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Fab1p PtdIns3P 5-kinase function essenti ... ting in the multivesicular body


Fab1p PtdIns(3)P 5-kinase function essential for protein sorting in the multivesicular body.

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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, Babst M, Emr SD

Cell

1998-12-11 00:00

95

6

847-58

Adenosine Triphosphatases,Biological Transport,Carboxypeptidases,Endosomes,Fungal Proteins,Green Fluorescent Proteins,Luminescent Proteins,Phosphotransferases (Alcohol Group Acceptor),Recombinant Fusion Proteins,Saccharomyces cerevisiae Proteins,Vacuoles,Fungal Proteins,Luminescent Proteins,Recombinant Fusion Proteins,Saccharomyces cerevisiae Proteins,VPS4 protein, S cerevisiae,Green Fluorescent Proteins,FAB1 protein, S cerevisiae,Phosphotransferases (Alcohol Group Acceptor),Carboxypeptidases,carboxypeptidase S, S cerevisiae,Adenosine Triphosphatases

Division of Cellular and Molecular Medicine and Howard Hughes Medical Institute, University of California, San Diego, School of Medicine, La Jolla 92093-0668, USA

Cell

NCI CA 58689

0092-8674


S0092-8674(00)81707-9


837

True

9865702

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