Skip to main content
SpringerLink
Log in

Transduction of Inhibitory Signals by the Axonal Growth Cone

  • Chapter
Neurobiology of Spinal Cord Injury

Part of the book series: Contemporary Neuroscience ((CNEURO))

  • 230 Accesses

Abstract

The distal tip of the growing axons is a specialized structure termed the growth cone, consisting of a lamelipodium with numerous filopodial extensions (1,2) (Fig. 1). The growth cone is largely responsible for determining the direction as well as the extent of axon outgrowth. Obviously, axonal growth cone function is critical for neuronal development and hence the proper functioning of the adult nervous system. The same mechanisms are thought to determine whether adult axons regenerate (as in peripheral nerve injury) or fail to regenerate (as in spinal cord injury). When regeneration does occur, adult axons are thought to utilize the same guidance cues that developing axons use to identify appropriate synaptic partners among a myriad of possibilities. In this review, the molecular cues known to inhibit axonal outgrowth are briefly reviewed and the mechanisms of their action on growth cones considered in detail.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ramón y Cajal, S. (1890) A quelle époque apparaissent les expansions des cellules nerveuses de la moelle epinère du poulet. Anat. Anzerger 5, 609–613.

    Google Scholar 

  2. Strittmatter, S. M. (1995) Neuronal guidance molecules: inhibitory and soluble factors. Neuroscientist 1, 255–258.

    Article  CAS  Google Scholar 

  3. Snider, W. D. (1994) Functions of the neurotrophins during nervous system development: what the knockouts are teaching us. Cell 77, 627–638.

    Article  PubMed  Google Scholar 

  4. Dodd, J. and Jessell, T. M. (1988) Axon guidance and the patterning of neuronal projections in vertebrates. Science 242, 692–699.

    Article  PubMed  CAS  Google Scholar 

  5. Jouet, M., Rosenthal, A., Armstrong, G., et al. (1994) X-linked spastic paraplegia (SPG1), MASA syndrome and X-linked hydrocephalus result from mutations in the L1 gene. Nature Genet. 7, 402–407.

    Article  PubMed  CAS  Google Scholar 

  6. Cohen, N. R., Taylor, J. S. H., Scott, L. B., et al. (1997) Errors in corticospinal axon guidance in mice lacking the neural cell adhesion molecule L1. Curr. Biol. 8, 26–33.

    Article  Google Scholar 

  7. Reichardt, L. E. and Tomaselli, K. J. (1991) Extracellular matrix molecules and their receptors: functions in neural development. Annu. Rev. Neurosci. 14, 531–570.

    Article  PubMed  CAS  Google Scholar 

  8. Serafini, T., Kennedy, T. E., Falko, N. J., et al. (1994) The netrins define a family of axon outgrowth-promoting proteins homologous to C. elegans UNC-6. Cell 78, 409–424.

    Article  PubMed  CAS  Google Scholar 

  9. Chan, S. S.-Y., Zheng, H., Su, M.-W., et al. (1996) UNC-40 a C. elegans homolog of DCC (deleted in colorectal cancer) is required in motile cells responding to UNC-6 netrin cues. Cell 87, 187–195.

    Article  PubMed  CAS  Google Scholar 

  10. Keino-Masu, K., Masu, H., Hinck, L., et al. (1996) Deleted in colorectal cancer (DCC) encodes a netrin receptor. Cell 87, 175–185.

    Article  PubMed  CAS  Google Scholar 

  11. Kidd, T., Brose, K., Mitchell, K. J., et al. (1998) Roundabout controls axon crossing of the CNS midline and defines a novel subfamily of evolutionarily conserved guidance receptors. Cell 92, 205–215.

    Article  PubMed  CAS  Google Scholar 

  12. Kidd, T., Russell, C., Goodman, C. S., and Tear, G. (1998) Dosage-sensitive and complementary functions of roundabout and commissureless control axon crossing of the CNS midline. Neuron 20, 25–33.

    Article  PubMed  CAS  Google Scholar 

  13. Raper, J. A. and Kapfhammer, J. P. (1990) The enrichment of a neuronal growth cone collapsing activity from embryonic chick brain. Neuron 2, 21–29.

    Article  Google Scholar 

  14. Walter, J., Kern-Veits, B., Huf, J., Stolze, B., and Bonhoeffer, F. (1987) Recognition of position-specific properties of tectal cell membranes by retinal axons in vitro. Development 101, 685–696.

    PubMed  CAS  Google Scholar 

  15. Luo, Y., Raible, D., and Raper, J. A. (1993) Collapsin: a protein in brain that induces the collapse and paralysis of neuronal growth cones. Cell 75, 217–227.

