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PMID: 7962063 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

NCAM-dependent neurite outgrowth is inhibited in neurons from Fyn-minus mice.

The Journal of cell biology ·Vol. 127 ·No. 3 ·1994-11-00 ·Pages 825-33

Beggs HE, Soriano P, Maness PF

Abstract

Src-related nonreceptor protein tyrosine kinases in nerve growth cones (p59fyn, pp60c-src, and pp62c-yes) are potential intracellular signaling molecules for cell adhesion molecule-directed axonal growth. To determine whether src-related tyrosine kinases mediate NCAM-dependent neurite outgrowth, cultures of cerebellar and sensory neurons from fyn-, src-, and yes- minus mice were analyzed for neurite outgrowth on monolayers of NCAM140-transfected L fibroblasts. NCAM-dependent neurite outgrowth was selectively inhibited in cultures of cerebellar and dorsal root ganglion neurons from fyn-, but not src- or yes- mice. Neurite outgrowth by fyn-, src-, or yes- neurons on untransfected fibroblast monolayers was unaffected, indicating that these kinases do not contribute significantly to axon growth on at least some integrins or other adhesive substrates present on fibroblasts. This study demonstrates that p59fyn is an essential component of the NCAM signaling pathway leading to axonal growth.

Related Genes
MeSH Terms
Animals Base Sequence Cell Adhesion Molecules, Neuronal/biosynthesis,physiology Cells, Cultured Cerebellum/physiology DNA Primers Enzyme-Linked Immunosorbent Assay Kinetics L Cells Mice Mice, Inbred C57BL Mice, Neurologic Mutants Molecular Sequence Data Neurites/physiology,ultrastructure Neurons/physiology Neurons, Afferent/physiology Polymerase Chain Reaction Protein-Tyrosine Kinases/genetics Proto-Oncogene Proteins/biosynthesis,genetics Proto-Oncogene Proteins c-fyn Transfection
Chemicals
Cell Adhesion Molecules, Neuronal DNA Primers Proto-Oncogene Proteins Protein-Tyrosine Kinases Fyn protein, mouse Proto-Oncogene Proteins c-fyn
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Beggs H E
Department of Biochemistry, University of North Carolina School of Medicine, Chapel Hill 27599-7260.
Soriano P
Maness P F
References (70)
70 references, click to expand
  1. Altered expression of pp60c-src induced by peripheral nerve injury.
    J Comp Neurol. 1992 Jan 8;315(2):171-7 PMID: 1372011
  2. pp59fyn and pp62c-yes are enriched in SH-SY5Y neuroblastoma growth cones but do not associate to the 38 kDa protein which complexes with pp60c src and pp60c-srcN.
    FEBS Lett. 1993 Oct 11;332(1-2):27-30 PMID: 7691658
  3. Genetic deletion of a neural cell adhesion molecule variant (N-CAM-180) produces distinct defects in the central nervous system.
    Neuron. 1993 Dec;11(6):1163-74 PMID: 8274281
  4. The neural cell adhesion molecule N-CAM enhances L1-dependent cell-cell interactions.
    J Cell Biol. 1990 Jan;110(1):193-208 PMID: 2295682
  5. Guidance of optic axons in vivo by a preformed adhesive pathway on neuroepithelial endfeet.
    Dev Biol. 1984 Dec;106(2):485-99 PMID: 6500184
  6. Osteoclasts express high levels of pp60c-src in association with intracellular membranes.
    J Cell Biol. 1992 Nov;119(4):1003-13 PMID: 1385441
  7. Molecular cloning of two abundant protein tyrosine kinases in Torpedo electric organ that associate with the acetylcholine receptor.
    J Biol Chem. 1993 Nov 25;268(33):25152-61 PMID: 8227079
  8. Differentiation of PC12 cells with v-src: comparison with nerve growth factor.
    J Neurosci Res. 1989 Sep;24(1):49-58 PMID: 2810396
  9. At least 27 alternatively spliced forms of the neural cell adhesion molecule mRNA are expressed during rat heart development.
