A Role for the CHC22 clathrin heavy-chain isoform in human glucose metabolism

Stéphane Vassilopoulos, Christopher Esk, Sachiko Hoshino, Birgit H. Funke, Chih Ying Chen, Alex M. Plocik, Woodring E. Wright, Raju Kucherlapati, Frances M. Brodsky

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77 Scopus citations

Abstract

Intracellular trafficking of the glucose transporter GLUT4 from storage compartments to the plasma membrane is triggered in muscle and fat during the body's response to insulin. Clathrin is involved in intracellular trafficking, and in humans, the clathrin heavy-chain isoform CHC22 is highly expressed in skeletal muscle. We found a role for CHC22 in the formation of insulin-responsive GLUT4 compartments in human muscle and adipocytes. CHC22 also associated with expanded GLUT4 compartments in muscle from type 2 diabetic patients. Tissue-specific introduction of CHC22 in mice, which have only a pseudogene for this protein, caused aberrant localization of GLUT4 transport pathway components in their muscle, as well as features of diabetes. Thus, CHC22-dependent membrane trafficking constitutes a species-restricted pathway in human muscle and fat with potential implications for type 2 diabetes.

Original languageEnglish (US)
Pages (from-to)1192-1196
Number of pages5
JournalScience
Volume324
Issue number5931
DOIs
StatePublished - May 29 2009

ASJC Scopus subject areas

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    Vassilopoulos, S., Esk, C., Hoshino, S., Funke, B. H., Chen, C. Y., Plocik, A. M., Wright, W. E., Kucherlapati, R., & Brodsky, F. M. (2009). A Role for the CHC22 clathrin heavy-chain isoform in human glucose metabolism. Science, 324(5931), 1192-1196. https://doi.org/10.1126/science.1171529