Limits...
Insulin stimulates the halting, tethering, and fusion of mobile GLUT4 vesicles in rat adipose cells.

Lizunov VA, Matsumoto H, Zimmerberg J, Cushman SW, Frolov VA - J. Cell Biol. (2005)

Bottom Line: Glucose transport in adipose cells is regulated by changing the distribution of glucose transporter 4 (GLUT4) between the cell interior and the plasma membrane (PM).This slow release of GLUT4 determined the overall increase of the PM GLUT4.It is likely that the primary mechanism of insulin action in GLUT4 translocation is to stimulate tethering and fusion of trafficking vesicles to specific fusion sites in the PM.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cellular and Molecular Biophysics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.

ABSTRACT
Glucose transport in adipose cells is regulated by changing the distribution of glucose transporter 4 (GLUT4) between the cell interior and the plasma membrane (PM). Insulin shifts this distribution by augmenting the rate of exocytosis of specialized GLUT4 vesicles. We applied time-lapse total internal reflection fluorescence microscopy to dissect intermediates of this GLUT4 translocation in rat adipose cells in primary culture. Without insulin, GLUT4 vesicles rapidly moved along a microtubule network covering the entire PM, periodically stopping, most often just briefly, by loosely tethering to the PM. Insulin halted this traffic by tightly tethering vesicles to the PM where they formed clusters and slowly fused to the PM. This slow release of GLUT4 determined the overall increase of the PM GLUT4. Thus, insulin initially recruits GLUT4 sequestered in mobile vesicles near the PM. It is likely that the primary mechanism of insulin action in GLUT4 translocation is to stimulate tethering and fusion of trafficking vesicles to specific fusion sites in the PM.

Show MeSH

Related in: MedlinePlus

Hypothetical mechanism of insulin-stimulated recruitment of GLUT4 vesicles to fusion sites in the PM. In the basal state, most of the GLUT4 is in vesicles that move on microtubules along the PM passing available fusion sites. Insulin via intracellular signaling cascade stimulates tethering of GLUT4 vesicles to the first encountered fusion site; the fusing vesicles accumulate in clusters in the PM. The release of GLUT4 from fusing vesicles is restricted (see text) in ways that may be regulated.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2171949&req=5

fig6: Hypothetical mechanism of insulin-stimulated recruitment of GLUT4 vesicles to fusion sites in the PM. In the basal state, most of the GLUT4 is in vesicles that move on microtubules along the PM passing available fusion sites. Insulin via intracellular signaling cascade stimulates tethering of GLUT4 vesicles to the first encountered fusion site; the fusing vesicles accumulate in clusters in the PM. The release of GLUT4 from fusing vesicles is restricted (see text) in ways that may be regulated.

Mentions: Our kinetic model of GLUT4 recycling (see the online supplemental material) indicates that insulin augments both the probability of tethering at specific fusion sites and the subsequent priming of the vesicles leading to their fusion to the PM. In insulin-stimulated cells, the GLUT4 vesicles are expected to fuse at the first encountered fusion site as typical cargo vesicles (Schmoranzer and Simon, 2003). The probability of fusion is much less in nonstimulated cells; thus, mobile GLUT4 vesicles bypass many fusion sites, remaining on the microtubule network for a long time. Fig. 6 summarizes our model for the insulin stimulation of GLUT4 exocytosis. Upon formation, the GLUT4 vesicles move on microtubules until they fuse, like vesicles delivering constitutive post-Golgi cargo (Schmoranzer and Simon, 2003). The GLUT4 vesicles fuse to the PM at special fusion sites, with the probability of tethering and fusion being regulated by insulin.


Insulin stimulates the halting, tethering, and fusion of mobile GLUT4 vesicles in rat adipose cells.

Lizunov VA, Matsumoto H, Zimmerberg J, Cushman SW, Frolov VA - J. Cell Biol. (2005)

Hypothetical mechanism of insulin-stimulated recruitment of GLUT4 vesicles to fusion sites in the PM. In the basal state, most of the GLUT4 is in vesicles that move on microtubules along the PM passing available fusion sites. Insulin via intracellular signaling cascade stimulates tethering of GLUT4 vesicles to the first encountered fusion site; the fusing vesicles accumulate in clusters in the PM. The release of GLUT4 from fusing vesicles is restricted (see text) in ways that may be regulated.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2171949&req=5

fig6: Hypothetical mechanism of insulin-stimulated recruitment of GLUT4 vesicles to fusion sites in the PM. In the basal state, most of the GLUT4 is in vesicles that move on microtubules along the PM passing available fusion sites. Insulin via intracellular signaling cascade stimulates tethering of GLUT4 vesicles to the first encountered fusion site; the fusing vesicles accumulate in clusters in the PM. The release of GLUT4 from fusing vesicles is restricted (see text) in ways that may be regulated.
Mentions: Our kinetic model of GLUT4 recycling (see the online supplemental material) indicates that insulin augments both the probability of tethering at specific fusion sites and the subsequent priming of the vesicles leading to their fusion to the PM. In insulin-stimulated cells, the GLUT4 vesicles are expected to fuse at the first encountered fusion site as typical cargo vesicles (Schmoranzer and Simon, 2003). The probability of fusion is much less in nonstimulated cells; thus, mobile GLUT4 vesicles bypass many fusion sites, remaining on the microtubule network for a long time. Fig. 6 summarizes our model for the insulin stimulation of GLUT4 exocytosis. Upon formation, the GLUT4 vesicles move on microtubules until they fuse, like vesicles delivering constitutive post-Golgi cargo (Schmoranzer and Simon, 2003). The GLUT4 vesicles fuse to the PM at special fusion sites, with the probability of tethering and fusion being regulated by insulin.

Bottom Line: Glucose transport in adipose cells is regulated by changing the distribution of glucose transporter 4 (GLUT4) between the cell interior and the plasma membrane (PM).This slow release of GLUT4 determined the overall increase of the PM GLUT4.It is likely that the primary mechanism of insulin action in GLUT4 translocation is to stimulate tethering and fusion of trafficking vesicles to specific fusion sites in the PM.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cellular and Molecular Biophysics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.

ABSTRACT
Glucose transport in adipose cells is regulated by changing the distribution of glucose transporter 4 (GLUT4) between the cell interior and the plasma membrane (PM). Insulin shifts this distribution by augmenting the rate of exocytosis of specialized GLUT4 vesicles. We applied time-lapse total internal reflection fluorescence microscopy to dissect intermediates of this GLUT4 translocation in rat adipose cells in primary culture. Without insulin, GLUT4 vesicles rapidly moved along a microtubule network covering the entire PM, periodically stopping, most often just briefly, by loosely tethering to the PM. Insulin halted this traffic by tightly tethering vesicles to the PM where they formed clusters and slowly fused to the PM. This slow release of GLUT4 determined the overall increase of the PM GLUT4. Thus, insulin initially recruits GLUT4 sequestered in mobile vesicles near the PM. It is likely that the primary mechanism of insulin action in GLUT4 translocation is to stimulate tethering and fusion of trafficking vesicles to specific fusion sites in the PM.

Show MeSH
Related in: MedlinePlus