Cdk5-Dependent Mst3 Phosphorylation and Activity Regulate Neuronal Migration through RhoA Inhibition

• DOI: 10.1523/jneurosci.5449-13.2014
• Publication Date: 2014-05-28T17:38:52Z
• Authors: Jing Tang; Jacque P.K. Ip; Tao Ye; Yu-Pong Ng; Wing-Ho Yung; Zhenguo Wu; Weiqun Fang; Amy K.Y. Fu; Nancy Y. Ip
• Keywords: Cyclin-dependent kinase 5

The radial migration of newborn neurons is critical for the lamination cerebral cortex. Proper neuronal requires precise and rapid reorganization actin microtubule cytoskeleton. However, underlying signaling mechanisms controlling cytoskeletal are not well understood. Here, we show that Mst3, a serine/threonine kinase highly expressed in developing mouse brain, essential final positioning neocortex. Mst3 silencing by utero electroporation perturbed multipolar-to-bipolar transition migrating significantly retards migration. Although activity its functions morphogenesis migration, it regulated via phosphorylation at Ser79 kinase, cyclin-dependent 5 (Cdk5). Our results regulates through modulating RhoA, Rho-GTPase reorganization. phosphorylates RhoA Ser26, thereby negatively regulating GTPase RhoA. Importantly, knockdown successfully rescues defect Mst3-knockdown cortices. findings collectively suggest Cdk5–Mst3 RhoA-dependent dynamics.