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Vacuole-mediated selective regulation of TORC1-Sch9 signaling following oxidative stress

Target of rapamycin complex 1 (TORC1) is a central cellular signaling coordinator that allows eukaryotic cells to adapt to the environment. In the budding yeast, Saccharomyces cerevisiae, TORC1 senses nitrogen and various stressors and modulates proteosynthesis, nitrogen uptake and metabolism, stres...

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Autores principales: Takeda, Eigo, Jin, Natsuko, Itakura, Eisuke, Kira, Shintaro, Kamada, Yoshiaki, Weisman, Lois S., Noda, Takeshi, Matsuura, Akira
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6014174/
https://www.ncbi.nlm.nih.gov/pubmed/29237820
http://dx.doi.org/10.1091/mbc.E17-09-0553
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author Takeda, Eigo
Jin, Natsuko
Itakura, Eisuke
Kira, Shintaro
Kamada, Yoshiaki
Weisman, Lois S.
Noda, Takeshi
Matsuura, Akira
author_facet Takeda, Eigo
Jin, Natsuko
Itakura, Eisuke
Kira, Shintaro
Kamada, Yoshiaki
Weisman, Lois S.
Noda, Takeshi
Matsuura, Akira
author_sort Takeda, Eigo
collection PubMed
description Target of rapamycin complex 1 (TORC1) is a central cellular signaling coordinator that allows eukaryotic cells to adapt to the environment. In the budding yeast, Saccharomyces cerevisiae, TORC1 senses nitrogen and various stressors and modulates proteosynthesis, nitrogen uptake and metabolism, stress responses, and autophagy. There is some indication that TORC1 may regulate these downstream pathways individually. However, the potential mechanisms for such differential regulation are unknown. Here we show that the serine/threonine protein kinase Sch9 branch of TORC1 signaling depends specifically on the integrity of the vacuolar membrane, and this dependency originates in changes in Sch9 localization reflected by phosphatidylinositol 3,5-bisphosphate. Moreover, oxidative stress induces the delocalization of Sch9 from vacuoles, contributing to the persistent inhibition of the Sch9 branch after stress. Thus, our results establish that regulation of the vacuolar localization of Sch9 serves as a selective switch for the Sch9 branch in divergent TORC1 signaling. We propose that the Sch9 branch integrates the intrinsic activity of TORC1 kinase and vacuolar status, which is monitored by the phospholipids of the vacuolar membrane, into the regulation of macromolecular synthesis.
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spelling pubmed-60141742018-06-22 Vacuole-mediated selective regulation of TORC1-Sch9 signaling following oxidative stress Takeda, Eigo Jin, Natsuko Itakura, Eisuke Kira, Shintaro Kamada, Yoshiaki Weisman, Lois S. Noda, Takeshi Matsuura, Akira Mol Biol Cell Articles Target of rapamycin complex 1 (TORC1) is a central cellular signaling coordinator that allows eukaryotic cells to adapt to the environment. In the budding yeast, Saccharomyces cerevisiae, TORC1 senses nitrogen and various stressors and modulates proteosynthesis, nitrogen uptake and metabolism, stress responses, and autophagy. There is some indication that TORC1 may regulate these downstream pathways individually. However, the potential mechanisms for such differential regulation are unknown. Here we show that the serine/threonine protein kinase Sch9 branch of TORC1 signaling depends specifically on the integrity of the vacuolar membrane, and this dependency originates in changes in Sch9 localization reflected by phosphatidylinositol 3,5-bisphosphate. Moreover, oxidative stress induces the delocalization of Sch9 from vacuoles, contributing to the persistent inhibition of the Sch9 branch after stress. Thus, our results establish that regulation of the vacuolar localization of Sch9 serves as a selective switch for the Sch9 branch in divergent TORC1 signaling. We propose that the Sch9 branch integrates the intrinsic activity of TORC1 kinase and vacuolar status, which is monitored by the phospholipids of the vacuolar membrane, into the regulation of macromolecular synthesis. The American Society for Cell Biology 2018-02-15 /pmc/articles/PMC6014174/ /pubmed/29237820 http://dx.doi.org/10.1091/mbc.E17-09-0553 Text en © 2018 Takeda et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0/ This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.
spellingShingle Articles
Takeda, Eigo
Jin, Natsuko
Itakura, Eisuke
Kira, Shintaro
Kamada, Yoshiaki
Weisman, Lois S.
Noda, Takeshi
Matsuura, Akira
Vacuole-mediated selective regulation of TORC1-Sch9 signaling following oxidative stress
title Vacuole-mediated selective regulation of TORC1-Sch9 signaling following oxidative stress
title_full Vacuole-mediated selective regulation of TORC1-Sch9 signaling following oxidative stress
title_fullStr Vacuole-mediated selective regulation of TORC1-Sch9 signaling following oxidative stress
title_full_unstemmed Vacuole-mediated selective regulation of TORC1-Sch9 signaling following oxidative stress
title_short Vacuole-mediated selective regulation of TORC1-Sch9 signaling following oxidative stress
title_sort vacuole-mediated selective regulation of torc1-sch9 signaling following oxidative stress
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6014174/
https://www.ncbi.nlm.nih.gov/pubmed/29237820
http://dx.doi.org/10.1091/mbc.E17-09-0553
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