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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adipocytes / cytology
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Adipocytes / metabolism*
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Adipocytes / ultrastructure
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Animals
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Blood Glucose / metabolism
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Cell Differentiation
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Cell Line
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Cell Membrane / metabolism
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Clathrin / chemistry
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Clathrin / metabolism*
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Clathrin Heavy Chains
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Clathrin-Coated Vesicles / metabolism*
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Diabetes Mellitus, Type 2 / metabolism*
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Glucose / metabolism*
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Glucose Transporter Type 4 / metabolism*
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Humans
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Insulin / blood
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Insulin / pharmacology
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Mice
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Mice, Transgenic
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Muscle Fibers, Skeletal / metabolism
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Muscle, Skeletal / metabolism*
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Muscle, Skeletal / ultrastructure
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Myoblasts / cytology
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Myoblasts / metabolism
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Myoblasts / ultrastructure
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Protein Isoforms / chemistry
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Protein Isoforms / metabolism
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Protein Transport
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Signal Transduction
Substances
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Blood Glucose
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CLTCL1 protein, human
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Clathrin
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Glucose Transporter Type 4
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Insulin
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Protein Isoforms
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SLC2A4 protein, human
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Clathrin Heavy Chains
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Glucose