GLUT4 ablation in mice results in redistribution of IRAP to the plasma membrane.
Glucose transporter (GLUT) 4 is the insulin responsive glucose transporter in adipose tissue, skeletal muscle, and heart. Insulin elicits increased glucose uptake by recruiting GLUT4 from a specialized intracellular storage site to the cell surface. Expression of various proteins that colocalize with GLUT4 and/or are involved in insulin-stimulated GLUT4 translocation was examined in adipocytes as well as skeletal and cardiac muscles from GLUT4 null mice. Our data demonstrate that expression of insulin-regulated aminopeptidase (IRAP) is divergently regulated in GLUT4 null tissues, e.g., upregulated 1.6-fold in GLUT4 null adipocytes and downregulated in GLUT4 null skeletal muscle (40%) and heart (60%). IRAP exhibited abnormal subcellular distribution and impaired insulin-stimulated translocation in GLUT4-deficient tissues. We propose the compartment containing IRAP and proteins normally associated with GLUT4 vesicle traffics constitutively to the cell surface in GLUT4 null adipocytes and skeletal muscle.
Jiang
H
H
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Li
J
J
Katz
E B
EB
Charron
M J
MJ
D033942:Adaptor Proteins, Vesicular Transport; D017667:Adipocytes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D000626:Aminopeptidases / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D002451:Cell Compartmentation / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000737:chemistry / Q000201:enzymology*; D002469:Cell Separation; D003433:Crosses, Genetic; D010122:Cystinyl Aminopeptidase; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000378:metabolism; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D009004:Monosaccharide Transport Proteins / Q000032:analysis / Q000172:deficiency* / Q000235:genetics; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics; D050765:Qa-SNARE Proteins; D050683:R-SNARE Proteins; D011990:Receptors, Transferrin / Q000032:analysis / Q000378:metabolism; D013347:Subcellular Fractions / Q000737:chemistry / Q000378:metabolism; D020695:rab4 GTP-Binding Proteins / Q000378:metabolism; D000099183:Sortilin
D033942:Adaptor Proteins, Vesicular Transport; D000626:Aminopeptidases; D010122:Cystinyl Aminopeptidase; D051275:Glucose Transporter Type 4; D007328:Insulin; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D050765:Qa-SNARE Proteins; D050683:R-SNARE Proteins; D011990:Receptors, Transferrin; D020695:rab4 GTP-Binding Proteins; D000099183:Sortilin; C495693:Slc2a4 protein, mouse; C105964:leucyl-cystinyl aminopeptidase