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Cell. 1998 Dec 11;95(6):847-58.

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

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  • 1Division of Cellular and Molecular Medicine and Howard Hughes Medical Institute, University of California, San Diego, School of Medicine, La Jolla 92093-0668, USA.

Abstract

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.

PMID:
9865702
[PubMed - indexed for MEDLINE]
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