Document Detail


N-glycosylation is critical for the stability and intracellular trafficking of GLUT4 glucose transporter.
MedLine Citation:
PMID:  21757715     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The facilitative glucose transporter GLUT4 plays a key role in regulating whole-body glucose homeostasis. GLUT4 dramatically changes its distribution upon insulin stimulation, and insulin-resistant diabetes is often linked with compromised translocation of GLUT4 under insulin stimulation. To elucidate the functional significance of the sole N-glycan chain on GLUT4, wild-type GLUT4 and a GLUT4-glycosylation mutant conjugated with EGFP were stably expressed in HeLa cells. The N-glycan contributed to the overall stability of newly-synthesized GLUT4. Moreover, cell surface expression of wild-type GLUT4 in HeLa cells was elevated upon insulin treatment, while the glycosylation mutant lost the ability to respond to insulin. Subcellular distribution of the mutant was distinct from that of wild-type GLUT4, implying that the subcellular localization required for insulin-mediated translocation was impaired in the mutant protein. Interestingly, kifunensine-treated cells also lost sensitivity to insulin, suggesting the functional importance of the N-glycan structure for GLUT4 trafficking. The K(m) or turnover rate of wild-type and mutant GLUT4, however, were similar, suggesting that the N-glycan had little effect on transporter activity. These findings underscore the critical roles of the N-glycan chain in quality control as well as intracellular trafficking of the GLUT4 glucose transporter.
Authors:
Yoshimi Haga; Kumiko Ishii; Tadashi Suzuki
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-7-14
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  -     ISSN:  1083-351X     ISO Abbreviation:  -     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-7-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
RIKEN Advanced Science Institute, Japan.
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