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, , TORC1 senses nitrogen and various stressors and modulates proteosynthesis, nitrogen uptake and metabolism, stress responses, and autopha...

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Bibliographic Details
Published in:Molecular biology of the cell 2018-02, Vol.29 (4), p.510-522
Main Authors: Takeda, Eigo, Jin, Natsuko, Itakura, Eisuke, Kira, Shintaro, Kamada, Yoshiaki, Weisman, Lois S, Noda, Takeshi, Matsuura, Akira
Format: Article
Language:English
Subjects:
Gene Expression Regulation, Fungal
Gene Regulatory Networks
Microscopy, Fluorescence
Oxidative Stress - genetics
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - metabolism
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - growth & development
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - metabolism
Signal Transduction
Transcription Factors - genetics
Transcription Factors - metabolism
Vacuoles - metabolism
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Summary: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, , 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.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.e17-09-0553