Chem.283, Issue 18, 12571-12585, May 2, 2008 This Article All Versions of this Article: 283/18/12571 _most recent_ Services Google Scholar PubMed IDENTIFICATION OF AMINO ACID RESIDUES WITHIN THE C TERMINUS OF THE GLUT4 GLUCOSE TRANSPORTER THAT ARE ESSENTIAL FOR INSULIN-STIMULATED REDISTRIBUTION TO THE PLASMA MEMBRANE XIAO MEI SONG, RICHARD C.AND MIKE MUECKLER1 From the Department of Cell Biology and Physiology, Washington University School of Medicine, St.Missouri 63110 The Glut4 glucose transporter undergoesplex insulin-regulated subcellular trafficking in adipocytes.Effort has been expended in an attempt to identify targeting motifs within Glut4 that direct its subcellular trafficking, but an amino acid motif responsible for the targeting of the transporter to insulin-responsive intracellularpartments in the basal state or that is directly responsible for its insulin-stimulated redistribution to the plasma membrane has not yet been delineated.This study we define amino acid residues within the C-terminal cytoplasmic tail of Glut4 that are essential for its insulin-stimulated translocation to the plasma membrane.Residues were identified based on sequence similarity (L_XX_L_X_PDE_X_D) between cytoplasmic domains of Glut4 and the insulin-responsive aminopeptidase (IRAP).Of this putative targeting motif (IRM, insulin-responsive motif) resulted in the targeting of the bulk of the mutant Glut4 molecules to dispersed membrane vesicles that lacked detectable levels of wild-type Glut4 in either the basal or insulin-stimulated states andpletely abolished the insulin-stimulated translocation of the mutant Glut4 to the plasma membrane in 3T3L1 adipocytes.Bulk of the dispersed membrane vesicles containing the IRM mutant did not contain detectable levels of any subcellular marker tested.Fraction of the total IRM mutant was also detected in a wild-type Glut4/Syntaxin 6-containing perinuclearpartment.Mutation of the IRM sequence did not appreciably alter the subcellular trafficking of IRAP.Conclude that residues within the IRM are critical for the targeting of Glut4, but not of IRAP, to insulin-responsive intracellular membrane 1 To whom correspondence should be addressed: Dept.Cell Biology, Washington University Medical School, 660 Euclid Ave.Box 8228, St.MO 63110.Read more [mechanisms of signal transduction] regulation of interleukin-6-induced hepatic insulin resistance by mammalian target of rapamycin through the stat3-socs3 pathway
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