. Neuron 19(2):269–281

    Article  PubMed  CAS  Google Scholar 

  74. Shimada A, Mason CA, Morrison ME (1998) TrkB signaling modulates spine density and morphology independent of dendrite structure in cultured neonatal Purkinje cells. J Neurosci 18(21):8559–8570

    PubMed  CAS  Google Scholar 

  75. Raymond LA, Blackstone CD, Huganir RL (1993) Phosphorylation of amino acid neurotransmitter receptors in synaptic plasticity. Trends Neurosci 16(4):147–153

    Article  PubMed  CAS  Google Scholar 

  76. Hirai H, Launey T (2000) The regulatory connection between the activity of granule cell NMDA receptors and dendritic differentiation of cerebellar Purkinje cells. J Neurosci 20(14):5217–5224

    PubMed  CAS  Google Scholar 

  77. Brot S, Rogemond V, Perrot V, Chounlamountri N, Auger C, Honnorat J, Moradi-Ameli M (2010) CRMP5 interacts with tubulin to inhibit neurite outgrowth, thereby modulating the function of CRMP2. J Neurosci 30(32):10639–10654

    Article  PubMed  CAS  Google Scholar 

  78. Lyness SA, Zarow C, Chui HC (2003) Neuron loss in key cholinergic and aminergic nuclei in Alzheimer disease: a meta-analysis. Neurobiol Aging 24(1):1–23

    Article  PubMed  CAS  Google Scholar 

  79. Schwartz M, Yoles E, Levin LA (1999) 'Axogenic' and 'somagenic' neurodegenerative diseases: definitions and therapeutic implications. Mol Med Today 5(11):470–473

    Article  PubMed  CAS  Google Scholar 

  80. Ross CA, Margolis RL, Reading SA, Pletnikov M, Coyle JT (2006) Neurobiology of schizophrenia. Neuron 52(1):139–153

    Article  PubMed  CAS  Google Scholar 

  81. Yoshida H, Watanabe A, Ihara Y (1998) Collapsin response mediator protein-2 is associated with neurofibrillary tangles in Alzheimer's disease. J Biol Chem 273(16):9761–9768

    Article  PubMed  CAS  Google Scholar 

  82. Gu Y, Hamajima N, Ihara Y (2000) Neurofibrillary tangle-associated collapsin response mediator protein-2 (CRMP-2) is highly phosphorylated on Thr-509, Ser-518, and Ser-522. Biochemistry 39(15):4267–4275

    Article  PubMed  CAS  Google Scholar 

  83. Cole AR, Noble W, van Aalten L, Plattner F, Meimaridou R, Hogan D, Taylor M, LaFrancois J, Gunn-Moore F, Verkhratsky A, Oddo S, LaFerla F, Giese KP, Dineley KT, Duff K, Richardson JC, Yan SD, Hanger DP, Allan SM, Sutherland C (2007) Collapsin response mediator protein-2 hyperphosphorylation is an early event in Alzheimer's disease progression. J Neurochem 103(3):1132–1144

    Article  PubMed  CAS  Google Scholar 

  84. Kawas CH, Corrada MM, Brookmeyer R, Morrison A, Resnick SM, Zonderman AB, Arenberg D (2003) Visual memory predicts Alzheimer's disease more than a decade before diagnosis. Neurology 60(7):1089–1093

    PubMed  CAS  Google Scholar 

  85. Cruz JC, Tseng HC, Goldman JA, Shih H, Tsai LH (2003) Aberrant Cdk5 activation by p25 triggers pathological events leading to neurodegeneration and neurofibrillary tangles. Neuron 40(3):471–483

    Article  PubMed  CAS  Google Scholar 

  86. Patrick GN, Zukerberg L, Nikolic M, de la Monte S, Dikkes P, Tsai LH (1999) Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration. Nature 402(6762):615–622

    Article  PubMed  CAS  Google Scholar 

  87. Tseng HC, Zhou Y, Shen Y, Tsai LH (2002) A survey of Cdk5 activator p35 and p25 levels in Alzheimer's disease brains. FEBS Lett 523(1–3):58–62

    Article  PubMed  CAS  Google Scholar 

  88. Good PF, Alapat D, Hsu A, Chu C, Perl D, Wen X, Burstein DE, Kohtz DS (2004) A role for semaphorin 3A signaling in the degeneration of hippocampal neurons during Alzheimer's disease. J Neurochem 91(3):716–736

    Article  PubMed  CAS  Google Scholar 

  89. Beasley CL, Pennington K, Behan A, Wait R, Dunn MJ, Cotter D (2006) Proteomic analysis of the anterior cingulate cortex in the major psychiatric disorders: evidence for disease-associated changes. Proteomics 6(11):3414–3425

