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LST8 negatively regulates amino acid biosynthesis as a component of the TOR pathway
LST8, a Saccharomyces cerevisiae gene encoding a 34-kD WD-repeat protein, was identified by mutations that caused defects in sorting Gap1p to the plasma membrane. Here, we report that the Gap1p sorting defect in the lst8-1 mutant results from derepression of Rtg1/3p activity and the subsequent accum...
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2003
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172900/ https://www.ncbi.nlm.nih.gov/pubmed/12719473 http://dx.doi.org/10.1083/jcb.200210141 |
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author | Chen, Esther J. Kaiser, Chris A. |
author_facet | Chen, Esther J. Kaiser, Chris A. |
author_sort | Chen, Esther J. |
collection | PubMed |
description | LST8, a Saccharomyces cerevisiae gene encoding a 34-kD WD-repeat protein, was identified by mutations that caused defects in sorting Gap1p to the plasma membrane. Here, we report that the Gap1p sorting defect in the lst8-1 mutant results from derepression of Rtg1/3p activity and the subsequent accumulation of high levels of intracellular amino acids, which signal Gap1p sorting to the vacuole. To identify the essential function of Lst8p, we isolated lst8 mutants that are temperature-sensitive for growth. These mutants show hypersensitivity to rapamycin and derepressed Gln3p activity like cells with compromised TOR pathway activity. Like tor2 mutants, lst8 mutants also have cell wall integrity defects. Confirming a role for Lst8p in the TOR pathway, we find that Lst8p associates with both Tor1p and Tor2p and is a peripheral membrane protein that localizes to endosomal or Golgi membranes and cofractionates with Tor1p. Further, we show that a sublethal concentration of rapamycin mimics the Gap1p sorting defect of an lst8 mutant. Finally, the different effects of lst8 alleles on the activation of either the Rtg1/3p or Gln3p transcription factors reveal that these two pathways constitute distinct, genetically separable outputs of the Tor–Lst8 regulatory complex. |
format | Text |
id | pubmed-2172900 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2003 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21729002008-05-01 LST8 negatively regulates amino acid biosynthesis as a component of the TOR pathway Chen, Esther J. Kaiser, Chris A. J Cell Biol Article LST8, a Saccharomyces cerevisiae gene encoding a 34-kD WD-repeat protein, was identified by mutations that caused defects in sorting Gap1p to the plasma membrane. Here, we report that the Gap1p sorting defect in the lst8-1 mutant results from derepression of Rtg1/3p activity and the subsequent accumulation of high levels of intracellular amino acids, which signal Gap1p sorting to the vacuole. To identify the essential function of Lst8p, we isolated lst8 mutants that are temperature-sensitive for growth. These mutants show hypersensitivity to rapamycin and derepressed Gln3p activity like cells with compromised TOR pathway activity. Like tor2 mutants, lst8 mutants also have cell wall integrity defects. Confirming a role for Lst8p in the TOR pathway, we find that Lst8p associates with both Tor1p and Tor2p and is a peripheral membrane protein that localizes to endosomal or Golgi membranes and cofractionates with Tor1p. Further, we show that a sublethal concentration of rapamycin mimics the Gap1p sorting defect of an lst8 mutant. Finally, the different effects of lst8 alleles on the activation of either the Rtg1/3p or Gln3p transcription factors reveal that these two pathways constitute distinct, genetically separable outputs of the Tor–Lst8 regulatory complex. The Rockefeller University Press 2003-04-28 /pmc/articles/PMC2172900/ /pubmed/12719473 http://dx.doi.org/10.1083/jcb.200210141 Text en Copyright © 2003, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Chen, Esther J. Kaiser, Chris A. LST8 negatively regulates amino acid biosynthesis as a component of the TOR pathway |
title |
LST8 negatively regulates amino acid biosynthesis as a component of the TOR pathway |
title_full |
LST8 negatively regulates amino acid biosynthesis as a component of the TOR pathway |
title_fullStr |
LST8 negatively regulates amino acid biosynthesis as a component of the TOR pathway |
title_full_unstemmed |
LST8 negatively regulates amino acid biosynthesis as a component of the TOR pathway |
title_short |
LST8 negatively regulates amino acid biosynthesis as a component of the TOR pathway |
title_sort | lst8 negatively regulates amino acid biosynthesis as a component of the tor pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172900/ https://www.ncbi.nlm.nih.gov/pubmed/12719473 http://dx.doi.org/10.1083/jcb.200210141 |
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