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

Research output: Contribution to journalArticle

80 Scopus citations

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 CaMKIIδ abolished insulin-dependent Myo1c phosphorylation in vivo. CaMKII activity was increased upon insulin treatment and the CaMKII inhibitors CN21 and KN-62 or the Ca2+ 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 (US)
Pages (from-to)384-398
Number of pages15
JournalCell Metabolism
Volume8
Issue number5
DOIs
StatePublished - Nov 5 2008

Keywords

  • HUMDISEASE
  • SIGNALING
  • SYSBIO

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

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