    Article  PubMed  CAS  Google Scholar 

  90. Edgar PF, Douglas JE, Cooper GJ, Dean B, Kydd R, Faull RL (2000) Comparative proteome analysis of the hippocampus implicates chromosome 6q in schizophrenia. Mol Psychiatry 5(1):85–90

    Article  PubMed  CAS  Google Scholar 

  91. Hong LE, Wonodi I, Avila MT, Buchanan RW, McMahon RP, Mitchell BD, Stine OC, Carpenter WT Jr, Thaker GK (2005) Dihydropyrimidinase-related protein 2 (DRP-2) gene and association to deficit and nondeficit schizophrenia. Am J Med Genet B Neuropsychiatr Genet 136B(1):8–11

    Article  PubMed  Google Scholar 

  92. Johnston-Wilson NL, Sims CD, Hofmann JP, Anderson L, Shore AD, Torrey EF, Yolken RH (2000) Disease-specific alterations in frontal cortex brain proteins in schizophrenia, bipolar disorder, and major depressive disorder. The Stanley Neuropathology Consortium. Mol Psychiatry 5(2):142–149

    Article  PubMed  CAS  Google Scholar 

  93. Ujike H, Sakai A, Nakata K, Tanaka Y, Kodaka T, Okahisa Y, Harano M, Inada T, Yamada M, Komiyama T, Hori T, Sekine Y, Iwata N, Sora I, Iyo M, Ozaki N, Kuroda S (2006) Association study of the dihydropyrimidinase-related protein 2 gene and methamphetamine psychosis. Ann N Y Acad Sci 1074:90–96

    Article  PubMed  CAS  Google Scholar 

  94. Braff DL, Geyer MA (1990) Sensorimotor gating and schizophrenia. Human and animal model studies. Arch Gen Psychiatry 47(2):181–188

    Article  PubMed  CAS  Google Scholar 

  95. Quach TT, Glasper ER, Devries AC, Honnorat J, Kolattukudy PE, Duchemin AM (2008) Altered prepulse inhibition in mice with dendrite abnormalities of hippocampal neurons. Mol Psychiatry 13(7):656–658

    Article  PubMed  CAS  Google Scholar 

  96. Wang LH, Strittmatter SM (1997) Brain CRMP forms heterotetramers similar to liver dihydropyrimidinase. J Neurochem 69(6):2261–2269

    Article  PubMed  CAS  Google Scholar 

  97. Bretin S, Reibel S, Charrier E, Maus-Moatti M, Auvergnon N, Thevenoux A, Glowinski J, Rogemond V, Premont J, Honnorat J, Gauchy C (2005) Differential expression of CRMP1, CRMP2A, CRMP2B, and CRMP5 in axons or dendrites of distinct neurons in the mouse brain. J Comp Neurol 486(1):1–17

    Article  PubMed  CAS  Google Scholar 

  98. Assadi AH, Zhang G, Beffert U, McNeil RS, Renfro AL, Niu S, Quattrocchi CC, Antalffy BA, Sheldon M, Armstrong DD, Wynshaw-Boris A, Herz J, D'Arcangelo G, Clark GD (2003) Interaction of reelin signaling and Lis1 in brain development. Nat Genet 35(3):270–276

    Article  PubMed  CAS  Google Scholar 

  99. Ballif BA, Arnaud L, Arthur WT, Guris D, Imamoto A, Cooper JA (2004) Activation of a Dab1/CrkL/C3G/Rap1 pathway in Reelin-stimulated neurons. Curr Biol 14(7):606–610

    Article  PubMed  CAS  Google Scholar 

  100. Suetsugu S, Tezuka T, Morimura T, Hattori M, Mikoshiba K, Yamamoto T, Takenawa T (2004) Regulation of actin cytoskeleton by mDab1 through N-WASP and ubiquitination of mDab1. Biochem J 384(Pt 1):1–8

    PubMed  CAS  Google Scholar 

  101. Sato Y, Taoka M, Sugiyama N, Kubo K, Fuchigami T, Asada A, Saito T, Nakajima K, Isobe T, Hisanaga S (2007) Regulation of the interaction of disabled-1 with CIN85 by phosphorylation with cyclin-dependent kinase 5. Genes Cells 12(12):1315–1327

    Article  PubMed  CAS  Google Scholar 

  102. Kurnellas MP, Li H, Jain MR, Giraud SN, Nicot AB, Ratnayake A, Heary RF, Elkabes S (2010) Reduced expression of plasma membrane calcium ATPase 2 and collapsin response mediator protein 1 promotes death of spinal cord neurons. Cell Death Differ 17(9):1501–1510