    Article  PubMed  CAS  Google Scholar 

  16. Kolodkin, A. L., Matthews, D. J., O’Connor, T. P., et al. (1992) Fasciclin IV: sequence, expression, and function during growth cone guidance in the grasshopper embryo. Neuron 9, 831–845.

    Article  PubMed  CAS  Google Scholar 

  17. Kolodkin, A. L., Matthews, D. J., and Goodman, C. S. (1993) The semaphorin genes encodes a family of transmembrane and secreted growth cone guidance molecules. Cell 75, 1389–1399.

    Article  PubMed  CAS  Google Scholar 

  18. Kolodkin, A. (1996) Semaphorins: mediators of repulsive growth cone guidance. Trends Cell Biol. 6, 15–22.

    Article  PubMed  CAS  Google Scholar 

  19. Püschel, A. W. (1996) The semaphorins: a family of axonal guidance molecules? Eur. J. Neurosci. 8, 1317–1321.

    Article  PubMed  Google Scholar 

  20. Taniguchi, M., Yuasa, S., Fujisawa, H., et al. (1997) Disruption of semaphorin III/D gene causes severe abnormality in peripheral nerve projection. Neuron 19, 519–530.

    Article  PubMed  CAS  Google Scholar 

  21. Messersmith, E. K., Leonardo, E. D., Shatz, C. J., et al. (1995) Semaphorin III can function as a selective chemorepellent to pattern sensory projections in the spinal cord. Neuron 14, 949–959.

    Article  PubMed  CAS  Google Scholar 

  22. Püschel, A. W., Adams, R. H., and Betz, H. (1995) Murine semaphorin D/collapsin is a member of a diverse gene family and creates domains inhibitory for axonal extension. Neuron 14, 941–948.

    Article  PubMed  Google Scholar 

  23. Behar, O., Golden, J. A., Mashimo, H., Schoen, E J., and Fishman, M. C. (1996) Semaphorin III is needed for normal patterning and growth of nerves, bones, and heart. Nature 383, 525–528.

    Article  PubMed  CAS  Google Scholar 

  24. Matthes, D. J., Sink, H., Kolodkin, A. L., and Goodman, C. S. (1995) Semaphorin II can function as a selective inhibitor of specific synaptic arborization. Cell 81, 631–639.

    Article  PubMed  CAS  Google Scholar 

  25. Winberg, M. L., Mitchel, K. J., and Goodman, C. S. (1998) Genetic analysis of the mechanisms controlling target selection:complementary and combinatorial functions of netrins, semaphorins, and IgCAMs. Cell 93, 581–591.

    Article  PubMed  CAS  Google Scholar 

  26. Yu, H.-H., Araj, H. H., Ralls, S. A., and Kolodkin, A. L. (1998) The transmembrane semaphorin sema I is required in Drosophila for embryonic motor and CNS axon guidance. Neuron 20, 207–220.

    Article  PubMed  CAS  Google Scholar 

  27. Shepherd, I., Luo, Y., Raper, J. A., and Chang, S. (1996) The distribution of collapsin-1 mRNA in the developing chick nervous system. Dey. Biol. 173, 185–199

    Article  CAS  Google Scholar 

  28. Giger, R. J., Wolfer, D. P., De Wit, G. M. J., et al. (1996) Anatomy of rat semaphorinllUcollapsin-1 mRNA expression and relationship to developing nerve tracts during neuroembryogenesis. J. Comp. Neurol. 375, 378–392.

    Article  PubMed  CAS  Google Scholar 

  29. Polleux, F., Giger, R. J., Ginty, D. D., Kolodkin, A. L., and Ghosh, A. (1998) Patterning of cortical efferent projections by semaphorin-neuropilin interactions. Science 282, 1904–1906.

    Article  PubMed  CAS  Google Scholar 

  30. Furuyama, T., Inagaki, S., Kosugi, A., et al. (1996) Identification of a novel trans-membrane semaphorin expressed on lymphocytes. J. Biol. Chem. 271, 33376–33381.

    Article  PubMed  CAS  Google Scholar 

  31. Hall, K. T., Boumsell, L., Schultze, J., et al. (1996) Human CD100, a novel leukocyte semaphorin that promotes B-cell aggregation and differentiation. Proc. Natl. Acad. Sci. USA 93, 11780–11785.

    Article  PubMed  CAS  Google Scholar 

  32. Comeau, M. R., Johnson, R., DuBose, R. F., et al. (1998) A poxvirus-encoded semaphorin induces cytokine production from monocytes and binds to a novel cellular semaphorin receptor, VESPR. Immunity 8, 473–482.

