title: Endosomal sorting of GLUT4 and Gap1 is conserved between yeast and insulin-sensitive cells.
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.
authors: School of Chemistry and Molecular Bioscience, University of Queensland, St. Lucia QLD 4072, Australia. a.shewan@uq.edu.au
authors: Annette M
authors: AM
authors: Shewan
authors: Rebecca K
authors: RK
authors: McCann
authors: Christopher A
authors: CA
authors: Lamb
authors: Laura
authors: L
authors: Stirrat
authors: Dimitrios
authors: D
authors: Kioumourtzoglou
authors: Iain S
authors: IS
authors: Adamson
authors: Suzie
authors: S
authors: Verma
authors: David E
authors: DE
authors: James
authors: Nia J
authors: NJ
authors: Bryant
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D011992:Endosomes / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D015151:Immunoblotting; D051379:Mice; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000378:metabolism*
chemical_list: D020690:GTPase-Activating Proteins; D051275:Glucose Transporter Type 4
keywords: Endosomes; Protein sorting; Regulated traffic