Abstract
Semaphorin 3A is a chemorepulsive axonal guidance molecule that depolymerizes the actin cytoskeleton and collapses growth cones of dorsal root ganglia neurons. Here we investigate the role of LIM-kinase 1, which phosphorylates an actin-depolymerizing protein, cofilin, in semaphorin 3A-induced growth cone collapse. Semaphorin 3A induced phosphorylation and dephosphorylation of cofilin at growth cones sequentially. A synthetic cell-permeable peptide containing a cofilin phosphorylation site inhibited LIM-kinase in vitro and in vivo, and essentially suppressed semaphorin 3A-induced growth cone collapse. A dominant-negative LIM kinase, which could not be activated by PAK or ROCK, suppressed the collapsing activity of semaphorin 3A. Phosphorylation of cofilin by LIM-kinase may be a critical signaling event in growth cone collapse by semaphorin 3A.
MeSH terms
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Actin Depolymerizing Factors
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Actins / metabolism*
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Amino Acid Sequence
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Animals
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Blotting, Western
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Cells, Cultured
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Ganglia, Spinal / cytology
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Genetic Vectors / genetics
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Glycoproteins / metabolism*
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Growth Cones / physiology*
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Growth Cones / ultrastructure
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Humans
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Lim Kinases
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Mice
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Microfilament Proteins / genetics
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Microfilament Proteins / metabolism*
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Microscopy, Fluorescence
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Molecular Sequence Data
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Nerve Growth Factors / metabolism
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Neurons, Afferent / cytology
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Neurons, Afferent / enzymology*
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Peptides / metabolism
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Phosphorylation
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Protein Kinases / genetics
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Protein Kinases / metabolism*
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Semaphorin-3A
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Transfection
Substances
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Actin Depolymerizing Factors
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Actins
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Glycoproteins
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Microfilament Proteins
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Nerve Growth Factors
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Peptides
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Recombinant Proteins
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Semaphorin-3A
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Protein Kinases
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LIMK1 protein, human
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Lim Kinases
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Limk1 protein, mouse