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, obt ained the sequences of peptides, and cloned a large portion of its cDN A, This revealed that the protein is sortilin, a novel membrane protei n that was cloned in another context from a human source while this wo rk was in progress. Subcellular fractionation of rat and 3T3-L1 adipoc ytes, 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 a t the plasma membranes of 3T3-L1 adipocytes, as assessed by cell surfa ce biotinylation, The expression of sortilin in 3T3-L1 cells occurred only upon differentiation. Previous characterization of sortilin has l ed to the suggestion that it functions to sort lumenal proteins from t he trans Golgi. The significance of its insulin stimulated increase at the cell surface and of its expression upon differentiation will requ ire definitive delineation of its function.