    Article  PubMed  CAS  Google Scholar 

  33. Sekido, Y., Bader, S., Latif, F., et al. (1996) Human semaphorin A(V) and IV reside in the 3p21.3 small cell lung cancer deletion region and demonstrate distinct expression patterns. Proc. Natl. Acad. Sci. USA 93, 4120–4125.

    Article  PubMed  CAS  Google Scholar 

  34. Flanagan, J. G. and Vanderhaeghen, P. (1998) The ephrins and Eph receptors in neural development. Annu. Rev. Neurosci. 21, 309–345.

    Article  PubMed  CAS  Google Scholar 

  35. Bonhoeffer, F. and Huf, J. (1982) In vitro experiments on axon guidance demonstrationg an anterior-posterior gradient on the tectum. EMBO J. 4, 427–431.

    Google Scholar 

  36. Walter, J. Henke-Fahle, S., and Bonhoeffer, F. (1987) Avoidance of posterior tectal membranes by temporal retinal axons. Development 101, 909–913.

    PubMed  CAS  Google Scholar 

  37. Drescher, U., Kremoser, C., Handwrecker, C., et al. (1995) In vitro guidance of retinal ganglion cell axons by RAGS, a 25 kDa tectal protein related to ligands for Eph receptor tyrosine kinases. Cell 82, 359–370.

    Article  PubMed  CAS  Google Scholar 

  38. Cheng, H.-J., Nakamoto, M., Bergemann, A. D., and Flanagan, J. G. (1995) Complementary gradients in expression and binding of ELF-1 and Mek4 in development of the topographic retintectal projection map. Cell 82, 371–381.

    Article  PubMed  CAS  Google Scholar 

  39. Nakamoto, M., Cheng, H.-J., Friedman, G. C., et al. (1996) Topographically specific effects of ELF-1 on retinal axon guidance in vitro and retinal axon mapping in vivo. Cell 86, 755–766.

    Article  PubMed  CAS  Google Scholar 

  40. Frisen, J., Yates, P. A., McLaughlin, T., et al. (1998) Ephrin-A5 (AL-1/RAGS) is essential for proper retinal axon guidance and topographic mapping in the mammalian visual system. Neuron 20, 235–243.

    Article  PubMed  CAS  Google Scholar 

  41. Henkemeyer, M., Orioli, D., Henderson, J. T., et al. (1996) Nuk controls pathfinding of commissural axons in the mammalian central nervous system. Cell 86, 35–46.

    Article  PubMed  CAS  Google Scholar 

  42. Kennedy, T. E., Serafini, T., de la Torre, J. R., and Tessier-Lavigne, M. (1994) Netrins are diffusible chemotropic factors for commissural axons in the embryonic spinal cord. Cell 78, 425–435.

    Article  PubMed  CAS  Google Scholar 

  43. Colamarino, S. A. and Tessier-Lavigne, M. (1995) The axonal chemoattractant netrin-1 is also a chemorepellent for trochlear motor axons. Cell 81, 621–629.

    Article  PubMed  CAS  Google Scholar 

  44. Hedgecock, E. M., Culotti, J. G., and Hall, D. H. (1990) The unc-5, unc-6 and unc40 genes guide circumferential migrations of pioneer axons and mesodermal cells on the epidermis in C. elegans. Neuron 4, 61–85.

    Article  CAS  Google Scholar 

  45. Ishii, N., Wadsworth, W. G., Stern, B. D., Culotti, J. G., and Hedgecock, E. M. (1992) UNC-6, a laminin-related protein, guides cells and pioneer axon migrations in C. elegans. Neuron 9, 873–881.

    Article  CAS  Google Scholar 

  46. Kolodziej, P. A., et al. (1996) Frazzled encodes a Drosophila member of the DCC immunoglobulin subfamily and is required for CNS and motor axon guidance. Cell 87, 197–204.

    Article  PubMed  CAS  Google Scholar 

  47. Hamelin, M., Zhou, Y., Su, M.-W., Scott, I. M., and Culotti, J. G. (1993) Expression of the unc-5 guidance gene in the touch neurons of C. elegans steers their axons dorsally. Nature 364, 327–330.

    Article  PubMed  CAS  Google Scholar 

  48. David, S. and Aguayo, A. J. (1981) Axonal elongation in peripheral nervous system bridges after central nervous system injury in adult rats. Science 214, 391–393.

    Article  Google Scholar 

  49. Vidal-Sanz, M., Bray, G. M., Villegas-Perez, M. P., Thanos, S., and Aguayo, A. J. (1987) Axonal regeneration and synapse formation in the superior colliculus by retinal ganglion cells in the adult retina. J. Neurosci. 7, 2894–2909.

