Molecular Biology of the Cell

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

MBC in Press, published online ahead of print June 11, 2008
Mol. Biol. Cell 10.1091/mbc.E08-03-0236

A more recent version of this article appeared on August 1, 2008
This Article
Right arrow Full Text (PDF)
Right arrow Supplemental Materials
Right arrow All Versions of this Article:
E08-03-0236v1
19/8/3477    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Blot, V.
Right arrow Articles by McGraw, T. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Blot, V.
Right arrow Articles by McGraw, T. E.

Submitted on March 5, 2008
Revised on May 12, 2008
Accepted on June 4, 2008

Molecular Mechanisms Controlling GLUT4 Intracellular Retention

Vincent Blot and Timothy E. McGraw

Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065

Monitoring Editor: Sandra Lemmon

In basal adipocytes GLUT4 is sequestered intracellularly by an insulin-reversible retention mechanism. Here we analyze the roles of three GLUT4 trafficking motifs (FQQI, TELEY and LL), providing molecular links between insulin signaling, cellular trafficking machinery and the motifs in the specialized trafficking of GLUT4. Our results support a GLUT4 retention model that involves two linked intracellular cycles: one between endosomes and a retention compartment, and the other between endosomes and specialized GLUT4 transport vesicles. Targeting of GLUT4 to the former is dependent on the FQQI motif and its targeting to the latter is depend on the TELEY motif. These two motifs act independently in retention, with the TELEY-dependent step being under the control of signaling downstream of the AS160 rab GAP. Segregation of GLUT4 from endosomes, although positively correlated with the degree of basal retention, does not completely account for GLUT4 retention or insulin-responsiveness. Mutation of the LL motif slows return to basal intracellular retention following insulin withdrawal. Knockdown of AP-1 clathrin adaptin causes a delay in the return to intracellular retention following insulin withdrawal. The effects of mutating the LL motif and knockdown of AP-1 were not additive; establishing that AP-1 regulation of GLUT4 trafficking requires the LL motif.

Address correspondence to: Timothy E. McGraw (temcgraw{at}med.cornell.edu)






Home Help [Feedback] [For Subscribers] [Archive] [Search] --
Copyright © 2008 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.