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

被引:550
作者
Odorizzi, G
Babst, M
Emr, SD [1 ]
机构
[1] Univ Calif San Diego, Sch Med, Div Cellular & Mol Med, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Sch Med, Howard Hughes Med Inst, La Jolla, CA 92093 USA
关键词
D O I
10.1016/S0092-8674(00)81707-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 B-kinase activity of Fab1p, which converts the product of the Vps34p PtdIns 3-kinase PtdIns(3)P into PtdIns(3,5)P-2, 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)P-2 synthesis to regulation of MVB sorting.
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页码:847 / 858
页数:12
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