PKCδ Regulates Cortical Radial Migration by Stabilizing the Cdk5 Activator P35

Time:2009-11-28

 

On Nov 24, 2009, the Proceedings of the National Academy of Sciences published online a research article from ION entitled "PKCδ Regulates Cortical Radial Migration by Stabilizing the Cdk5 Activator P35". This work was carried out by graduate students Chun-tao Zhao, Kun Li, Wang Zheng, Jun-tao Li, Xun-jun Liang, An-qi Geng and Ning Li from the laboratory of Dr. Xiao-bing Yuan. 

Cyclin-dependent kinase 5 (Cdk5) and its activator p35 are critical for radial migration and lamination of cortical neurons. However, how this kinase is regulated by extracellular and intracellular signals during cortical morphogenesis remains unclear. Chun-tao Zhao and colleagues found that PKCδ, a novel PKC member expresed in cortical neurons, may promote cortical radial migration through maintaining the proper level of p35 in newborn neurons. They found that PKCδ could stabilize p35 by direct phosphorylation and by attenuating its degradation. Downregulation of PKCδ by in utero electroporation of specific small interference RNA (siRNA) severely impaired the radial migration of newborn cortical neurons, similar to the migration defect caused by downregulation of p35. Furthermore, PKCδ could be activated by the pro-migratory factor brain-derived neurotrophic factor (BDNF) and was required for the activation of Cdk5 by BDNF. Both PKCδ  and p35 were required for the pro-migratory effect of BDNF on cultured newborn neurons. These results reveal a new mechanism for the regulation of cortical radial migration during development.  This work was supported by 973 projects (2006CB806600, 2006CB943903), National Natural Science Foundation of China (30625023, 30721004), and Chinese Academy of Sciences (KSCX2-YW-R-103).

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