    PubMed  CAS  Google Scholar 

  50. Schwab, M. E. and Thoenen, H. (1985) Dissociated neurons regenerate into sciatic but not optic nerve explants in culture irrespective of neurotrophic factors. J. Neurosci. 5, 2415–2423.

    PubMed  CAS  Google Scholar 

  51. Caroni, P. and Schwab, M. E. (1988) Two membrane protein fractions from rat central myelin with inhibitory properties for neurite growth and fibroblast spreading. J. Cell Biol. 106, 1281–1288.

    Article  PubMed  CAS  Google Scholar 

  52. Caroni, P. and Schwab, M. E. (1988) Antibody against myelin-associated inhibitor of neurite growth neutralizes nonpermissive substrate properties of CNS white matter. Neuron 1, 85–96.

    Article  PubMed  CAS  Google Scholar 

  53. Schnell, L. and Schwab, M. E. (1990) Axonal regeneration in the rat spinal cord produced by an antibody against myelin-associated neurite growth inhibitors. Nature 343, 269–272.

    Article  PubMed  CAS  Google Scholar 

  54. Spillmann, A. A., Bandtlow, C. E., Lottspeich, F., Keller, F., and Schwab, M. E. (1998) Identification and characterization of a bovine neurite growth inhibitor (bNI220). J. Biol. Chem. 273, 19283–19293.

    Article  PubMed  CAS  Google Scholar 

  55. McKerracher, L., David, S., Jackson, D. L., et al. (1994) Identification of myelin-associated glycoprotein as a major myelin-derived inhibitor of neurite growth. Neuron 13, 805–811.

    Article  PubMed  CAS  Google Scholar 

  56. Mukhopadhyay, G., Doherty, P., Walsh, F. S., Crocker, R., and Filbin, M. T. (1994) A novel role for myelin-associated glycoprotein as an inhibitor of axonal regeneration. Neuron 13, 805–811.

    Article  Google Scholar 

  57. Bartsch, S., Montag, D., Schachner, M., and Bartsch, U. (1997) Increased number of unmyelinated axons in optic nerves of adult mice deficient in the myelin-associated glycoprotein (MAG). Brain Res. 11, 231–234.

    Article  Google Scholar 

  58. Schwab, M. E., Kapfhammer, J. P., and Bandtlow, C. E. (1993) Inhibitors of neurite outgrowth. Annu. Rev. Neurosci. 16, 565–595.

    Article  PubMed  CAS  Google Scholar 

  59. Benowitz, L. I. and Rottenberg, A. (1987) A membrane phosphoprotein associated with neural development, axonal regeneration, phospholipid metabolism, and sysnaptic plasticity. Trends Neurosci. 10, 527–532.

    Article  CAS  Google Scholar 

  60. Skene, J. H. P. (1989) Axonal growth-associated proteins. Annu. Rev. Neurosci. 12, 127–156.

    Article  PubMed  CAS  Google Scholar 

  61. Pasterkamp, R. J., Giger, R. J., and Verhaagen, J. (1998) Regulation of semaphorin IIUcollapsin-1 gene expression during peripheral nerve regeneration. Exp. Neurol. 153, 313–327.

    Article  PubMed  CAS  Google Scholar 

  62. Skene, J. H. P., Jacobson, R. D., Snipes, G. J., et al. (1986) A protein induced during nerve growth (GAP-43) is a major component of growth-cone membranes. Science 233, 783–785.

    Article  PubMed  CAS  Google Scholar 

  63. Zuber, M., Strittmatter, S. M., and Fishman, M. C. (1989) A membrane-targeting signal in the amino terminus of the neuronal protein GAP-43. Nature 341, 345–348.

    Article  PubMed  CAS  Google Scholar 

  64. Strittmatter, S. M., Fankhauser, C., Huang, P. L., Mashimo, H., and Fishman, M. C. (1995) Neuronal pathfinding is abnormal in mice lacking the neuronal growth cone protein GAP-43. Cell 80, 445–452.

    Article  PubMed  CAS  Google Scholar 

  65. Aigner, L., Arber, S., Kapfhammer, J. P., et al. (1995) Overexpression of the neural growth-associated protein GAP-43 induces nerve sprouting in the adult nervous system of transgenic mice. Cell 83, 269–278.

    Article  PubMed  CAS  Google Scholar 

  66. Strittmatter, S. M., Valenzuela, D., Kennedy, T. E., and Fishman, M C (1990) Go is a major growth cone protein subject to regulation by GAP-43. Nature 344, 836–841.

    Article  PubMed  CAS  Google Scholar 

  67. Strittmatter, S. M., Cannon, S. C., Ross, E. M., Higashijima, T., and Fishman, M. C. (1993) GAP-43 augments G protein-coupled receptor transduction in Xenopus laevis oocytes. Proc. Natl. Acad. Sci. USA 90, 5327–5331.

