title: Fyn and Cdk5 mediate semaphorin-3A signaling, which is involved in regulation of dendrite orientation in cerebral cortex.
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.
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University School of Medicine, Yokohama, Japan. yukio.sasaki@pharmac.med.yokohama-cu.ac.jp
authors.forename: Yukio
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Chi
authors.initials: C
authors.lastname: Cheng
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Uchida
authors.forename: Oumi
authors.initials: O
authors.lastname: Nakajima
authors.forename: Toshio
authors.initials: T
authors.lastname: Ohshima
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yagi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakayama
authors.forename: Reiji
authors.initials: R
authors.lastname: Kishida
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kudo
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Ohno
authors.forename: Fumio
authors.initials: F
authors.lastname: Nakamura
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Goshima
mesh_terms: 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*
chemical_list: 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