The deubiquitinating enzyme USP25 binds tankyrase and regulates trafficking of the facilitative glucose transporter GLUT4 in adipocytes

Sadler, J. B.A., Lambert, C. A., Welburn, C. R., Adamson, I. S., Kioumourtzoglou, D., Chi, N.-W., Gould, G. W. and Bryant, N. J. (2019) The deubiquitinating enzyme USP25 binds tankyrase and regulates trafficking of the facilitative glucose transporter GLUT4 in adipocytes. Scientific Reports, 9(1), 4710. (doi: 10.1038/s41598-019-40596-5) (PMID:30886164) (PMCID:PMC6423145)

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Abstract

Key to whole body glucose homeostasis is the ability of fat and muscle cells to sequester the facilitative glucose transporter GLUT4 in an intracellular compartment from where it can be mobilized in response to insulin. We have previously demonstrated that this process requires ubiquitination of GLUT4 while numerous other studies have identified several molecules that are also required, including the insulin-responsive aminopeptidase IRAP and its binding partner, the scaffolding protein tankyrase. In addition to binding IRAP, Tankyrase has also been shown to bind the deubiquinating enzyme USP25. Here we demonstrate that USP25 and Tankyrase interact, and colocalise with GLUT4 in insulin-sensitive cells. Furthermore depletion of USP25 from adipocytes reduces cellular levels of GLUT4 and concomitantly blunts the ability of insulin to stimulate glucose transport. Collectively, these data support our model that sorting of GLUT4 into its insulin-sensitive store involves a cycle of ubiquitination and subsequent deubiquitination.

Item Type:Articles
Additional Information:This work was supported by an MRC grant to N.J.B. and G.W.G. a PhD studentship from The Wellcome Trust to C.A.L. and a Prize Fellowship from the Lister Institute of Preventive Medicine to N.J.B.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Welburn, Dr Cassie and Sadler, Miss Jessica and Kioumourtzoglou, Mr Dimitrios and Gould, Professor Gwyn and Bryant, Dr Nia and Lambert, Christopher
Authors: Sadler, J. B.A., Lambert, C. A., Welburn, C. R., Adamson, I. S., Kioumourtzoglou, D., Chi, N.-W., Gould, G. W., and Bryant, N. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Scientific Reports
Publisher:Nature Publishing Group
ISSN:2045-2322
ISSN (Online):2045-2322
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Scientific Reports 9(1):4710
Publisher Policy:Reproduced under a Creative Commons License

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