Insulin-stimulated plasma membrane fusion of Glut4 glucose transporter-containing vesicles is regulated by phospholipase D1

Ping Huang, Yelena M. Altshuller, June Chunqiu Hou, Jeffrey E. Pessin, Michael A. Frohman

Research output: Contribution to journalArticle

108 Scopus citations

Abstract

Insulin stimulates glucose uptake in fat and muscle by mobilizing Glut4 glucose transporters from intracellular membrane storage sites to the plasma membrane. This process requires the trafficking of Glut4-containing vesicles toward the cell periphery, docking at exocytic sites, and plasma membrane fusion. We show here that phospholipase D (PLD) production of the lipid phosphatidic acid (PA) is a key event in the fusion process. PLD1 is found on Glut4-containing vesicles, is activated by insulin signaling, and traffics with Glut4 to exocytic sites. Increasing PLD1 activity facilitates glucose uptake, whereas decreasing PLD1 activity is inhibitory. Diminished PA production does not substantially hinder trafficking of the vesicles or their docking at the plasma membrane, but it does impede fusion-mediated extracellular exposure of the transporter. The fusion block caused by RNA interference-mediated PLD1 deficiency is rescued by exogenous provision of a lipid that promotes fusion pore formation and expansion, suggesting that the step regulated by PA is late in the process of vesicle fusion.

Original languageEnglish (US)
Pages (from-to)2614-2623
Number of pages10
JournalMolecular biology of the cell
Volume16
Issue number6
DOIs
StatePublished - Jun 9 2005
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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