Abstract
Collapsin response mediator protein 1 (CRMP1) is one of the CRMP family members that mediates signal transduction of axonal guidance and neuronal migration. We show here evidence that CRMP1 is involved in semaphorin3A (Sema3A)-induced spine development in the cerebral cortex. In the cultured cortical neurons from crmp1+/- mice, Sema3A increased the density of clusters of synapsin I and postsynaptic density-95, but this increase was markedly attenuated in crmp1-/- mice. This attenuation was also seen in cyclin-dependent kinase 5 (cdk5)-/- neurons. Furthermore, the introduction of wild-type CRMP1 but not CRMP1-T509A/S522A, (Thr 509 and Ser 522 were replaced by Ala), a mutant that cannot be phosphorylated by Cdk5, into crmp1-/- neurons rescued the defect in Sema3A responsiveness. The Golgi-impregnation method showed that the crmp1-/- layer V cortical neurons showed a lower density of synaptic bouton-like structures and that this phenotype had genetic interaction with sema3A. These findings suggest that Sema3A-induced spine development is regulated by phosphorylation of CRMP1 by Cdk5.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Differentiation / physiology*
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Cells, Cultured
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Cerebral Cortex / growth & development*
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Cerebral Cortex / metabolism
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Cerebral Cortex / ultrastructure
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Cricetinae
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Cyclin-Dependent Kinase 5 / genetics
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Cyclin-Dependent Kinase 5 / metabolism*
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Dendritic Spines / metabolism*
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Dendritic Spines / ultrastructure
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Disks Large Homolog 4 Protein
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Guanylate Kinases
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Inbred ICR
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Mice, Knockout
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Phosphorylation
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Presynaptic Terminals / metabolism
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Presynaptic Terminals / ultrastructure
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Semaphorin-3A / genetics
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Semaphorin-3A / metabolism*
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Synapses / genetics
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Synapses / metabolism
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Synapses / ultrastructure
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Synapsins / genetics
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Synapsins / metabolism
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Synaptic Membranes / genetics
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Synaptic Membranes / metabolism
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Synaptic Membranes / ultrastructure
Substances
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Crmp1 protein, mouse
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Disks Large Homolog 4 Protein
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Dlg4 protein, mouse
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Nerve Tissue Proteins
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Semaphorin-3A
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Synapsins
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Cyclin-Dependent Kinase 5
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Cdk5 protein, mouse
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Guanylate Kinases