An Actin Filament Population Defined by the Tropomyosin Tpm3.1 Regulates Glucose Uptake

Anthony J. Kee, Lingyan Yang, Christine A. Lucas, Michael J. Greenberg, Nick Martel, Gary M. Leong, William E. Hughes, Gregory J. Cooney, David E. James, E. Michael Ostap, Weiping Han, Peter W. Gunning, Edna C. Hardeman

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Actin has an ill-defined role in the trafficking of GLUT4 glucose transporter vesicles to the plasma membrane (PM). We have identified novel actin filaments defined by the tropomyosin Tpm3.1 at glucose uptake sites in white adipose tissue (WAT) and skeletal muscle. In Tpm 3.1-overexpressing mice, insulin-stimulated glucose uptake was increased; while Tpm3.1-null mice they were more sensitive to the impact of high-fat diet on glucose uptake. Inhibition of Tpm3.1 function in 3T3-L1 adipocytes abrogates insulin-stimulated GLUT4 translocation and glucose uptake. In WAT, the amount of filamentous actin is determined by Tpm3.1 levels and is paralleled by changes in exocyst component (sec8) and Myo1c levels. In adipocytes, Tpm3.1 localizes with MyoIIA, but not Myo1c, and it inhibits Myo1c binding to actin. We propose that Tpm3.1 determines the amount of cortical actin that can engage MyoIIA and generate contractile force, and in parallel limits the interaction of Myo1c with actin filaments. The balance between these actin filament populations may determine the efficiency of movement and/or fusion of GLUT4 vesicles with the PM. Actin's role in GLUT4 glucose transporter trafficking is unclear. We have identified novel actin filaments defined by the tropomyosin Tpm3.1 that regulates GLUT4 trafficking and glucose uptake. MyoIIA and Myo1c are known regulators of GLUT4 trafficking. Tpm3.1 has been shown to recruit MyoIIA to actin filaments and here we show that it inhibits Myo1c binding. The balance between Tpm3.1/MyoIIA and Tpm3.1-free/Myo1c actin filament populations may determine the efficiency of movement and/or fusion of GLUT4 vesicles with the plasma membrane.

Original languageEnglish
Pages (from-to)691-711
Number of pages21
JournalTraffic
Volume16
Issue number7
DOIs
StatePublished - Jul 1 2015

Keywords

  • Actin cytoskeleton
  • GLUT4
  • Glucose uptake
  • Myosins
  • Tropomyosin

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