Insulin Controls the Spatial Distribution of GLUT4 on the Cell Surface through Regulation of Its Postfusion Dispersal
| Autor: | Samuel W. Cushman, Karin G. Stenkula, Joshua Zimmerberg, Vladimir A. Lizunov |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
endocrine system diseases
Physiology Recombinant Fusion Proteins media_common.quotation_subject HUMDISEASE Endocytosis Caveolins Membrane Fusion Models Biological Clathrin Article Exocytosis Cell membrane Adipocytes medicine Animals Insulin Internalization Molecular Biology Cells Cultured media_common Glucose Transporter Type 4 biology Cell Membrane Lipid bilayer fusion nutritional and metabolic diseases Munc-18 Cell Biology musculoskeletal system Rats Cell biology medicine.anatomical_structure SIGNALING biology.protein GLUT4 hormones hormone substitutes and hormone antagonists |
| Zdroj: | Cell Metabolism. 12(3):250-259 |
| ISSN: | 1550-4131 |
| DOI: | 10.1016/j.cmet.2010.08.005 |
| Popis: | While the glucose transporter-4 (GLUT4) is fundamental to insulin-regulated glucose metabolism, its dynamic spatial organization in the plasma membrane (PM) is unclear. Here, using multicolor TIRF microscopy in transfected adipose cells, we demonstrate that insulin regulates not only the exocytosis of GLUT4 storage vesicles but also PM distribution of GLUT4 itself. In the basal state, domains (clusters) of GLUT4 molecules in PM are created by an exocytosis that retains GLUT4 at the fusion site. Surprisingly, when insulin induces a burst of GLUT4 exocytosis, it does not merely accelerate this basal exocytosis but rather stimulates approximately 60-fold another mode of exocytosis that disperses GLUT4 into PM. In contradistinction, internalization of most GLUT4, regardless of insulin, occurs from pre-existing clusters via the subsequent recruitment of clathrin. The data fit a new kinetic model that features multifunctional clusters as intermediates of exocytosis and endocytosis. |
| Databáze: | OpenAIRE |
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