Regulation of spine development by semaphorin3A through cyclin-dependent kinase 5 phosphorylation of collapsin response mediator protein 1.
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.
Yamashita
Naoya
N
Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Morita
Asa
A
Uchida
Yutaka
Y
Nakamura
Fumio
F
Usui
Hiroshi
H
Ohshima
Toshio
T
Taniguchi
Masahiko
M
Honnorat
Jérôme
J
Thomasset
Nicole
N
Takei
Kohtaro
K
Takahashi
Takuya
T
Kolattukudy
Pappachan
P
Goshima
Yoshio
Y
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D006224:Cricetinae; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics / Q000378:metabolism*; D049229:Dendritic Spines / Q000378:metabolism* / Q000648:ultrastructure; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D040121:Semaphorin-3A / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D016704:Synapsins / Q000235:genetics / Q000378:metabolism; D013570:Synaptic Membranes / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D000098855:Collapsin Response Mediator Protein 1
D051360:Cyclin-Dependent Kinase 5; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D040121:Semaphorin-3A; D016704:Synapsins; C502872:Crmp1 protein, mouse; D000098855:Collapsin Response Mediator Protein 1; C501447:Dlg4 protein, mouse; C495906:Cdk5 protein, mouse