title: Cdk5-mediated phosphorylation of CRMP-2 enhances its interaction with CaV2.2.
abstract: The axon/dendrite specification collapsin response mediator protein-2 (CRMP-2) bidirectionally regulates N-type voltage-gated Ca(2+) 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 Ca(2+) 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.
authors.affiliation: Program in Medical Neuroscience, Paul and Carole Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, United States.
authors.forename: Joel M
authors.initials: JM
authors.lastname: Brittain
authors.forename: Yuying
authors.initials: Y
authors.lastname: Wang
authors.forename: Omotore
authors.initials: O
authors.lastname: Eruvwetere
authors.forename: Rajesh
authors.initials: R
authors.lastname: Khanna
mesh_terms: D000818:Animals; D020864:Calcium Channels, N-Type / Q000235:genetics* / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D047468:Immunoprecipitation; D036341:Intercellular Signaling Peptides and Proteins; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D015398:Signal Transduction; D014162:Transfection
chemical_list: C503279:Cacna1b protein, rat; D020864:Calcium Channels, N-Type; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; C095114:collapsin response mediator protein-2; D051360:Cyclin-Dependent Kinase 5; C495907:Cdk5 protein, rat