    Article  PubMed  CAS  Google Scholar 

  68. Alexander, K. A., Cimier, B. M., Meier, K. E., and Storm, D. R. (1987) Regulation of calmodulin binding to P-57. A neurospecific calmodulin binding protein. J. Biol. Chem. 262, 6108–6113.

    PubMed  CAS  Google Scholar 

  69. Nakamura, F., Strittmatter, P., and Strittmatter, S. M. (1998) GAP-43 augmentation of G protein-mediated signal transduction is required by both phosphorylation and palmitoylation. J. Neurochem. 70, 983–992.

    Article  PubMed  CAS  Google Scholar 

  70. Pfenninger, K. H., Ellis, L., Johnson, M. P., Friedman, L. B., and Somlo, S. (1983) Nerve growth cones isolated from fetal rat brain. Subcellular fractionation and characterization. Cell 35, 573–584.

    Article  PubMed  CAS  Google Scholar 

  71. Strittmatter, S. M., Fishman, M. C., and Zhu, X. P. (1994) Activated mutants of the alpha subunit of G(o) promote an increased number of neuntes per cell. J. Neurosci. 14, 2327–2338.

    PubMed  CAS  Google Scholar 

  72. Jiang, M., Gold, M. S., Boulay, G., et al. (1998) Multiple neurological abnormalities in mice deficient in the G protein Go. Proc. Natl. Acad. Sci. USA 95, 3269–3274.

    Article  PubMed  CAS  Google Scholar 

  73. Valenzuela, D., Han, X., Mende, U., et al. (1997) G alpha(o) is necessary for muscarinic regulation of Cat+ channel in mouse heart. Proc. Natl. Acad. Sci. USA 94, 1727–1732.

    Article  PubMed  CAS  Google Scholar 

  74. Haydon, P. G., McCobb, D. P., and Kater, S. B. (1984) Serotonin selectively inhibits growth cone motility and synaptogenesis of specific identified neuron. Science 226, 561–564.

    Article  PubMed  CAS  Google Scholar 

  75. Rodrigues, P. S. and Dowling, J. E. (1990) Dopamine induces neurite retraction in retinal horizontal cells via diacylglycerol and protein kinase C. Proc. Natl. Acad. Sci. USA 87, 9693–9697.

    Article  Google Scholar 

  76. Jalink, K., Corven, E. J., Hengeveld, T., et al. (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.

    Article  PubMed  CAS  Google Scholar 

  77. Clapham, D. E. (1995) Calcium signaling. Cell 80, 259–269.

    Article  PubMed  CAS  Google Scholar 

  78. Kuhn, T. B., Schmidt, M. F., and Kater, S. B. (1995) Laminin and fibronectin guideposts signal sustained by opposite effects to passing growth cones. Neuron 14, 275–285.

    Article  PubMed  CAS  Google Scholar 

  79. Kuhn, T. B., Williams, C. V., Dou, P., and Kater, S. B. (1998) Laminin directs growth cone navigation via two temporally and functionally distinct calcium signals. J. Neurosci. 18, 184–194.

    PubMed  CAS  Google Scholar 

  80. Silver, R. A., Lamb, A. G., and Bolsover, S. R. (1990) Calcium hotspots caused by L-channel clustering promote morphological changes in neuronal growth cones. Nature 343, 751–754.

    Article  PubMed  CAS  Google Scholar 

  81. Doherty, P. and Walsh, F. S. (1994) Signal transduction events underlying neurite outgrowth stimulated by cell adhesion molecules. Curr. Opin. Neurobiol. 4, 49–55.

    Article  PubMed  CAS  Google Scholar 

  82. Takei, K., Shin, R.-M., Inoue, T., Kato, K., and Mikoshiba, K. (1998) Regulation of nerve growth mediated by inositol 1,4,5-trisphosphate receptors in growth cones. Science 282, 1705–1708.

    Article  PubMed  CAS  Google Scholar 

  83. Ming, G.-L., Song, H. J., Berringer, B., et al. (1997) cAMP-dependent growth cone guidance by netrin-1. Neuron 19, 1225–1235.

    Article  PubMed  CAS  Google Scholar 

  84. Song, H.-J., Ming, G. L., He, Z., et al. (1998) Conversion of neuronal growth cone responses from repulsion to attraction by cyclic nucleotides. Science 281, 515–518.

    Article  Google Scholar 

  85. Forscher, P. and Smith, S. J. (1988) Actions of cytochalasins on the organization of actin filaments and microtubules in a neuronal growth cone. J. Cell Biol. 107, 1505–1516.

