CLONING AND CHARACTERIZATION OF A NOVEL INSULIN-REGULATED MEMBRANE AMINOPEPTIDASE FROM GLUT4 VESICLES

The insulin-regulated glucose transporter isotype GluT4 expressed only in muscle and adipose cells is sequestered in a specific secretory ve sicle, These vesicles harbor another major protein, referred to as vp1 65 (for vesicle protein of 165 kDa), that like GluT4 redistributes to the plasma membrane in response to insulin, We describe here the cloni ng of vp165 and show that it is a novel member of the family of zinc-d ependent membrane aminopeptidases, with the typical large extracellula r catalytic domain and single transmembrane do main but with a unique extended cytoplasmic domain, The latter contains two dileucine motifs, which may be critical for the specific trafficking of vp165, since th is has been shown to be the case for this motif in GluT4, However, the tissue distribution of vp165 is much wider than that of GluT4; conseq uently, vp165 may also function in processes unrelated to insulin acti on and may serve as a ubiquitous marker for a specialized regulated se cretory vesicle.