Mechanism and regulation of GLUT-4 vesicle fusion in muscle and fat cells.
Twenty years ago it was shown that recruitment of glucose transporters from an internal membrane compartment to the plasma membrane led to increased glucose uptake into fat and muscle cells stimulated by insulin. The final step of this process is the fusion of glucose transporter 4 (GLUT-4)-containing vesicles with the plasma membrane. The identification of a neuronal soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex as a requirement for synaptic vesicle-plasma membrane fusion led to the search for homologous complexes outside the nervous system. Indeed, isoforms of the neuronal SNAREs were identified in muscle and fat cells and were shown to be required for GLUT-4 incorporation into the cell membrane. In addition, proteins that bind to nonneuronal SNAREs were cloned and proposed to regulate vesicle fusion. We have summarized the molecular mechanisms leading to membrane fusion in nonneuronal systems, focusing on the role of SNAREs and accessory proteins (Munc18c, synip, Rab4, and VAP-33) in incorporation of GLUT-4 into the plasma membrane. Potential modes of regulation of this process are discussed, including SNARE phosphorylation and interaction with the cytoskeleton.
Foster
L J
LJ
Cell Biology Programme, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
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D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism; D002451:Cell Compartmentation / Q000502:physiology; D003599:Cytoskeleton / Q000378:metabolism; D051275:Glucose Transporter Type 4; D006801:Humans; D008561:Membrane Fusion / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D009132:Muscles / Q000166:cytology / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D015388:Organelles / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D050765:Qa-SNARE Proteins; D050683:R-SNARE Proteins; D051381:Rats; D050600:SNARE Proteins; D050825:Synaptosomal-Associated Protein 25; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D051275:Glucose Transporter Type 4; D008565:Membrane Proteins; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D050765:Qa-SNARE Proteins; D050683:R-SNARE Proteins; C495692:SLC2A4 protein, human; C494208:SNAP25 protein, human; D050600:SNARE Proteins; C495694:Slc2a4 protein, rat; C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; D033921:Vesicular Transport Proteins