Alternative routes to the cell surface underpin insulin-regulated membrane trafficking of GLUT4

Dimitrios Kioumourtzoglou, Paul R. Pryor, Gwyn W. Gould, Nia J. Bryant

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Abstract

Insulin-stimulated delivery of glucose transporters (GLUT4, also known as SLC2A4) from specialized intracellular GLUT4 storage vesicles (GSVs) to the surface of fat and muscle cells is central to whole-body glucose regulation. This translocation and subsequent internalization of GLUT4 back into intracellular stores transits through numerous small membrane-bound compartments (internal GLUT4- containing vesicles; IGVs) including GSVs, but the function of these different compartments is not clear. Cellugyrin (also known as synaptogyrin-2) and sortilin define distinct populations of IGV; sortilinpositive IGVs represent GSVs, but the function of cellugyrincontaining IGVs is unknown. Here, we demonstrate a role for cellugyrin in intracellular sequestration of GLUT4 in HeLa cells and have used a proximity ligation assay to follow changes in pairwise associations between cellugyrin, sortilin, GLUT4 and membrane trafficking machinery following insulin-stimulation of 3T3-L1 adipoctyes. Our data suggest that insulin stimulates traffic from cellugyrin-containing to sortilin-containing membranes, and that cellugyrin-containing IGVs provide an insulin-sensitive reservoir to replenish GSVs following insulin-stimulated exocytosis of GLUT4. Furthermore, our data support the existence of a pathway from cellugyrin-containing membranes to the surface of 3T3-L1 adipocytes that bypasses GSVs under basal conditions, and that insulin diverts traffic away from this into GSVs.

Original languageEnglish
Pages (from-to)2423-2429
Number of pages7
JournalJournal of Cell Science
Volume128
Issue number14
Early online date15 Jul 2015
DOIs
Publication statusE-pub ahead of print - 15 Jul 2015

Keywords

  • endosome
  • gyrin
  • membrane traffic

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