NCAM-dependent neurite outgrowth is inhibited in neurons from Fyn-minus mice.
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.
Department of Biochemistry, University of North Carolina School of Medicine, Chapel Hill 27599-7260.
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D000818:Animals; D001483:Base Sequence; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis / Q000502:physiology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000502:physiology*; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D007700:Kinetics; D007739:L Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D008969:Molecular Sequence Data; D016501:Neurites / Q000502:physiology* / Q000648:ultrastructure; D009474:Neurons / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D051076:Proto-Oncogene Proteins c-fyn; D014162:Transfection
D015816:Cell Adhesion Molecules, Neuronal; D017931:DNA Primers; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn