Intracellular targeting and retention of the glucose transporter GLUT4 by the perinuclear storage compartment involves distinct carboxyl-tail motifs.
The mechanisms by which the insulin-sensitive glucose transporter, GLUT4, is targeted and retained in a storage compartment near to the Golgi complex are poorly understood. Here we report that removal of the carboxyl-terminal acidic Pro(505)AspGluAsnAsp(509) sequence prevents the storage of GLUT4 in the VAMP-2 positive compartment adjacent to the Golgi complex (GSC), and results in its targeting to GLUT4-positive vesicles and Rab7-positive late endosomes. Storage of the truncated GLUT4 in the GSC is restored by substitution of Phe for the Tyr(502) residue adjacent to Pro(505) or by treatment of cells with the tyrosine kinase inhibitor genistein. Ablation of the Leu(489)Leu(490)-based motif prevents the targeting of GLUT4delta5 to GLUT4-positive-vesicles and late endosomes as well as the retention of GLUT4delta5Phe(502 )by the GSC. These results are consisting with a model of GLUT4 transport in which the targeting of the protein from the TGN to the GSC is mediated by the Leu(489)Leu(490)-based motif and its release from the GSC involves Tyr(502 )and the adjacent carboxyl-terminal Pro(505)AspGluAsnAsp(509) sequence.
Martinez-Arca
S
S
Group of Morphogenesis and Cell Signalling, CNRS UMR 144, Institut Curie, Paris, France.
Lalioti
V S
VS
Sandoval
I V
IV
D016475:3T3 Cells; D000409:Alanine / Q000378:metabolism; D020816:Amino Acid Motifs / Q000502:physiology*; D000818:Animals; D002264:Carboxylic Acids / Q000378:metabolism*; D002451:Cell Compartmentation / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D004151:Dipeptides / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D051275:Glucose Transporter Type 4; D006056:Golgi Apparatus / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism*; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D010446:Peptide Fragments / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D010649:Phenylalanine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects; D014443:Tyrosine / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins
D002264:Carboxylic Acids; D004151:Dipeptides; D004791:Enzyme Inhibitors; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D010446:Peptide Fragments; D010455:Peptides; C495693:Slc2a4 protein, mouse; D000090802:rab7 GTP-Binding Proteins; C000716465:rab7 GTP-binding proteins, mouse; C038361:leucylleucine; D014443:Tyrosine; D010649:Phenylalanine; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D020691:rab GTP-Binding Proteins; D000409:Alanine