HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 283, Issue 18, 12571-12585, May 2, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: 283/18/12571    most recent M800838200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Song, X. M. Articles by Mueckler, M. Search for Related Content PubMed PubMed Citation Articles by Song, X. M. Articles by Mueckler, M. Social Bookmarking                      What's this?

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^*

From the Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110

The Glut4 glucose transporter undergoes complex insulin-regulated subcellular trafficking in adipocytes. Much 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 intracellular compartments in the basal state or that is directly responsible for its insulin-stimulated redistribution to the plasma membrane has not yet been delineated. In 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. The residues were identified based on sequence similarity (LXXLXPDEXD) between cytoplasmic domains of Glut4 and the insulin-responsive aminopeptidase (IRAP). Alteration 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 and completely abolished the insulin-stimulated translocation of the mutant Glut4 to the plasma membrane in 3T3L1 adipocytes. The bulk of the dispersed membrane vesicles containing the IRM mutant did not contain detectable levels of any subcellular marker tested. A fraction of the total IRM mutant was also detected in a wild-type Glut4/Syntaxin 6-containing perinuclear compartment. Interestingly, mutation of the IRM sequence did not appreciably alter the subcellular trafficking of IRAP. We conclude that residues within the IRM are critical for the targeting of Glut4, but not of IRAP, to insulin-responsive intracellular membrane compartments in 3T3-L1 adipocytes.

Received for publication, January 31, 2008

^* This work was supported by the American Diabetes Association and by National Institutes of Health Grants R01 DK067229 and R01 DK043695. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Dept. of Cell Biology, Washington University Medical School, 660 Euclid Ave., Campus Box 8228, St. Louis, MO 63110. Tel.: 314-362-4160; Fax: 314-362-7463; E-mail: mmueckler{at}wustl.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				V. Blot and T. E. McGraw Molecular Mechanisms Controlling GLUT4 Intracellular Retention Mol. Biol. Cell, August 1, 2008; 19(8): 3477 - 3487. [Abstract] [Full Text] [PDF]