Cdk5 phosphorylates and stabilizes p27kip1 contributing to actin organization and cortical neuronal migration.
p27(kip1), a cyclin-dependent kinase (CDK) inhibitor (CKI), generally suppresses CDK activity in proliferating cells. Although another role of p27 in cell migration has been recently suggested in vitro, the physiological importance of p27 in cell migration remains elusive, as p27-deficient mice have not shown any obvious migration-defect-related phenotypes. Here, we show that Cdk5, an unconventional neuronal CDK, phosphorylates and stabilizes p27 as an upstream regulator, maintaining the amount of p27 in post-mitotic neurons. In vivo RNA interference (RNAi) experiments showed that reduced amounts of p27 caused inhibition of cortical neuronal migration and decreased the amount of F-actin in the processes of migrating neurons. The Cdk5-p27 pathway activates an actin-binding protein, cofilin, which is also shown to be involved in cortical neuronal migration in vivo. Our findings shed light on a previously unknown new relationship between CDK and CKI in G0-arrested cells that regulates cytoskeletal reorganization and neuronal migration during corticogenesis.
Kawauchi
Takeshi
T
Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Chihama
Kaori
K
Nabeshima
Yo-ichi
Y
Hoshino
Mikio
M
D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D051360:Cyclin-Dependent Kinase 5 / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D008954:Models, Biological; D009474:Neurons / Q000502:physiology*; D010766:Phosphorylation; D014162:Transfection
D051339:Actin Depolymerizing Factors; D000199:Actins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051360:Cyclin-Dependent Kinase 5