Insulin Stimulates Phosphatidylinositol 3-Phosphate Production via the Activation of Rab5.

Insulin Stimulates Phosphatidylinositol 3-Phosphate Production via the Activation of Rab5. Research Abstract Details 

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Insulin Stimulates Phosphatidylinositol 3-Phosphate Production via the Activation of Rab5. Abstract Text:

Phosphatidylinositol 3-phosphate (PI(3)P) plays an important role in insulin-stimulated glucose uptake. Insulin promotes the production of PI(3)P at the plasma membrane by a process dependent on TC10 activation. Here, we report that insulin-stimulated PI(3)P production requires the activation of Rab5, a small GTPase that plays a critical role in phosphoinositide synthesis and turnover. This activation occurs at the plasma membrane and is downstream of TC10. TC10 stimulates Rab5 activity via the recruitment of GAPEX-5, a VPS9 domain-containing guanyl nucleotide exchange factor that forms a complex with TC10. Although overexpression of plasma membrane-localized GAPEX-5 or constitutively active Rab5 promotes PI(3)P formation, knockdown of GAPEX-5 or overexpression of a dominant negative Rab5 mutant blocks the effects of insulin or TC10 on this process. Concomitant with its effect on PI(3)P levels, the knockdown of GAPEX-5 blocks insulin-stimulated Glut4 translocation and glucose uptake. Together, these studies suggest that the TC10/GAPEX-5/Rab5 axis mediates insulin-stimulated production of PI(3)P, which regulates trafficking of Glut4 vesicles.

Insulin Stimulates Phosphatidylinositol 3-Phosphate Production via the Activation of Rab5. Publishing Authors By Initials

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Insulin Stimulates Phosphatidylinositol 3-Phosphate Production via the Activation of Rab5. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Molecular biology of the cell

VOLUME: 19

Page Numbers: 2718-28

Journal Abbreviation: Mol. Biol. Cell

ISSN: 1059-1524

DAY: 23

MONTH: 04

YEAR: 2008

Insulin Stimulates Phosphatidylinositol 3-Phosphate Production via the Activation of Rab5. Information

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LANGUAGE: eng

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AFFILIATION: *Life Sciences Institute, Departments of Internal Medicine and Molecular and Integrative Physiology and Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109.

Country: United States

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MEDLINETA: Mol Biol Cell

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