    Article  PubMed  CAS  Google Scholar 

  103. Arimura N, Inagaki N, Chihara K, Menager C, Nakamura N, Amano M, Iwamatsu A, Goshima Y, Kaibuchi K (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(31):23973–23980

    Article  PubMed  CAS  Google Scholar 

  104. Ito Y, Oinuma I, Katoh H, Kaibuchi K, Negishi M (2006) Sema4D/plexin-B1 activates GSK-3beta through R-Ras GAP activity, inducing growth cone collapse. EMBO Rep 7(7):704–709

    Article  PubMed  CAS  Google Scholar 

  105. Mimura F, Yamagishi S, Arimura N, Fujitani M, Kubo T, Kaibuchi K, Yamashita T (2006) Myelin-associated glycoprotein inhibits microtubule assembly by a Rho-kinase-dependent mechanism. J Biol Chem 281(23):15970–15979

    Article  PubMed  CAS  Google Scholar 

  106. Morinaka A, Yamada M, Itofusa R, Funato Y, Yoshimura Y, Nakamura F, Yoshimura T, Kaibuchi K, Goshima Y, Hoshino M, Kamiguchi H, Miki H (2011) Thioredoxin mediates oxidation-dependent phosphorylation of CRMP2 and growth cone collapse. Sci Signal 4(170):ra26

    Article  PubMed  CAS  Google Scholar 

  107. Inagaki N, Chihara K, Arimura N, Menager C, Kawano Y, Matsuo N, Nishimura T, Amano M, Kaibuchi K (2001) CRMP-2 induces axons in cultured hippocampal neurons. Nat Neurosci 4(8):781–782

    Article  PubMed  CAS  Google Scholar 

  108. Kawano Y, Yoshimura T, Tsuboi D, Kawabata S, Kaneko-Kawano T, Shirataki H, Takenawa T, Kaibuchi K (2005) CRMP-2 is involved in kinesin-1-dependent transport of the Sra-1/WAVE1 complex and axon formation. Mol Cell Biol 25(22):9920–9935

    Article  PubMed  CAS  Google Scholar 

  109. Zhu LQ, Zheng HY, Peng CX, Liu D, Li HL, Wang Q, Wang JZ (2010) Protein phosphatase 2A facilitates axonogenesis by dephosphorylating CRMP2. J Neurosci 30(10):3839–3848

    Article  PubMed  CAS  Google Scholar 

  110. Suzuki Y, Nakagomi S, Namikawa K, Kiryu-Seo S, Inagaki N, Kaibuchi K, Aizawa H, Kikuchi K, Kiyama H (2003) Collapsin response mediator protein-2 accelerates axon regeneration of nerve-injured motor neurons of rat. J Neurochem 86(4):1042–1050

    Article  PubMed  CAS  Google Scholar 

  111. Bretin S, Rogemond V, Marin P, Maus M, Torrens Y, Honnorat J, Glowinski J, Premont J, Gauchy C (2006) Calpain product of WT-CRMP2 reduces the amount of surface NR2B NMDA receptor subunit. J Neurochem 98(4):1252–1265

    Article  PubMed  CAS  Google Scholar 

  112. Hou ST, Jiang SX, Aylsworth A, Ferguson G, Slinn J, Hu H, Leung T, Kappler J, Kaibuchi K (2009) CaMKII phosphorylates collapsin response mediator protein 2 and modulates axonal damage during glutamate excitotoxicity. J Neurochem 111(3):870–881

    Article  PubMed  CAS  Google Scholar 

  113. Aylsworth A, Jiang SX, Desbois A, Hou ST (2009) Characterization of the role of full-length CRMP3 and its calpain-cleaved product in inhibiting microtubule polymerization and neurite outgrowth. Exp Cell Res 315(16):2856–2868

    Article  PubMed  CAS  Google Scholar 

  114. Hou ST, Jiang SX, Desbois A, Huang D, Kelly J, Tessier L, Karchewski L, Kappler J (2006) Calpain-cleaved collapsin response mediator protein-3 induces neuronal death after glutamate toxicity and cerebral ischemia. J Neurosci 26(8):2241–2249

    Article  PubMed  CAS  Google Scholar 

  115. Liu W, Zhou XW, Liu S, Hu K, Wang C, He Q, Li M (2009) Calpain-truncated CRMP-3 and -4 contribute to potassium deprivation-induced apoptosis of cerebellar granule neurons. Proteomics 9(14):3712–3728

    Article  PubMed  CAS  Google Scholar 

  116. Alabed YZ, Pool M, Ong Tone S, Fournier AE (2007) Identification of CRMP4 as a convergent regulator of axon outgrowth inhibition. J Neurosci 27(7):1702–1711

