On Nov 24, 2009, the Proceedings of the National Academy of Sciences published online a research article from Institute of Neuroscience (ION) entitled "PKCδ Regulates Cortical Radial Migration by Stabilizing the Cdk5 Activator P35”. This work was carried out by graduate students ZHAO Chun-tao, LI Kun , ZHENG Wang, LI Juntao , LIANG Xunjun , GENG An-qi  and LI Ning  from the laboratory of Dr. YUAN Xiao-bing . 

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 PKC, 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 PKC could stabilize p35 by direct phosphorylation and by attenuating its degradation. Downregulation of PKC 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, PKC could be activated by the pro-migratory factor brain-derived neurotrophic factor (BDNF) and was required for the activation of Cdk5 by BDNF. Both PKC 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).

PKCδ Regulates Cortical Radial Migration by Stabilizing the Cdk5 Activator P35 (Picture provided by ION)