title: The first luminal loop confers insulin responsiveness to glucose transporter 4.
abstract: Glucose transporter isoform 4 (GLUT4), is the sole glucose transporter responsible for the effect of insulin on postprandial blood glucose clearance. However, the nature of the insulin sensitivity of GLUT4 remains unknown. In this study, we replaced the first luminal loop of cellugyrin, a 4-transmembrane protein that does not respond to insulin, with that of GLUT4. The chimera protein is targeted to the intracellular insulin-responsive vesicles and is translocated to the plasma membrane upon insulin stimulation. The faithful targeting of the chimera depends on the expression of the sorting receptor sortilin, which interacts with the unique amino acid residues in the first luminal loop of GLUT4. Thus the first luminal loop may confer insulin responsiveness to the GLUT4 molecule.
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Ju Youn
authors.initials: JY
authors.lastname: Kim
authors.forename: Konstantin V
authors.initials: KV
authors.lastname: Kandror
mesh_terms: D041721:3T3-L1 Cells; D033942:Adaptor Proteins, Vesicular Transport / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D051275:Glucose Transporter Type 4 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051379:Mice; D050506:Mutant Chimeric Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D062805:Synaptogyrins; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D008565:Membrane Proteins; D050506:Mutant Chimeric Proteins; D009419:Nerve Tissue Proteins; D062805:Synaptogyrins; D000099183:Sortilin