Fyn and Cdk5 mediate semaphorin-3A signaling, which is involved in regulation of dendrite orientation in cerebral cortex

Yukio Sasaki, Chi Cheng, Yutaka Uchida, Oumi Nakajima, Toshio Ohshima, Takeshi Yagi, Masahiko Taniguchi, Takashi Nakayama, Reiji Kishida, Yoshihisa Kudo, Shigeaki Ohno, Fumio Nakamura, Yoshio Goshima

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264 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)907-920
Number of pages14
JournalNeuron
Volume35
Issue number5
DOIs
Publication statusPublished - 2002 Aug 29
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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    Sasaki, Y., Cheng, C., Uchida, Y., Nakajima, O., Ohshima, T., Yagi, T., Taniguchi, M., Nakayama, T., Kishida, R., Kudo, Y., Ohno, S., Nakamura, F., & Goshima, Y. (2002). Fyn and Cdk5 mediate semaphorin-3A signaling, which is involved in regulation of dendrite orientation in cerebral cortex. Neuron, 35(5), 907-920. https://doi.org/10.1016/S0896-6273(02)00857-7