Sortilin is essential and sufficient for the formation of Glut4 storage vesicles in 3T3-L1 adipocytes.
Impaired translocation of the glucose transporter isoform 4 (Glut4) to the plasma membrane in fat and skeletal muscle cells may represent a primary defect in the development of type 2 diabetes mellitus. Glut4 is localized in specialized storage vesicles (GSVs), the biological nature and biogenesis of which are not known. Here, we report that GSVs are formed in differentiating 3T3-L1 adipocytes upon induction of sortilin on day 2 of differentiation. Forced expression of Glut4 prior to induction of sortilin leads to rapid degradation of the transporter, whereas overexpression of sortilin increases formation of GSVs and stimulates insulin-regulated glucose uptake. Knockdown of sortilin decreases both formation of GSVs and insulin-regulated glucose uptake. Finally, we have reconstituted functional GSVs in undifferentiated cells by double transfection of Glut4 and sortilin. Thus, sortilin is not only essential, but also sufficient for biogenesis of GSVs and acquisition of insulin responsiveness in adipose cells.
Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Jun
J
Shi
Konstantin V
KV
Kandror
D041721:3T3-L1 Cells; D033942:Adaptor Proteins, Vesicular Transport; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D022162:Cytoplasmic Vesicles / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D000099183:Sortilin
D033942:Adaptor Proteins, Vesicular Transport; D005947:Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D000099183:Sortilin; C495693:Slc2a4 protein, mouse