Cdk5-mediated phosphorylation of CRMP-2 enhances its interaction with CaV2.2

Joel M. Brittain, Yuying Wang, Omotore Eruvwetere, Rajesh Khanna

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

The axon/dendrite specification collapsin response mediator protein-2 (CRMP-2) bidirectionally regulates N-type voltage-gated Ca2+ channels (CaV2.2). But how cyclin dependent kinase 5 (Cdk5)-mediated phosphorylation of CRMP-2 affects its interaction/regulation with CaV2.2 is unknown. CRMP-2-mediated enhancement of currents via CaV2.2 was not observed with a Cdk5 phospho-null CRMP-2-S522A mutant or in cells expressing an inactive Cdk5. Concomitant knockdown of endogenous CRMP2 and overexpression of CRMP2-S522A mutant refractory to knockdown phenocopied the reduction in Ca2+ influx while the Rho kinase CRMP2-T555A mutant was ineffective. Cdk5-phosphorylated CRMP-2 had increased association with CaV2.2. These results identify an important role for Cdk5 in CRMP2-mediated CaV2.2 regulation. Structured summary of protein interactions: Gsk3b phosphorylates Crmp2by phosphatase assay (View interaction) Crmp2 physically interacts with Cav2.2 by anti tag coimmunoprecipitation (View interaction)

Original languageEnglish (US)
Pages (from-to)3813-3818
Number of pages6
JournalFEBS Letters
Volume586
Issue number21
DOIs
Publication statusPublished - Nov 2 2012
Externally publishedYes

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Keywords

  • CaV2.2
  • Cdk5
  • CRMP-2
  • Interaction
  • Phosphorylation
  • RhoK

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Genetics
  • Molecular Biology
  • Structural Biology

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