• Open Access

Insulin-Regulated Trafficking of GLUT4 Requires Ubiquitination

Authors

  • Christopher A. Lamb,

    1. Henry Wellcome Laboratory of Cell Biology, Institute of Molecular, Cell & Systems Biology, College of Medical, Veterinary and Life Sciences, Davidson Building, University of Glasgow, Glasgow G12 8QQ, United Kingdom
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    • These authors contributed equally.

  • Rebecca K. McCann,

    1. Henry Wellcome Laboratory of Cell Biology, Institute of Molecular, Cell & Systems Biology, College of Medical, Veterinary and Life Sciences, Davidson Building, University of Glasgow, Glasgow G12 8QQ, United Kingdom
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    • These authors contributed equally.

  • Jacqueline Stöckli,

    1. Diabetes and Obesity Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney NSW 2010, Australia
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  • David E. James,

    1. Diabetes and Obesity Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney NSW 2010, Australia
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  • Nia J. Bryant

    Corresponding author
    1. Henry Wellcome Laboratory of Cell Biology, Institute of Molecular, Cell & Systems Biology, College of Medical, Veterinary and Life Sciences, Davidson Building, University of Glasgow, Glasgow G12 8QQ, United Kingdom
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Nia J. Bryant, nia.bryant@glasgow.ac.uk

Abstract

A major consequence of insulin binding its receptor on fat and muscle cells is translocation of the facilitative glucose transporter GLUT4 from an intracellular store to the cell surface where it serves to clear glucose from the bloodstream. Sorting of GLUT4 into its insulin-sensitive store requires the GGA [Golgi-localized, γ-ear-containing, ADP ribosylation factor (ARF)-binding] adaptor proteins, but the signal on GLUT4 to direct this sorting step is unknown. Here, we have identified a role for ubiquitination of GLUT4 in this process. We demonstrate that GLUT4 is ubiquitinated in 3T3-L1 adipocytes, and that a ubiquitin-resistant version fails to translocate to the cell surface of these cells in response to insulin. Our data support a model in which ubiquitination acts as a signal for the trafficking of GLUT4 from the endosomal/trans-Golgi network (TGN) system into its intracellular storage compartment, from where it is mobilized to the cell surface in response to insulin.

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