Title

The v-SNARE Vti1a regulates insulin-stimulated glucose transport and Acrp30 secretion in 3T3-L1 adipocytes

UMMS Affiliation

Program in Molecular Medicine

Date

9-1-2005

Document Type

Article

Subjects

3T3-L1 Cells; Adipocytes; Adiponectin; Animals; Biological Transport; Fluorescent Antibody Technique; Glucose; Glucose Transporter Type 4; Hypoglycemic Agents; Insulin; Mice; Proteomics; Qb-SNARE Proteins; RNA, Small Interfering; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; trans-Golgi Network

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Regulated exocytosis in adipocytes mediates key functions, exemplified by insulin-stimulated secretion of peptides such as adiponectin and recycling of intracellular membranes containing GLUT4 glucose transporters to the cell surface. Using a proteomics approach, the v-SNARE Vti1a (vps10p tail interacting 1a) was identified by mass spectrometry in purified GLUT4-containing membranes. Insulin treatment of 3T3-L1 adipocytes decreased the amounts of both Vti1a and GLUT4 in these membranes, confirming that Vti1a is a component of insulin-sensitive GLUT4-containing vesicles. In the basal state, endogenous Vti1a colocalizes exclusively with perinuclear GLUT4. Although Vti1a has previously been reported to be a v-SNARE localized in the trans-Golgi network, treatment with brefeldin A failed to significantly modify Vti1a or GLUT4 localization while completely dispersing Golgi and trans-Golgi network marker proteins. Furthermore, depletion of Vti1a protein in cultured adipocytes through small interfering RNA-based gene silencing significantly inhibited both adiponectin secretion and insulin-stimulated deoxyglucose uptake. Taken together, these results suggest that the v-SNARE Vti1a may regulate a step common to both GLUT4 and Acrp30 trafficking in 3T3-L1 adipocytes.

Rights and Permissions

Citation: J Biol Chem. 2005 Nov 4;280(44):36946-51. Epub 2005 Aug 29. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal Title

The Journal of biological chemistry

PubMed ID

16131485