Biogenesis of insulin-responsive GLUT4 vesicles is independent of brefeldin A-sensitive trafficking |
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Authors: | Martin S Ramm G Lyttle C T Meerloo T Stoorvogel W James D E |
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Institution: | Centre for Molecular and Cellular Biology and Department of Physiology and Pharmacology, University of Queensland, St. Lucia, Brisbane, QLD 4072, Australia;Department of Cell Biology, Medical School, University of Utrecht, 3584CX Utrecht, The Netherlands |
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Abstract: | Insulin stimulates translocation of GLUT4 from an intracellular compartment to the plasma membrane in adipocytes. As a significant amount of GLUT4 is localised to the TGN, independently of the biosynthetic pathway, one possibility is that trafficking via the TGN is important in either intracellular sequestration or insulin-dependent movement to the cell surface. In this study we have used immuno-electron microscopy to show that GLUT4 is localised to AP-1 vesicles in the TGN region in 3T3-L1 adipocytes. To dissect the role of this trafficking pathway we used brefeldin A (BFA) to disrupt AP-1 association with membranes. Despite a reorganisation of GLUT4 compartments following BFA treatment, the intracellular sequestration of GLUT4, and its insulin-dependent movement to the cell surface, was unaffected. BFA increased the half time of reversal of insulin-stimulated glucose transport from 17 to 30 min but did not prevent complete reversal. Furthermore, following reversal re-stimulation of glucose transport activity by insulin was not compromised. We conclude that under basal conditions GLUT4 cycles between the TGN and endosomes via the AP-1 pathway. However, neither this pathway, nor any other BFA-sensitive pathway, appears to play a major role in insulin-dependent recruitment of GLUT4 to the cell surface. |
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Keywords: | AP-1 BFA GLUT4 insulin MPR TGN |
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