TY - JOUR
T1 - Fyn and Cdk5 mediate semaphorin-3A signaling, which is involved in regulation of dendrite orientation in cerebral cortex
AU - Sasaki, Yukio
AU - Cheng, Chi
AU - Uchida, Yutaka
AU - Nakajima, Oumi
AU - Ohshima, Toshio
AU - Yagi, Takeshi
AU - Taniguchi, Masahiko
AU - Nakayama, Takashi
AU - Kishida, Reiji
AU - Kudo, Yoshihisa
AU - Ohno, Shigeaki
AU - Nakamura, Fumio
AU - Goshima, Yoshio
N1 - Funding Information:
The authors thank Takahiro Nagase (Kazusa DNA Research Institute) for providing human Plex-A2 cDNA, Hajime Fujisawa (Nagoya University) for providing mouse NP-1 cDNA, Michinari Hamaguchi (Nagoya University) for providing chick c-src cDNA, and Ashok B. Kulkarni (National Institute of Dental and Craniofacial Research) for providing cdk5-deficient mice and cDNAs of Cdk5 and p35. The authors also thank Toshio Terashima (Kobe University) for advice on analysis for Golgi impregnation and Rachael L. Neve (Harvard Medical School and McLean Hospital) for providing the HSV vector and helper virus. We thank Megumi Noda and Motoyuki Shimonaka (Science University of Tokyo) for support of the pharmacological assay and Nobuyuki Fukushima (Hokkaido University) for LPA collapse assay. We also thank our laboratory members, especially Yoshinobu Sugiyama, Chanxia Li, and Emiko Kuramata for performing cell culture, Sema3A preparation, and DNA constructs. This work was supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology, Japan (to Y.S. and F.N.) and CREST (Core Research for Evolutional Science and Technology) of JST (Japan Science and Technology Corporation) (to Y.G.).
PY - 2002/8/29
Y1 - 2002/8/29
N2 - 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.
AB - 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.
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U2 - 10.1016/S0896-6273(02)00857-7
DO - 10.1016/S0896-6273(02)00857-7
M3 - Article
C2 - 12372285
AN - SCOPUS:18644374595
SN - 0896-6273
VL - 35
SP - 907
EP - 920
JO - Neuron
JF - Neuron
IS - 5
ER -