    Mol Cell Biol. 1991 Mar;11(3):1654-61 PMID: 1996115
  10. Studies of adhesion molecules mediating interactions between cells of peripheral nervous system indicate a major role for L1 in mediating sensory neuron growth on Schwann cells in culture.
    J Cell Biol. 1988 Jul;107(1):341-51 PMID: 3292543
  11. Functional characterization of chondroitin sulfate proteoglycans of brain: interactions with neurons and neural cell adhesion molecules.
    J Cell Biol. 1993 Feb;120(3):815-24 PMID: 8425902
  12. A threshold effect of the major isoforms of NCAM on neurite outgrowth.
    Nature. 1990 Feb 1;343(6257):464-6 PMID: 2153939
  13. Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice.
    Cell. 1991 Feb 22;64(4):693-702 PMID: 1997203
  14. Membrane glycoprotein IV (CD36) is physically associated with the Fyn, Lyn, and Yes protein-tyrosine kinases in human platelets.
    Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7844-8 PMID: 1715582
  15. Alterations in the Xenopus retinotectal projection by antibodies to Xenopus N-CAM.
    Dev Biol. 1988 Sep;129(1):217-30 PMID: 3044878
  16. Functional coupling of the src-family protein tyrosine kinases p59fyn and p53/56lyn with the interleukin 2 receptor: implications for redundancy and pleiotropism in cytokine signal transduction.
    Proc Natl Acad Sci U S A. 1993 May 1;90(9):4201-5 PMID: 8483935
  17. Characterization of NCAM diversity in cultured neurons.
    FEBS Lett. 1993 Jun 21;324(3):337-40 PMID: 8405377
  18. Neurite outgrowth on muscle cell surfaces involves extracellular matrix receptors as well as Ca2+-dependent and -independent cell adhesion molecules.
    Proc Natl Acad Sci U S A. 1987 Apr;84(8):2555-9 PMID: 3031688
  19. Neuron-glia relationship during granule cell migration in developing cerebellar cortex. A Golgi and electronmicroscopic study in Macacus Rhesus.
    J Comp Neurol. 1971 Mar;141(3):283-312 PMID: 4101340
  20. Fate of GAP-43 in ascending spinal axons of DRG neurons after peripheral nerve injury: delayed accumulation and correlation with regenerative potential.
    J Neurosci. 1991 Dec;11(12):3738-51 PMID: 1836017
  21. Direct activation of second messenger pathways mimics cell adhesion molecule-dependent neurite outgrowth.
    J Cell Biol. 1992 Aug;118(3):663-70 PMID: 1379246
  22. Identification of a heparin binding domain of the neural cell adhesion molecule N-CAM using synthetic peptides.
    Neuron. 1989 Feb;2(2):1157-65 PMID: 2624745
  23. Increased neurite outgrowth induced by inhibition of protein tyrosine kinase activity in PC12 pheochromocytoma cells.
    J Neurochem. 1993 Jun;60(6):2134-44 PMID: 7684068
  24. Association of the fyn protein-tyrosine kinase with the T-cell antigen receptor.
    Proc Natl Acad Sci U S A. 1990 Jun;87(11):4358-62 PMID: 2190221
  25. Immunoelectron microscopic localization of the neural cell adhesion molecules L1 and N-CAM during postnatal development of the mouse cerebellum.
