Endosomal sorting of GLUT4 and Gap1 is conserved between yeast and insulin-sensitive cells
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, gamma-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.
|ISBN||1477-9137 (Electronic) 0021-9533 (Linking)|
|Authors||Shewan, A. M. ; McCann, R. K. ; Lamb, C. A. ; Stirrat, L. ; Kioumourtzoglou, D. ; Adamson, I. S.; Verma, S. James, D. E. Bryant, N. J.;|
|Publisher Name||JOURNAL OF CELL SCIENCE|
|Published Issue||Pt 7|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/pubmed/23424197|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/11977|