Regulation of N-type Voltage-Gated Calcium Channels and Presynaptic Function by Cyclin-Dependent Kinase 5

Susan C. Su, Jinsoo Seo, Jen Q. Pan, Benjamin Adam Samuels, Andrii Rudenko, Maria Ericsson, Rachael L. Neve, David T. Yue, Li Huei Tsai

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish (US)
Pages (from-to)675-687
Number of pages13
JournalNeuron
Volume75
Issue number4
DOIs
StatePublished - Aug 23 2012

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Regulation of N-type Voltage-Gated Calcium Channels and Presynaptic Function by Cyclin-Dependent Kinase 5'. Together they form a unique fingerprint.

Cite this