Self-assembly of the insulin-responsive vesicles creates a signaling platform for the insulin action on glucose...

In fat and skeletal muscle cells, insulin causes plasma membrane translocation of specialized insulin-responsive vesicles, or IRVs. These vesicles consist of multiple copies of Glut4, sortilin, IRAP, and LRP1 as well as several auxiliary components. Major IRV proteins have relatively long half-life inside the cell and survive multiple rounds of translocation to and from the cell surface. Here, we summarize evidence showing how the IRVs are self-assembled from pre-synthesized Glut4, sortilin, IRAP, and LRP1 after each translocation event. Furthermore, the cytoplasmic tail of sortilin binds Akt while cytoplasmic tails of IRAP and LRP1 interact with the Akt target, TBC1D4. Recruitment of signaling proteins to the IRVs may render insulin responsiveness to this compartment and thus distinguish it from other intracellular membrane vesicles.