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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

281 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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