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Insulin controls the spatial distribution of GLUT4 on the cell surface through regulation of its postfusion dispersal

Stenkula, Karin G LU ; Lizunov, Vladimir A ; Cushman, Samuel W and Zimmerberg, Joshua (2010) In Cell Metabolism 12(3). p.9-250
Abstract

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,... (More)

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.

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author
; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
Adipocytes/cytology, Animals, Caveolins/metabolism, Cell Membrane/drug effects, Cells, Cultured, Clathrin/metabolism, Endocytosis/drug effects, Exocytosis/drug effects, Glucose Transporter Type 4/genetics, Insulin/pharmacology, Membrane Fusion/physiology, Models, Biological, Rats, Recombinant Fusion Proteins/genetics
in
Cell Metabolism
volume
12
issue
3
pages
9 - 250
publisher
Cell Press
external identifiers
  • pmid:20816091
  • scopus:77956298609
ISSN
1550-4131
DOI
10.1016/j.cmet.2010.08.005
language
English
LU publication?
no
id
e6d3f9be-96e8-4e31-bbc3-98f5762d9407
date added to LUP
2021-05-20 14:33:11
date last changed
2024-10-05 23:48:51
@article{e6d3f9be-96e8-4e31-bbc3-98f5762d9407,
  abstract     = {{<p>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.</p>}},
  author       = {{Stenkula, Karin G and Lizunov, Vladimir A and Cushman, Samuel W and Zimmerberg, Joshua}},
  issn         = {{1550-4131}},
  keywords     = {{Adipocytes/cytology; Animals; Caveolins/metabolism; Cell Membrane/drug effects; Cells, Cultured; Clathrin/metabolism; Endocytosis/drug effects; Exocytosis/drug effects; Glucose Transporter Type 4/genetics; Insulin/pharmacology; Membrane Fusion/physiology; Models, Biological; Rats; Recombinant Fusion Proteins/genetics}},
  language     = {{eng}},
  month        = {{09}},
  number       = {{3}},
  pages        = {{9--250}},
  publisher    = {{Cell Press}},
  series       = {{Cell Metabolism}},
  title        = {{Insulin controls the spatial distribution of GLUT4 on the cell surface through regulation of its postfusion dispersal}},
  url          = {{http://dx.doi.org/10.1016/j.cmet.2010.08.005}},
  doi          = {{10.1016/j.cmet.2010.08.005}},
  volume       = {{12}},
  year         = {{2010}},
}