Fyn and Cdk5 mediate semaphorin-3A signaling, which is involved in regulation of dendrite orientation in cerebral cortex.
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.
Sasaki
Yukio
Y
Department of Molecular Pharmacology and Neurobiology, Yokohama City University School of Medicine, Yokohama, Japan. yukio.sasaki@pharmac.med.yokohama-cu.ac.jp
Cheng
Chi
C
Uchida
Yutaka
Y
Nakajima
Oumi
O
Ohshima
Toshio
T
Yagi
Takeshi
T
Taniguchi
Masahiko
M
Nakayama
Takashi
T
Kishida
Reiji
R
Kudo
Yoshihisa
Y
Ohno
Shigeaki
S
Nakamura
Fumio
F
Goshima
Yoshio
Y
D000818:Animals; D019556:COS Cells; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D002642:Chick Embryo; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D003712:Dendrites / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006023:Glycoproteins / Q000502:physiology*; D020439:Growth Cones / Q000187:drug effects / Q000502:physiology; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D051076:Proto-Oncogene Proteins c-fyn; D040121:Semaphorin-3A; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D004791:Enzyme Inhibitors; D006023:Glycoproteins; D011518:Proto-Oncogene Proteins; D040121:Semaphorin-3A; C494957:FYN protein, human; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D051360:Cyclin-Dependent Kinase 5; C495905:CDK5 protein, human; C495906:Cdk5 protein, mouse; D018844:Cyclin-Dependent Kinases