PKCdelta 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 PKCdelta, a member of novel PKC expressing in cortical neurons, could stabilize p35 by direct phosphorylation. PKCdelta attenuated the degradation of p35 but not its mutant derivative, which could not be phosphorylated by PKCdelta. Down-regulation of PKCdelta 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, PKCdelta could be activated by the promigratory factor brain-derived neurotrophic factor (BDNF) and was required for the activation of Cdk5 by BDNF. Both PKCdelta and p35 were required for the promigratory effect of BDNF on cultured newborn neurons. Thus, PKCdelta may promote cortical radial migration through maintaining the proper level of p35 in newborn neurons.
Zhao
Chun-tao
CT
State Key Laboratory of Neurobiology, Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Li
Kun
K
Li
Jun-tao
JT
Zheng
Wang
W
Liang
Xu-jun
XJ
Geng
An-qi
AQ
Li
Ning
N
Yuan
Xiao-bing
XB
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D002465:Cell Movement; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D051360:Cyclin-Dependent Kinase 5; D015536:Down-Regulation / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D051745:Protein Kinase C-delta / Q000235:genetics / Q000502:physiology*; D055550:Protein Stability; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D019208:Brain-Derived Neurotrophic Factor; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; C089495:neuronal Cdk5 activator (p25-p35); D051360:Cyclin-Dependent Kinase 5; D051745:Protein Kinase C-delta