The effect of Cyclin-dependent kinase 5 on voltage-dependent calcium channels in PC12 cells varies according to channel type and cell differentiation state
Article first published online: 19 MAY 2014
© 2014 International Society for Neurochemistry
Journal of Neurochemistry
Volume 130, Issue 4, pages 498–506, August 2014
How to Cite
J. Neurochem. (2014) 130, 498–506.
- Issue published online: 7 AUG 2014
- Article first published online: 19 MAY 2014
- Accepted manuscript online: 25 APR 2014 11:13AM EST
- Manuscript Accepted: 16 APR 2014
- Manuscript Revised: 12 APR 2014
- Manuscript Received: 25 FEB 2014
- MEXT. Grant Number: 25290024
- cyclin-dependent kinase 5;
- nerve growth factor;
- PC12 cell;
- voltage-dependent calcium channel
Cyclin-dependent kinase 5 (Cdk5) is a Ser/Thr kinase that plays an important role in the release of neurotransmitter from pre-synaptic terminals triggered by Ca2+ influx into the pre-synaptic cytoplasm through voltage-dependent Ca2+ channels (VDCCs). It is reported that Cdk5 regulates L-, P/Q-, or N-type VDCC, but there is conflicting data as to the effect of Cdk5 on VDCC activity. To clarify the mechanisms involved, we examined the role of Cdk5 in regulating the Ca2+-channel property of VDCCs, using PC12 cells expressing endogenous, functional L-, P/Q-, and N-type VDCCs. The Ca2+ influx, induced by membrane depolarization with high K+, was monitored with a fluorescent Ca2+ indicator protein in both undifferentiated and nerve growth factor (NGF)-differentiated PC12 cells. Overall, Ca2+ influx was increased by expression of Cdk5-p35 in undifferentiated PC12 cells but suppressed in differentiated PC12 cells. Moreover, we found that different VDCCs are distinctly regulated by Cdk5-p35 depending on the differentiation states of PC12 cells. These results indicate that Cdk5-p35 regulates L-, P/Q-, or N-type VDCCs in a cellular context-dependent manner.
Calcium (Ca2+) influx through voltage-dependent Ca2+ channels (VDCCs) triggers neurotransmitter release from pre-synaptic terminal of neurons. The channel activity of VDCCs is regulated by Cdk5-p35, a neuronal Ser/Thr kinase. However, there have been debates about the regulation of VDCCs by Cdk5. Using PC12 cells, we show that Cdk5-p35 regulates VDCCs in a type (L, P/Q, and N) and differentiation-dependent manner. NGF = nerve growth factor.