    Article  PubMed  CAS  Google Scholar 

  86. Forscher, P., Lin, C. H., and Thompson, C. (1992) Novel form of growth cone motility involving site-directed actin filament assembly. Nature 357, 515–518.

    Article  PubMed  CAS  Google Scholar 

  87. Lin, C. H. and Forscher, P. (1995) Growth cone advance is inversely proportional to retrograde F-actin flow. Neuron 14, 763–771.

    Article  PubMed  CAS  Google Scholar 

  88. Lin, C. H., Espreafico, E. M., Mooseker, M. S., and Forscher, P. (1996) Myosin drives retrograde F-actin flow in neuronal growth cones. Neuron 16, 769–782.

    Article  PubMed  CAS  Google Scholar 

  89. Tanaka, E. and Sabry, J. (1995) Making the connection: cytoskeletal rearrangements during growth cone guidance. Cell 83, 171–176.

    Article  PubMed  CAS  Google Scholar 

  90. Hall, A. (1998) Rho GTPase and the actin cytoskeleton. Science 279, 509–514.

    Article  PubMed  CAS  Google Scholar 

  91. Luo, L., Liao, Y. J., Jan, L. Y., and Jan, Y. N. (1994) Distinct morphogenetic functions of similar small GTPases: Drosophila Dracl is involved in axonal outgrowth and myoblast fusion. Genes Dey. 8, 1787–1802.

    Article  CAS  Google Scholar 

  92. Luo, L., Heusch, T. K., Ackerman, L., et al. (1996) Differential effects of the rac 1 GTPase on Purkinje cell axons and dendritic trunks and spines. Nature 379, 837–840.

    Article  PubMed  CAS  Google Scholar 

  93. Jin, Z. and Strittmatter, S. M. (1997) Rac1 mediates collapsin-1-induced growth cone collapse. J. Neurosci. 17, 6256–6263.

    PubMed  CAS  Google Scholar 

  94. Kozma, R., Sarner, S., Ahmed, S., and Lim, L. (1997) Rho family GTPase and neuronal growth cone remodelling: relationship between increased complexity induced by Cdc42Hs, Racl and acetylcholine and collapse induced by RhoA and lysophosphatidic Acid. Mol. Cell. Biol. 17, 1201–1211.

    PubMed  CAS  Google Scholar 

  95. Nishida, E., Maekawa, S., and Sakai, H. (1984) Cofilin, a protein in porcine brain that binds to actin filaments and inhibits their interactions with myosin and tropomyosin. Biochemistry 23, 5307–5313.

    Article  PubMed  CAS  Google Scholar 

  96. Bamburg, J. R. and Bray, D. (1987) Distribution and cellular localization of actin depolymerizing factor. J. Cell Biol. 105, 2817–2825.

    Article  PubMed  CAS  Google Scholar 

  97. Yang, N., Higuchi, O., Ohashi, K., et al. (1998) Cofilin phosphorylation by LIMkinase 1 and its role in rac-mediated actin reorganization. Nature 393, 809–812.

    Article  PubMed  CAS  Google Scholar 

  98. Arber, S., Barbayannis, F. A., Hauser, H., et al. (1998) Regulation of actin dynamics through phosphorylation of cofilin by LIM-kinase. Nature 393, 805–809.

    Article  PubMed  CAS  Google Scholar 

  99. Mild, H., Suetsugu, S., and Takenawa, T. (1998) WAVE, a novel WASP family protein involved in actin reorganization induced by rac. EMBO J. 17, 6932–6941.

    Article  Google Scholar 

  100. Frangiskakis, J. M., Ewart, A. K., Morris, C. A., et al. (1996) LIM-kinase 1 Hemizygosity implicated in impaired visuospatial constructive cognition. Cell 86, 59–69.

    Article  PubMed  CAS  Google Scholar 

  101. Dai, J. and Sheetz, M. P. (1995) Axon membrane flows from the growth cone to the cell body. Cell 83, 693–701.

    Article  PubMed  CAS  Google Scholar 

  102. Tsui, H. C., Ris, H., and Klein, W. L. (1983) Ultrastructural networks in growth cones and neuntes of cultured central nervous system neurons. Proc. Natl. Acad. Sci. USA 80, 5779–5783.

    Article  PubMed  CAS  Google Scholar 

  103. Lockerbie, R. O., Miller, V. E., and Pfenninger, K. H. (1991) Regulated plasmalemmal expansion in nerve growth cones. J. Cell Biol. 112, 1215–1227.

    Article  PubMed  CAS  Google Scholar 

  104. Cheng, T. P. and Reese, T. S. (1987) Recycling of plasmalemma in chick tectal growth cones. J. Neurosci. 7, 1752–1759.

