Cloning and characterization of a novel insulin-regulated membrane aminopeptidase from Glut4 vesicles.
The insulin-regulated glucose transporter isotype GlutT4 expressed only in muscle and adipose cells is sequestered in a specific secretory vesicle. These vesicles harbor another major protein, referred to as vp165 (for vesicle protein of 165 kDa), that like GluT4 redistributes to the plasma membrane in response to insulin. We describe here the cloning of vp165 and show that it is a novel member of the family of zinc-dependent membrane aminopeptidases, with the typical large extracellular catalytic domain and single transmembrane domain but with a unique extended cytoplasmic domain. The latter contains two dileucine motifs, which may be critical for the specific trafficking of vp165, since this 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; consequently, vp165 may also function in processes unrelated to insulin action and may serve as a ubiquitous marker for a specialized regulated secretory vesicle.
Keller
S R
SR
Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755-3844, USA.
Scott
H M
HM
Mastick
C C
CC
Aebersold
R
R
Lienhard
G E
GE
D000273:Adipose Tissue / Q000201:enzymology / Q000378:metabolism; D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002462:Cell Membrane / Q000201:enzymology; D003001:Cloning, Molecular; D010122:Cystinyl Aminopeptidase; D003594:Cytoplasmic Granules / Q000201:enzymology / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D051275:Glucose Transporter Type 4; D006801:Humans; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014018:Tissue Distribution
D017931:DNA Primers; D018076:DNA, Complementary; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; C495692:SLC2A4 protein, human; C495694:Slc2a4 protein, rat; D000626:Aminopeptidases; D010122:Cystinyl Aminopeptidase; C105964:leucyl-cystinyl aminopeptidase