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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenosine Triphosphatases*
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Biological Transport
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Carboxypeptidases / metabolism*
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Endosomal Sorting Complexes Required for Transport
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Endosomes
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Fungal Proteins / genetics
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Fungal Proteins / physiology
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Green Fluorescent Proteins
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Luminescent Proteins / metabolism
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Phosphotransferases (Alcohol Group Acceptor) / genetics
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Phosphotransferases (Alcohol Group Acceptor) / metabolism*
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Recombinant Fusion Proteins / metabolism
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Saccharomyces cerevisiae Proteins*
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Vacuoles
Substances
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Endosomal Sorting Complexes Required for Transport
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Fungal Proteins
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Luminescent Proteins
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Recombinant Fusion Proteins
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Saccharomyces cerevisiae Proteins
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VPS4 protein, S cerevisiae
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Green Fluorescent Proteins
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FAB1 protein, S cerevisiae
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Phosphotransferases (Alcohol Group Acceptor)
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Carboxypeptidases
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CPS1 protein, S cerevisiae
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Adenosine Triphosphatases