Regulation of Spine Development by Semaphorin3A through Cyclin-Dependent Kinase 5 Phosphorylation of Collapsin Response Mediator Protein 1

Autor: Yoshio Goshima, Hiroshi Usui, Jérôme Honnorat, Fumio Nakamura, Masahiko Taniguchi, Nicole Thomasset, Toshio Ohshima, Asa Morita, Pappachan E. Kolattukudy, Naoya Yamashita, Takuya Takahashi, Yutaka Uchida, Kohtaro Takei
Rok vydání: 2007
Předmět:
Zdroj: The Journal of Neuroscience. 27:12546-12554
ISSN: 1529-2401
0270-6474
Popis: 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 fromcrmp1+/−mice, Sema3A increased the density of clusters of synapsin I and postsynaptic density-95, but this increase was markedly attenuated incrmp1−/−mice. This attenuation was also seen incyclin-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, intocrmp1−/−neurons rescued the defect in Sema3A responsiveness. The Golgi-impregnation method showed that thecrmp1−/−layer V cortical neurons showed a lower density of synaptic bouton-like structures and that this phenotype had genetic interaction withsema3A. These findings suggest that Sema3A-induced spine development is regulated by phosphorylation of CRMP1 by Cdk5.
Databáze: OpenAIRE