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Publication : PKCdelta regulates cortical radial migration by stabilizing the Cdk5 activator p35.

First Author  Zhao CT Year  2009
Journal  Proc Natl Acad Sci U S A Volume  106
Issue  50 Pages  21353-8
PubMed ID  19965374 Mgi Jnum  J:155821
Mgi Id  MGI:4415763 Doi  10.1073/pnas.0812872106
Citation  Zhao CT, et al. (2009) PKCdelta regulates cortical radial migration by stabilizing the Cdk5 activator p35. Proc Natl Acad Sci U S A 106(50):21353-8
abstractText  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.
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