Abstract
Semaphorin-3A (Sema3A), a member of class 3 semaphorins, regulates axon and dendrite guidance in the nervous system. How Sema3A and its receptors plexin-As and neuropilins regulate neuronal guidance is unknown. We observed that in fyn- and cdk5-deficient mice, Sema3A-induced growth cone collapse responses were attenuated compared to their heterologous controls. Cdk5 is associated with plexin-A2 through the active state of Fyn. Sema3A promotes Cdk5 activity through phosphorylation of Tyr15, a phosphorylation site with Fyn. A Cdk5 mutant (Tyr15 to Ala) shows a dominant-negative effect on the Sema3A-induced collapse response. The sema3A gene shows strong interaction with fyn for apical dendrite guidance in the cerebral cortex. We propose a signal transduction pathway in which Fyn and Cdk5 mediate neuronal guidance regulated by Sema3A.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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COS Cells
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Cerebral Cortex / drug effects
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Cerebral Cortex / physiology*
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Chick Embryo
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Cyclin-Dependent Kinase 5
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Cyclin-Dependent Kinases / deficiency*
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Cyclin-Dependent Kinases / genetics
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Cyclin-Dependent Kinases / physiology*
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Dendrites / drug effects
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Dendrites / physiology*
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Enzyme Inhibitors / pharmacology
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Glycoproteins / physiology*
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Growth Cones / drug effects
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Growth Cones / physiology
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Humans
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Mice
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Mice, Mutant Strains
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Proto-Oncogene Proteins / deficiency*
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / physiology*
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Proto-Oncogene Proteins c-fyn
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Semaphorin-3A
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Signal Transduction / drug effects
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Signal Transduction / physiology*
Substances
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Enzyme Inhibitors
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Glycoproteins
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Proto-Oncogene Proteins
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Semaphorin-3A
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FYN protein, human
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Fyn protein, mouse
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Proto-Oncogene Proteins c-fyn
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Cyclin-Dependent Kinase 5
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CDK5 protein, human
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Cdk5 protein, mouse
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Cyclin-Dependent Kinases