Endosomal sorting of GLUT4 and Gap1 is conserved between yeast and insulin-sensitive cells

Shewan, A. M., McCann, R. K., Lamb, C. A., Stirrat, L., Kioumourtzoglou, D., Adamson, I. S., Verma, S., James, D. E. and Bryant, N. J. (2013) Endosomal sorting of GLUT4 and Gap1 is conserved between yeast and insulin-sensitive cells. Journal of Cell Science, 126(7), pp. 1576-1582. (doi:10.1242/jcs.114371)

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Abstract

The insulin-regulated trafficking of the facilitative glucose transporter GLUT4 in human fat and muscle cells and the nitrogen-regulated trafficking of the general amino acid permease Gap1 in the yeast Saccharomyces cerevisiae share several common features: Both Gap1 and GLUT4 are nutrient transporters that are mobilised to the cell surface from an intracellular store in response to an environmental cue; both are polytopic membrane proteins harbouring amino acid targeting motifs in their C-terminal tails that are required for their regulated trafficking; ubiquitylation of both Gap1 and GLUT4 plays an important role in their regulated trafficking, as do the ubiquitin-binding GGA (Golgi-localised, γ-ear-containing, ARF-binding) adaptor proteins. Here, we find that when expressed heterologously in yeast, human GLUT4 is subject to nitrogen-regulated trafficking in an ubiquitin-dependent manner similar to Gap1. In addition, by expressing a GLUT4/Gap1 chimeric protein in adipocytes we show that the carboxy-tail of Gap1 directs intracellular sequestration and insulin-regulated trafficking in adipocytes. These findings demonstrate that the trafficking signals and their cognate molecular regulatory machinery that mediate regulated exocytosis of membrane proteins are conserved across evolution.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Kioumourtzoglou, Mr Dimitrios and McCann, Miss Rebecca and Bryant, Dr Nia and Stirrat, Mrs Laura
Authors: Shewan, A. M., McCann, R. K., Lamb, C. A., Stirrat, L., Kioumourtzoglou, D., Adamson, I. S., Verma, S., James, D. E., and Bryant, N. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Journal of Cell Science
Publisher:Company of Biologists
ISSN:0021-9533
ISSN (Online):1477-9137
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