    J Cell Biol. 1987 Jul;105(1):569-76 PMID: 3301870
  26. Recombinant myelin-associated glycoprotein confers neural adhesion and neurite outgrowth function.
    Neuron. 1989 Sep;3(3):377-85 PMID: 2484339
  27. Initial events of myelination involve Fyn tyrosine kinase signalling.
    Nature. 1994 Feb 10;367(6463):572-6 PMID: 7509042
  28. Impaired neurite outgrowth of src-minus cerebellar neurons on the cell adhesion molecule L1.
    Neuron. 1994 Apr;12(4):873-84 PMID: 7512817
  29. Neurite outgrowth in response to transfected N-CAM changes during development and is modulated by polysialic acid.
    Neuron. 1990 Aug;5(2):209-19 PMID: 2200449
  30. Inhibition of tyrosine phosphorylation potentiates substrate-induced neurite growth.
    J Neurobiol. 1992 Jul;23(5):468-80 PMID: 1279111
  31. Expression of the unique NCAM VASE exon is independently regulated in distinct tissues during development.
    J Cell Biol. 1990 Nov;111(5 Pt 1):2089-96 PMID: 1699951
  32. pp59fyn mutant mice display differential signaling in thymocytes and peripheral T cells.
    Cell. 1992 Sep 4;70(5):741-50 PMID: 1387588
  33. Kinetics of homophilic binding by embryonic and adult forms of the neural cell adhesion molecule.
    Proc Natl Acad Sci U S A. 1983 Sep;80(18):5762-6 PMID: 6577452
  34. Association between the PDGF receptor and members of the src family of tyrosine kinases.
    Cell. 1990 Aug 10;62(3):481-92 PMID: 1696179
  35. Nonreceptor protein tyrosine kinases associated with neuronal development.
    Dev Neurosci. 1992;14(4):257-70 PMID: 1295748
  36. Increased expression of pp60c-src protein-tyrosine kinase during peripheral nerve regeneration.
    J Neurosci Res. 1991 Feb;28(2):299-309 PMID: 1709691
  37. Localization of p62c-yes protein in mammalian neural tissues.
    Oncogene. 1991 Oct;6(10):1725-33 PMID: 1923498
  38. v-src genes stimulate neurite outgrowth in pheochromocytoma (PC12) variants unresponsive to neurotrophic factors.
    J Neurosci Res. 1989 Sep;24(1):67-71 PMID: 2810397
  39. Neurite extension and protein tyrosine phosphorylation elicited by inducible expression of the v-src oncogene in a PC12 cell line.
    Exp Cell Res. 1991 Aug;195(2):423-31 PMID: 2070824
  40. Expression of a novel form of the fyn proto-oncogene in hematopoietic cells.
    New Biol. 1989 Oct;1(1):66-74 PMID: 2488273
  41. Neural cell adhesion molecules influence second messenger systems.
    Neuron. 1989 Jul;3(1):13-20 PMID: 2559759
  42. pp60c-src is developmentally regulated in the neural retina.
    Cell. 1984 Feb;36(2):249-57 PMID: 6198092
  43. Impaired long-term potentiation, spatial learning, and hippocampal development in fyn mutant mice.
    Science. 1992 Dec 18;258(5090):1903-10 PMID: 1361685
  44. Characterization of isolated mouse cerebellar cell populations in vitro.
    J Neuroimmunol. 1981 Dec;1(4):457-70 PMID: 7050171
  45. Neurite outgrowth in response to transfected N-CAM and N-cadherin reveals fundamental differences in neuronal responsiveness to CAMs.
    Neuron. 1991 Feb;6(2):247-58 PMID: 1993122
  46. Alternatively spliced mRNAs code for different polypeptide chains of the chicken neural cell adhesion molecule (N-CAM).
    J Cell Biol. 1986 Jan;102(1):189-93 PMID: 3001098
  47. Evidence for heterophilic adhesion of embryonic retinal cells and neuroblastoma cells to substratum-adsorbed NCAM.
    J Cell Biol. 1992 Jun;117(6):1311-20 PMID: 1607391
  48. Cell adhesion molecules, second messengers and axonal growth.
    Curr Opin Neurobiol. 1992 Oct;2(5):595-601 PMID: 1422115
  49. Regional localization of Fyn in adult brain; studies with mice in which fyn gene was replaced by lacZ.
    Oncogene. 1993 Dec;8(12):3343-51 PMID: 8247536
  50. Biosynthesis, membrane association, and release of N-CAM-120, a phosphatidylinositol-linked form of the neural cell adhesion molecule.
