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 |
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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 > School of Molecular Biosciences |
Journal Name: | Journal of Cell Science |
Publisher: | Company of Biologists |
ISSN: | 0021-9533 |
ISSN (Online): | 1477-9137 |
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