Regulation of N-type Voltage-Gated Calcium Channels and Presynaptic Function by Cyclin-Dependent Kinase 5
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Su-2012-Regulation of N-type.pdf
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Author(s)
Su, Susan C.
Seo, Jinsoo
Pan, Jen Q.
Samuels, Benjamin Adam
Rudenko, Andrii
Ericsson, Maria
Neve, Rachael L.
Yue, David T.
Tsai, Li-Huei
Date Issued
August 2012
Journal
Neuron
Publisher
Elsevier
Citation
Su, Susan C., Jinsoo Seo, Jen Q. Pan, Benjamin Adam Samuels, Andrii Rudenko, Maria Ericsson, Rachael L. Neve, David T. Yue, and Li-Huei Tsai. “Regulation of N-Type Voltage-Gated Calcium Channels and Presynaptic Function by Cyclin-Dependent Kinase 5.” Neuron 75, no. 4 (August 2012): 675–687. © 2012 Elsevier Inc.
Version
Final published version
Abstract
N-type voltage-gated calcium channels localize to presynaptic nerve terminals and mediate key events including synaptogenesis and neurotransmission. While several kinases have been implicated in the modulation of calcium channels, their impact on presynaptic functions remains unclear. Here we report that the N-type calcium channel is a substrate for cyclin-dependent kinase 5 (Cdk5). The pore-forming α[subscript 1] subunit of the N-type calcium channel is phosphorylated in the C-terminal domain, and phosphorylation results in enhanced calcium influx due to increased channel open probability. Phosphorylation of the N-type calcium channel by Cdk5 facilitates neurotransmitter release and alters presynaptic plasticity by increasing the number of docked vesicles at the synaptic cleft. These effects are mediated by an altered interaction between N-type calcium channels and RIM1, which tethers presynaptic calcium channels to the active zone. Collectively, our results highlight a molecular mechanism by which N-type calcium channels are regulated by Cdk5 to affect presynaptic function.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
McGovern Institute for Brain Research at MIT
Picower Institute for Learning and Memory
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1016/j.neuron.2012.06.023