    Article  PubMed  CAS  Google Scholar 

  117. Alabed YZ, Pool M, Ong Tone S, Sutherland C, Fournier AE (2010) GSK3 beta regulates myelin-dependent axon outgrowth inhibition through CRMP4. J Neurosci 30(16):5635–5643

    Article  PubMed  CAS  Google Scholar 

  118. Duplan L, Bernard N, Casseron W, Dudley K, Thouvenot E, Honnorat J, Rogemond V, De Bovis B, Aebischer P, Marin P, Raoul C, Henderson CE, Pettmann B (2010) Collapsin response mediator protein 4a (CRMP4a) is upregulated in motoneurons of mutant SOD1 mice and can trigger motoneuron axonal degeneration and cell death. J Neurosci 30(2):785–796

    Article  PubMed  CAS  Google Scholar 

  119. Hotta A, Inatome R, Yuasa-Kawada J, Qin Q, Yamamura H, Yanagi S (2005) Critical role of collapsin response mediator protein-associated molecule CRAM for filopodia and growth cone development in neurons. Mol Biol Cell 16(1):32–39

    Article  PubMed  CAS  Google Scholar 

  120. Yamashita N, Nakamura F, Goshima Y (2009) Role of Cdk5 in axon guidance and synapse development. Tanpakushitsu Kakusan Koso 54(7):802–807

    PubMed  CAS  Google Scholar 

  121. Cole AR, Knebel A, Morrice NA, Robertson LA, Irving AJ, Connolly CN, Sutherland C (2004) GSK-3 phosphorylation of the Alzheimer epitope within collapsin response mediator proteins regulates axon elongation in primary neurons. J Biol Chem 279(48):50176–50180

    Article  PubMed  CAS  Google Scholar 

  122. Arimura N, Kimura T, Nakamuta S, Taya S, Funahashi Y, Hattori A, Shimada A, Menager C, Kawabata S, Fujii K, Iwamatsu A, Segal RA, Fukuda M, Kaibuchi K (2009) Anterograde transport of TrkB in axons is mediated by direct interaction with Slp1 and Rab27. Dev Cell 16(5):675–686

    Article  PubMed  CAS  Google Scholar 

  123. Boudreau AC, Ferrario CR, Glucksman MJ, Wolf ME (2009) Signaling pathway adaptations and novel protein kinase A substrates related to behavioral sensitization to cocaine. J Neurochem 110(1):363–377

    Article  PubMed  CAS  Google Scholar 

  124. Ong Tone S, Dayanandan B, Fournier AE, Mandato CA (2010) GSK3 regulates mitotic chromosomal alignment through CRMP4. PLoS One 5(12):e14345

    Article  PubMed  CAS  Google Scholar 

  125. Marrs GS, Green SH, Dailey ME (2001) Rapid formation and remodeling of postsynaptic densities in developing dendrites. Nat Neurosci 4(10):1006–1013

    Article  PubMed  CAS  Google Scholar 

  126. Ahmari SE, Buchanan J, Smith SJ (2000) Assembly of presynaptic active zones from cytoplasmic transport packets. Nat Neurosci 3(5):445–451

    Article  PubMed  CAS  Google Scholar 

  127. Friedman HV, Bresler T, Garner CC, Ziv NE (2000) Assembly of new individual excitatory synapses: time course and temporal order of synaptic molecule recruitment. Neuron 27(1):57–69

    Article  PubMed  CAS  Google Scholar 

  128. Okabe S, Miwa A, Okado H (2001) Spine formation and correlated assembly of presynaptic and postsynaptic molecules. J Neurosci 21(16):6105–6114

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Dr. Toshio Ohshima and all the members of the Department of Molecular Pharmacology and Neurobiology at Yokohama City University. We also thank Dr. Pappachan Kolattukudy, Dr. Jérôme Honnorat, Dr. Nicole Thomasset, and Dr. Masahiko Taniguchi for providing mutant mice and helpful discussion. This work was supported by CREST of JST (Y.G.), grants-in-aid for Scientific Research in a Priority Area from the Ministry of Education, Science, Sports and Culture (Y.G.), JSPS Research Fellowships for Young Scientists (N.Y.), JSPS 21st century COE program (N.Y. and Y.G), and the Yokohama Medical Foundation (N.Y., Y.G.).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yoshio Goshima.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yamashita, N., Goshima, Y. Collapsin Response Mediator Proteins Regulate Neuronal Development and Plasticity by Switching Their Phosphorylation Status. Mol Neurobiol 45, 234–246 (2012). https://doi.org/10.1007/s12035-012-8242-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-012-8242-4

Keywords

Navigation