Fab1p PtdIns(3)P 5-kinase function essential for protein sorting in the multivesicular body.
Sorting of signal-transducing cell surface receptors within multivesicular bodies (MVBs) is required for their rapid down-regulation and degradation within lysosomes. Yeast mutants defective in late stages of transport to the vacuole/lysosome accumulate MVBs. We demonstrate that the membrane glycoprotein carboxypeptidase S and the G protein-coupled receptor Ste2p are targeted into the vacuole lumen, and this process requires a subset of VPS gene products essential for normal endosome function. The PtdIns(3)P 5-kinase activity of Fab1p, which converts the product of the Vps34p PtdIns 3-kinase PtdIns(3)P into PtdIns(3,5)P2, also is required for cargo-selective sorting into the vacuole lumen. These findings demonstrate a role for phosphoinositide signaling at distinct stages of vacuolar/lysosomal protein transport and couple PtdIns(3,5)P2 synthesis to regulation of MVB sorting.
Odorizzi
G
G
Division of Cellular and Molecular Medicine and Howard Hughes Medical Institute, University of California, San Diego, School of Medicine, La Jolla 92093-0668, USA.
Babst
M
M
Emr
S D
SD
D000251:Adenosine Triphosphatases; D001692:Biological Transport; D002268:Carboxypeptidases / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport; D011992:Endosomes; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D014617:Vacuoles
D056827:Endosomal Sorting Complexes Required for Transport; D005656:Fungal Proteins; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C107528:VPS4 protein, S cerevisiae; D049452:Green Fluorescent Proteins; C095504:FAB1 protein, S cerevisiae; D017853:Phosphotransferases (Alcohol Group Acceptor); D002268:Carboxypeptidases; C019836:CPS1 protein, S cerevisiae; D000251:Adenosine Triphosphatases