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

Jessica B. A. Sadler, Christopher A. Lamb, Cassie R. Welburn, Iain S. Adamson, Dimitrios Kioumourtzoglou, Nai-Wen Chi, Gwyn W. Gould, Nia J. Bryant

Research output: Contribution to journalArticle

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.

LanguageEnglish
Article number4710
Number of pages7
JournalScientific Reports
Volume9
DOIs
Publication statusPublished - 18 Mar 2019

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Tankyrases
Facilitative Glucose Transport Proteins
Adipocytes
Insulin
Ubiquitination
Glucose
Muscle Cells
Homeostasis
Deubiquitinating Enzymes
Enzymes
Proteins

Keywords

  • glucose homeostasis
  • GLUT4
  • insulin
  • glucose transport

Cite this

Sadler, J. B. A., Lamb, C. A., Welburn, C. R., Adamson, I. S., Kioumourtzoglou, D., Chi, N-W., ... Bryant, N. J. (2019). The deubiquitinating enzyme USP25 binds tankyrase and regulates trafficking of the facilitative glucose transporter GLUT4 in adipocytes. Scientific Reports, 9, [4710]. https://doi.org/10.1038/s41598-019-40596-5
Sadler, Jessica B. A. ; Lamb, Christopher A. ; Welburn, Cassie R. ; Adamson, Iain S. ; Kioumourtzoglou, Dimitrios ; Chi, Nai-Wen ; Gould, Gwyn W. ; Bryant, Nia J. / The deubiquitinating enzyme USP25 binds tankyrase and regulates trafficking of the facilitative glucose transporter GLUT4 in adipocytes. In: Scientific Reports. 2019 ; Vol. 9.
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The deubiquitinating enzyme USP25 binds tankyrase and regulates trafficking of the facilitative glucose transporter GLUT4 in adipocytes. / Sadler, Jessica B. A.; Lamb, Christopher A.; Welburn, Cassie R.; Adamson, Iain S.; Kioumourtzoglou, Dimitrios; Chi, Nai-Wen; Gould, Gwyn W.; Bryant, Nia J.

In: Scientific Reports, Vol. 9, 4710, 18.03.2019.

Research output: Contribution to journalArticle

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