Journal
CELL METABOLISM
Volume 12, Issue 3, Pages 250-259Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2010.08.005
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Funding
- Swedish Research Council
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Child Health and Human Development, National Institutes of Health
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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 similar to 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.
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