    PubMed  CAS  Google Scholar 

  105. Igarashi, M., Tagaya, M., and Komiya, Y. (1997) The soluble N-ethylmaleimidesensitive factor attached protein receptor complex in growth cones: molecular aspects of the axon terminal development. J. Neurosci. 17, 1460–1470.

    PubMed  CAS  Google Scholar 

  106. Igarashi, M., Kozaki, S., Terakawa, S., et al. (1996) Growth cone collapse and inhibition of neurite growth by botulinum neurotoxin C 1: a t-SNARE is involved in axonal growth. J. Cell Biol. 34, 205–215.

    Article  Google Scholar 

  107. Osen-Sand, A., Catsicas, M., Staple, J. K., et al. (1993) Inhibition of axonal growth by SNAP-25 antisense oligonucleotides in vitro and in vivo. Nature 364, 445–448.

    Article  PubMed  CAS  Google Scholar 

  108. Torre, E., McNiven, M. A., and Urrutia, R. (1994) Dynamin I antisense oligonucleotide treatment prevents neurite formation in cultured hippocampal neurons. J. Biol. Chem. 269, 32411–32417.

    PubMed  CAS  Google Scholar 

  109. Mundigl, O., Ochoa, G. C., David, C., et al. (1998) Amphiphysin I antisense oligonucleotides inhibit neurite outgrowth in cultured hippocampal neurons. J. Neurosci. 18, 93–103.

    PubMed  CAS  Google Scholar 

  110. Fan, J. and Raper, J. A. (1995) Localized collapsing cues can steer growth cones without inducing their full collapse. Neuron 14, 263–274.

    Article  PubMed  CAS  Google Scholar 

  111. Feiner, L., Koppel, A., Kobayashi, H., and Raper, J., A. (1997) Secreted chick semaphorins bind recombinant neuropilin with similar affinities but bind different subsets of neurons in situ. Neuron 19, 539–545.

    Article  PubMed  CAS  Google Scholar 

  112. He, Z. and Tessier-Lavigne, M. (1997) Neuropilin is a receptor for the axonal chemorepellent semaphorin III. Cell 90, 739–751.

    Article  PubMed  CAS  Google Scholar 

  113. Kolodkin, A. L., Levengood, D. V., Rowe, E. G., et al. (1997) Neuropilin is a semaphorin III receptor. Cell 90, 753–762.

    Article  PubMed  CAS  Google Scholar 

  114. Takahashi, T., Nakamura, F., and Strittmatter, S. M. (1997) Neuronal and non-neuronal collapsin-1 binding sites in developing chick are distinct from other semaphorin binding sites. J. Neurosci. 17, 9183–9193.

    PubMed  CAS  Google Scholar 

  115. Kitsukawa, T., Shimizu, M., Saubo, M., et al. (1997) Neuropilin-semaphorin III/Dmediated chemorepulsive signals play a crucial role in peripheral nerve projection in mice. Neuron 19, 995–1005.

    Article  PubMed  CAS  Google Scholar 

  116. Takahashi, T., Nakamura, F., Jin, Z., Kalb, R. G., and Strittmatter, S. M. (1998) Semaphorins A and E act as antagonists of neuropilin-1 and agonists of neuropilin2 receptors. Nature Neurosci. 1, 487–493.

    CAS  Google Scholar 

  117. Nakamura, E, Tanaka, M., Takahashi, T., Kalb, R. G., and Strittmatter, S. M. (1998) Neuropilin-1 extracellular domains mediate semaphorin D/III-induced growth cone collapse. Neuron 21, 1093–1100.

    Article  PubMed  CAS  Google Scholar 

  118. Kawakami, A., Kitsukawa, T., Takagi, S., and Fujisawa, H. (1996) Developmentally regulated expression of a cell surface protein, neuropilin, in the mouse nervous system. J. Neurobiol. 29, 1–17.

    Article  PubMed  CAS  Google Scholar 

  119. Kolodkin, A. L. and Ginty, D. D. (1997) Steering clear of semaphorins: neuropilins sound the retreat. Neuron 19, 1159–1162.

    Article  PubMed  CAS  Google Scholar 

  120. Chen, H., Chedotal, A., He, Z., Goodman, C. S., and Marc, T.-L. (1997) Neuropilin-2, a novel member of the neuropilin family, is a high affinity receptor for the semaphorins sema E and sema IV but not sema III. Neuron 19, 547–559.

    Article  PubMed  CAS  Google Scholar 

  121. Giger, R. J., Urquhart, E. R., Gillespie, S. K. H., et al. (1998) Neuropilin-2 is a receptor for semaphorin IV: insight into the structural basis of receptor function and specificity. Neuron 21, 1079–1092.

