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Updated: Jun 18, 2026
12:01
Induction of Protein Deletion Through In Utero Electroporation to Define Deficits in Neuronal Migration in Transgenic Models
Published on: January 12, 2015
PKCdelta regulates cortical radial migration by stabilizing the Cdk5 activator p35
Chun-tao Zhao1, Kun Li, Jun-tao Li
1State Key Laboratory of Neurobiology, Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Summary
Protein kinase C delta (PKCdelta) stabilizes p35, a key Cdk5 activator, promoting neuron migration during brain development. This finding clarifies PKCdelta
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Cyclin-dependent kinase 5 (Cdk5) and its activator p35 are crucial for cortical neuron development.
- Regulation of Cdk5 activity by extracellular and intracellular signals during cortical morphogenesis is not fully understood.
Purpose of the Study:
- To investigate the role of Protein Kinase C delta (PKCdelta) in regulating p35 and its impact on cortical neuron migration.
- To elucidate the signaling pathway involving PKCdelta, p35, and brain-derived neurotrophic factor (BDNF) in cortical development.
Main Methods:
- Utilized in utero electroporation with small interference RNA (siRNA) to down-regulate PKCdelta expression in developing cortical neurons.
- Employed mutant p35 derivatives to assess the role of PKCdelta phosphorylation.
- Investigated the activation of Cdk5 and its promigratory effects using cultured newborn neurons and BDNF stimulation.
Main Results:
- PKCdelta directly phosphorylates and stabilizes p35, preventing its degradation.
- Down-regulation of PKCdelta impairs cortical neuron radial migration, mimicking p35 deficiency.
- PKCdelta is required for BDNF-induced Cdk5 activation and neuronal migration.
- PKCdelta and p35 are essential for the promigratory effects of BDNF.
Conclusions:
- PKCdelta promotes cortical radial migration by maintaining adequate p35 levels in developing neurons.
- PKCdelta acts as a critical regulator in the BDNF-mediated signaling pathway essential for cortical development.
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