PKCδ regulates cortical radial migration by stabilizing the Cdk5 activator p35

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. Here, we show that PKC delta, a member of novel PKC expressing in cortical neurons, could stabilize p35 by direct phosphorylation. PKC delta attenuated the degradation of p35 but not its mutant derivative, which could not be phosphorylated by PKC delta. Down-regulation of PKC delta by in utero electroporation of specific small interference RNA (siRNA) severely impaired the radial migration of cortical neurons. This migration defect was similar to that caused by down-regulation of p35 and could be prevented by cotransfection with the wild-type but not the mutant p35. Furthermore, PKC delta could be activated by the promigratory factor brain-derived neurotrophic factor (BDNF) and was required for the activation of Cdk5 by BDNF. Both PKC delta and p35 were required for the promigratory effect of BDNF on cultured newborn neurons. Thus, PKC delta may promote cortical radial migration through maintaining the proper level of p35 in newborn neurons.