DOC2β: Part of the insulin-stimulated glut4 vesicle trafficking machinery in adipocytes

D. C. Thurmond, J. E. Pessin

Research output: Contribution to journalArticle

Abstract

The insulin-stimulated translocation of the glucose transporter proteins (GLUTs) to the plasma membrane in adipose and muscle tissues accounts for the majority of post-prandial glucose uptake In adipocytes, the insulin-stimulated translocation of GLl)T4-isoform vesicles requires interactions among Syntaxin 4, VAMPs, and Munc-18c proteins; these interactions are highly analogous to those of synaptic vesicle trafficking At the adipocyte plasma membrane. Syntaxin 4 and Munc-18c interact in the absence of insulin stimulation, blocking GLUT4 translocation. We proposed that additional proteins present at the plasma membrane may be required to disrupt the interaction between Munc-ISc and Syntaxin 4 and restore insulinstimulated GLUT4 translocation. Doc2β is a synaptic vesicle trafficking protein which competes with Syntaxin-1A for Munc-18a binding. We have localized Doc2β to the plasma membrane of primary rat adipocytes; subcellular fractionation showed the association of Doc2β with the plasma membrane in the absence and presence of insulin stimulation, similar to Munc-18c and Syntaxin 4. In yeast twohybrid analyses Doc2β bound to Munc-18c and to Syntaxin 4 Deletion of the first 19-51 N-terminal residues, residues 341 -479. or the final 51 C-termina] residues from Munc-18c abolished interaction with Syntaxin 4. suggesting that the entire Munc-18c protein is required for binding to Syntaxin 4. By contrast, the truncated Munc-18c proteins interacted with Doc2β. indicating that the binding requirements for Syntaxin 4 and Doc2β with Munc-18c are likely to differ. These results are consistent with the hypothesis that Doc2β may function as a regulatory component in insulin-stimulated GLUT4 translocation in adipocytes.

Original languageEnglish (US)
Pages (from-to)A1466
JournalFASEB Journal
Volume12
Issue number8
StatePublished - Dec 1 1998

    Fingerprint

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this