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Tropomodulin3 is a novel Akt2 effector regulating insulin-stimulated GLUT4 exocytosis through cortical actin remodeling

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  • Chun-Yan Lim

    (Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, Agency for Science, Technology and Research)

  • Xuezhi Bi

    (Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, Agency for Science, Technology and Research
    Bioprocessing Technology Institute, Agency for Science, Technology and Research)

  • Donghai Wu

    (The Key Laboratory of Regenerative Biology and The Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences)

  • Jae Bum Kim

    (National Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Seoul National University)

  • Peter W. Gunning

    (Oncology Research Unit, School of Medical Sciences, University of New South Wales)

  • Wanjin Hong

    (Institute of Molecular and Cell Biology, Agency for Science, Technology and Research)

  • Weiping Han

    (Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, Agency for Science, Technology and Research)

Abstract

Akt2 and its downstream effectors mediate insulin-stimulated GLUT4-storage vesicle (GSV) translocation and fusion with the plasma membrane (PM). Using mass spectrometry, we identify actin-capping protein Tropomodulin 3 (Tmod3) as an Akt2-interacting partner in 3T3-L1 adipocytes. We demonstrate that Tmod3 is phosphorylated at Ser71 on insulin-stimulated Akt2 activation, and Ser71 phosphorylation is required for insulin-stimulated GLUT4 PM insertion and glucose uptake. Phosphorylated Tmod3 regulates insulin-induced actin remodelling, an essential step for GSV fusion with the PM. Furthermore, the interaction of Tmod3 with its cognate tropomyosin partner, Tm5NM1 is necessary for GSV exocytosis and glucose uptake. Together these results establish Tmod3 as a novel Akt2 effector that mediates insulin-induced cortical actin remodelling and subsequent GLUT4 membrane insertion. Our findings suggest that defects in cytoskeletal remodelling may contribute to impaired GLUT4 exocytosis and glucose uptake.

Suggested Citation

  • Chun-Yan Lim & Xuezhi Bi & Donghai Wu & Jae Bum Kim & Peter W. Gunning & Wanjin Hong & Weiping Han, 2015. "Tropomodulin3 is a novel Akt2 effector regulating insulin-stimulated GLUT4 exocytosis through cortical actin remodeling," Nature Communications, Nature, vol. 6(1), pages 1-15, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms6951
    DOI: 10.1038/ncomms6951
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