CaMKII-mediated phosphorylation of the myosin motor Myo1c is required for insulin-stimulated GLUT4 translocation in adipocytes

Ming Fai Yip, Georg Ramm, Mark Larance, Kyle L. Hoehn, Mark C. Wagner, Michael Guilhaus, David E. James (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    85 Citations (Scopus)

    Abstract

    The unconventional myosin Myo1c has been implicated in insulin-regulated GLUT4 translocation to the plasma membrane in adipocytes. We show that Myo1c undergoes insulin-dependent phosphorylation at S701. Phosphorylation was accompanied by enhanced 14-3-3 binding and reduced calmodulin binding. Recombinant CaMKII phosphorylated Myo1c in vitro and siRNA knockdown of CaMKIIdelta abolished insulin-dependent Myo1c phosphorylation in vivo. CaMKII activity was increased upon insulin treatment and the CaMKII inhibitors CN21 and KN-62 or the Ca(2+) chelator BAPTA-AM blocked insulin-dependent Myo1c phosphorylation and insulin-stimulated glucose transport in adipocytes. Myo1c ATPase activity was increased after CaMKII phosphorylation in vitro and after insulin stimulation of CHO/IR/IRS-1 cells. Expression of wild-type Myo1c, but not S701A or ATPase dead mutant K111A, rescued the inhibition of GLUT4 translocation by siRNA-mediated Myo1c knockdown. These data suggest that insulin regulates Myo1c function via CaMKII-dependent phosphorylation, and these events play a role in insulin-regulated GLUT4 trafficking in adipocytes likely involving Myo1c motor activity.
    Original languageEnglish
    Pages (from-to)384-398
    Number of pages15
    JournalCell Metabolism
    Volume8
    Issue number5
    DOIs
    Publication statusPublished - 5 Nov 2008

    Keywords

    • Animals
    • 14-3-3 Proteins
    • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
    • Myosins
    • Mice
    • Glucose Transporter Type 4
    • Insulin
    • Calcium-Calmodulin-Dependent Protein Kinase Type 2
    • Myosin Type I
    • Phosphorylation
    • Adipocytes
    • Cell Line
    • Protein Transport
    • Cricetinae

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