    J Cell Biol. 1987 Dec;105(6 Pt 1):2489-500 PMID: 3693391
  51. Inactivation of the N-CAM gene in mice results in size reduction of the olfactory bulb and deficits in spatial learning.
    Nature. 1994 Feb 3;367(6462):455-9 PMID: 8107803
  52. Extracellular matrix molecules and their receptors: functions in neural development.
    Annu Rev Neurosci. 1991;14:531-70 PMID: 1851608
  53. Differentiation of PC12 phaeochromocytoma cells induced by v-src oncogene.
    Nature. 1985 Aug 8-14;316(6028):557-9 PMID: 2993898
  54. Differential roles of multiple adhesion molecules in cell migration: granule cell migration in cerebellum.
    Experientia. 1990 Sep 15;46(9):892-9 PMID: 2209798
  55. p59fyn in rat brain is localized in developing axonal tracts and subpopulations of adult neurons and glia.
    Oncogene. 1993 Jun;8(6):1429-36 PMID: 8502471
  56. Axon growth is enhanced by NCAM lacking the VASE exon when expressed in either the growth substrate or the growing axon.
    J Neurosci Res. 1993 Jun 15;35(3):327-45 PMID: 8350393
  57. Development of neuronal polarity: GAP-43 distinguishes axonal from dendritic growth cones.
    Nature. 1988 Dec 15;336(6200):672-4 PMID: 3059197
  58. The cellular neurobiology of neuronal development: the cerebellar granule cell.
    Brain Res. 1988 Jan-Mar;472(1):77-101 PMID: 3277691
  59. Defective T cell receptor signaling in mice lacking the thymic isoform of p59fyn.
    Cell. 1992 Sep 4;70(5):751-63 PMID: 1516132
  60. Tyrosine phosphorylation in early embryonic growth cones.
    J Neurosci. 1993 Aug;13(8):3421-32 PMID: 7688039
  61. Developmental regulation of protein tyrosine phosphorylation in rat brain.
    J Neurosci Res. 1988 Oct-Dec;21(2-4):473-9 PMID: 2464082
  62. Molecular mechanisms of axon growth and guidance.
    Annu Rev Cell Biol. 1991;7:117-59 PMID: 1687312
  63. The VASE exon downregulates the neurite growth-promoting activity of NCAM 140.
    Nature. 1992 Apr 30;356(6372):791-3 PMID: 1574117
  64. Genetic analysis of a Drosophila neural cell adhesion molecule: interaction of fasciclin I and Abelson tyrosine kinase mutations.
    Cell. 1990 Feb 23;60(4):565-75 PMID: 2406026
  65. c-src gene product in developing rat brain is enriched in nerve growth cone membranes.
    Proc Natl Acad Sci U S A. 1988 Jul;85(14):5001-5 PMID: 2455889
  66. pp60c-src in the developing cerebellum.
    Mol Cell Biol. 1985 Jan;5(1):27-32 PMID: 3920510
  67. Cell Type-specific Effects of the Neural Adhesion Molecules L1 and N-CAM on Diverse Second Messenger Systems.
    Eur J Neurosci. 1992;4(10):896-909 PMID: 12106425
  68. Molecular Association of the Neural Adhesion Molecules L1 and N-CAM in the Surface Membrane of Neuroblastoma Cells is Shown by Chemical Cross-linking.
    Eur J Neurosci. 1991 Jul;3(7):634-640 PMID: 12106471
  69. Tubulin is phosphorylated at tyrosine by pp60c-src in nerve growth cone membranes.
    J Cell Biol. 1990 Nov;111(5 Pt 1):1959-70 PMID: 1699949
  70. Characterisation of the second messenger pathway underlying neurite outgrowth stimulated by FGF.
    Development. 1994 Jun;120(6):1685-93 PMID: 8050374
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
Published
1994-11-00
Pages
825-33
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2120232
Subset
IM
Grants
NINDS NIH HHS · NS 26620 · United States
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