    Article  PubMed  CAS  Google Scholar 

  122. Chen, H., He, Z., Bagri, A., and Tessier-Lavigne, M. (1998) Semaphorin-neuropilin interactions underlying sympathetic axon responses to class III semaphorins. Neuron 21, 1283–1290.

    Article  Google Scholar 

  123. 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.

    Article  PubMed  CAS  Google Scholar 

  124. Wang, L.-H. and Strittmatter, S. M. (1997) Brain CRMP forms heterotetramers similar to liver dihidropyrimidinase. J. Neumchem. 69, 2261–2269.

    Article  CAS  Google Scholar 

  125. 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.

    PubMed  CAS  Google Scholar 

  126. Fan, J., Mansfield, S. G., Redmond, T., Gordon-Weeks, P. R., and Raper, J. A. (1993) The organization of F-actin and microtubules in growth cones exposed to a brain-derived collapsing factor. J. Cell Biol. 121, 867–878.

    Article  PubMed  CAS  Google Scholar 

  127. Davis, S., Gale, N. W., Aldrich, T. H., et al. (1994) Ligands for EPH-related receptor tyrosine kinases that require membrane attachment or clustering for activity. Science 266, 816–819.

    Article  PubMed  CAS  Google Scholar 

  128. Stein, E., Cerretti, D. P., and Daniel, T. 0. (1996) Ligand activation of Elk receptor tyrosine kinase promotes its association with Grb10 and Grb2 in vascular endothelial cells. J. Biol. Chem. 271, 23588–23593.

    Article  PubMed  CAS  Google Scholar 

  129. Pandey, A., Lazar, D. F., Saltiel, A. R., and Dixit, V. M. (1994) Activation of the Eck receptor protein kinase stimulates phosphatidylinositol 3 kinase activity. J. Biol. Chem. 269, 30154–30157.

    PubMed  CAS  Google Scholar 

  130. Holland, S. J., Gale, N. W., Mbamalu, G., et al. (1996) Bidirectional signalling through the EPH-family receptor Nuk and its transmembrane ligands. Nature 383, 722–725.

    Article  PubMed  CAS  Google Scholar 

  131. Bruckner, K., Pasquale, E. B., and Klein, R. (1997) Tyrosine phosphorylation of transmembrane ligands for Eph receptors. Science 275, 1640–1643.

    Article  PubMed  CAS  Google Scholar 

  132. Bandtlow, C. E., Schmidt, M. F., Hassinger, T. D., Schwab, M. E., and Kater, S. B. (1993) Role of intracellular calcium in NI-35-evoked collapse of neuronal growth cones. Science 259, 80–83.

    Article  PubMed  CAS  Google Scholar 

  133. Igarashi, M., Strittmatter, S. M., Vartanian, T., and Fishman, M. C. (1993) Mediation by G proteins of signals that cause collapse of growth cones. Science 259, 77–79.

    Article  PubMed  CAS  Google Scholar 

  134. Kindt, R. M. and Lander, A. D. (1995) Pertussis toxin specifically inhibits growth cone guidance by a mechanism independent of direct G protein inactivation. Neuron 15, 79–88.

    Article  PubMed  CAS  Google Scholar 

  135. Collins, B. E., Yang, L. J.-S., Mukhopadhyay, G., et al. (1997) Sialic acid specificity of myelin-associated glycoprotein binding. J. Biol. Chem. 272, 1248–1255.

    Article  PubMed  CAS  Google Scholar 

  136. Aktories, K. and Just, I. (1995) In vitro ADP-ribosylation of Rho by bacterial ADPribosyltransferases. Methods Enzymol. 256, 184–195.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Li-Hsien Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alyson Fournier
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fumio Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Takuya Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Robert G. Kalb
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Stephen M. Strittmatter
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Departments of Neurology and Pharmacology, Yale University School of Medicine, New Haven, CT, USA

    Robert G. Kalb MD

  2. Department of Neurology, Yale University School of Medicine, New Haven, CT, USA

    Stephen M. Strittmatter MD, PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Springer Science+Business Media New York

About this chapter

Cite this chapter

Wang, LH., Fournier, A., Nakamura, F., Takahashi, T., Kalb, R.G., Strittmatter, S.M. (2000). Transduction of Inhibitory Signals by the Axonal Growth Cone. In: Kalb, R.G., Strittmatter, S.M. (eds) Neurobiology of Spinal Cord Injury. Contemporary Neuroscience. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-200-5_6

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-200-5_6

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-126-4

  • Online ISBN: 978-1-59259-200-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation