Sortilin is the major 110-kDa protein in GLUT4 vesicles from adipocytes

Vesicles containing the glucose transporter GLUT4 from rat adipocytes contain a major protein of 110 kDa, We have isolated this protein, obtained the sequences of peptides, and cloned a large portion of its cDNA, This revealed that the protein is sortilin, a novel membrane protein that was cloned in another context from a human source while this work was in progress. Subcellular fractionation of rat and 3T3-L1 adipocytes, together with GLUT4 vesicle isolation, showed that sortilin was primarily located in the low density microsomes in vesicles containing GLUT4, Insulin caused a 1.7-fold increase in the amount of sortilin at the plasma membranes of 3T3-L1 adipocytes, as assessed by cell surface biotinylation, The expression of sortilin in 3T3-L1 cells occurred only upon differentiation. Previous characterization of sortilin has led to the suggestion that it functions to sort lumenal proteins from the trans Golgi. The significance of its insulin stimulated increase at the cell surface and of its expression upon differentiation will require definitive delineation of its function.