Cdk-mediated phosphorylation of the Kvβ2 auxiliary subunit regulates Kv1 channel axonal targeting

Hélène Vacher, Jae Won Yang, Oscar Cerda, Amapola Autillo-Touati, Bénédicte Dargent, James Trimmer

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46 Scopus citations

Abstract

Kv1 channels are concentrated at specific sites in the axonal membrane, where they regulate neuronal excitability. Establishing these distributions requires regulated dissociation of Kv1 channels from the neuronal trafficking machinery and their subsequent insertion into the axonal membrane. We find that the auxiliary Kvβ2 subunit of Kv1 channels purified from brain is phosphorylated on serine residues 9 and 31, and that cyclin-dependent kinase (Cdk) - mediated phosphorylation at these sites negatively regulates the interaction of Kvβ2 with the microtubule plus end - tracking protein EB1. Endogenous Cdks, EB1, and Kvβ2 phosphorylated at serine 31 are colocalized in the axons of cultured hippocampal neurons, with enrichment at the axon initial segment (AIS). Acute inhibition of Cdk activity leads to intracellular accumulation of EB1, Kvβ2, and Kv1 channel subunits within the AIS. These studies reveal a new regulatory mechanism for the targeting of Kv1 complexes to the axonal membrane through the reversible Cdk phosphorylation-dependent binding of Kvβ2 to EB1.

Original languageEnglish (US)
Pages (from-to)813-824
Number of pages12
JournalJournal of Cell Biology
Volume192
Issue number5
DOIs
StatePublished - Mar 7 2011

ASJC Scopus subject areas

  • Cell Biology

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    Vacher, H., Yang, J. W., Cerda, O., Autillo-Touati, A., Dargent, B., & Trimmer, J. (2011). Cdk-mediated phosphorylation of the Kvβ2 auxiliary subunit regulates Kv1 channel axonal targeting. Journal of Cell Biology, 192(5), 813-824. https://doi.org/10.1083/jcb.201007113