GLUT4 recycles via a trans-Golgi network (TGN) subdomain enriched in Syntaxins 6 and 16 but not TGN38:: Involvement of an acidic targeting motif

被引:171
作者
Shewan, AM
van Dam, EM
Martin, S
Luen, TB
Hong, WJ
Bryant, NJ
James, DE [1 ]
机构
[1] St Vincents Hosp, Garvan Inst Med Res, Darlinghurst, NSW 2010, Australia
[2] Natl Univ Singapore, Inst Mol & Cell Biol, Membrane Biol Lab, Singapore 117609, Singapore
[3] Univ Queensland, Dept Physiol & Pharmacol, Brisbane, Qld 4072, Australia
[4] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia
关键词
D O I
10.1091/mbc.E02-06-0315
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Insulin stimulates glucose transport in fat and muscle cells by triggering exocytosis of the glucose transporter GLUT4. To define the intracellular trafficking of GLUT4, we have studied the internalization of an epitope-tagged version of GLUT4 from the cell surface. GLUT4 rapidly traversed the endosomal system en route to a perinuclear location. This perinuclear GLUT4 compartment did not colocalize with endosomal markers (endosomal antigen I protein, transferrin) or TGN38, but showed significant overlap with the TGN target (t)-soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) Syntaxins 6 and 16. These results were confirmed by vesicle immunoisolation. Consistent with a role for Syntaxins 6 and 16 in GLUT4 trafficking we found that their expression was up-regulated significantly during adipocyte differentiation and insulin stimulated their movement to the cell surface. GLUT4 trafficking between endosomes and trans-Golgi network was regulated via an acidic targeting motif in the carboxy terminus of GLUT4, because a mutant lacking this motif was retained in endosomes. We conclude that GLUT4 is rapidly transported from the cell surface to a subdomain of the trans-Golgi network that is enriched in the t-SNAREs Syntaxins 6 and 16 and that an acidic targeting motif in the C-terminal tail of GLUT4 plays an important role in this process.
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页码:973 / 986
页数:14
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