Biogenesis and regulation of insulin-responsive vesicles containing GLUT4.
Insulin regulates the trafficking of GLUT4 glucose transporters in fat and muscle cells. In unstimulated cells, GLUT4 is sequestered intracellularly in small, insulin-responsive vesicles. Insulin stimulates the translocation of these vesicles to the cell surface, inserting the transporters into the plasma membrane to enhance glucose uptake. Formation of the insulin-responsive vesicles requires multiple interactions among GLUT4, IRAP, LRP1, and sortilin, as well as recruitment of GGA and ACAP1 adaptors and clathrin. Once formed, the vesicles are retained within unstimulated cells by the action of TUG, Ubc9, and other proteins. In addition to acting at other steps in vesicle recycling, insulin releases this retention mechanism to promote the translocation and fusion of the vesicles at the cell surface.
Bogan
Jonathan S
JS
Section of Endocrinology and Metabolism, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA. jonathan.bogan@yale.edu
Kandror
Konstantin V
KV
D000818:Animals; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D022161:Transport Vesicles / Q000187:drug effects* / Q000378:metabolism*
D051275:Glucose Transporter Type 4; D007328:Insulin