The TOR Complex 1 Is a Direct Target of Rho1 GTPase

Yan, Gonghong; Lai, Yisheng; Jiang, Yu

doi:10.1016/j.molcel.2012.01.028

Cited by 77 publications

(125 citation statements)

References 45 publications

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“…This suggests that the change in Rom2-dependent phosphorylation of Elo2 does not involve the downstream cell wall integrity pathway signaling kinases, such as Slt2. Instead, the signal from RhoGTP may be transduced through another one of its targets, the TORC1 complex (49). Control of TORC1 could relay the information on plasma membrane SL levels to Mck1, a GSK3-like kinase in yeast that mediates Elo2 phosphorylation in the ER (45).…”

Section: Discussionmentioning

confidence: 99%

Rom2-dependent Phosphorylation of Elo2 Controls the Abundance of Very Long-chain Fatty Acids

Olson

Fröhlich

Christiano

et al. 2015

Journal of Biological Chemistry

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Background: Sphingolipids are synthesized from very long-chain fatty acids and sphingoid bases. Results: Rom2 controls Elo2 phosphorylation to regulate very long-chain fatty acid synthesis. Conclusion: Distinct signaling pathways emanating from the plasma membrane regulate the different branches of sphingolipid synthesis. Significance: Signaling from the plasma membrane regulates a key step in sphingolipid synthesis, required for lipid homeostasis of the plasma membrane.

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Section: Discussionmentioning

confidence: 99%

Rom2-dependent Phosphorylation of Elo2 Controls the Abundance of Very Long-chain Fatty Acids

Olson

Fröhlich

Christiano

et al. 2015

Journal of Biological Chemistry

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“…We find that these proteins, known to bind TORC1 at the vacuolar membrane, and in the case of Rho1 to alter its interaction with Tap42-PP2A (Sancak et al 2008(Sancak et al , 2010Binda et al 2009;Yan et al 2012), primarily influence the TORC1 pathway in nitrogen/ amino acid starvation conditions. We also demonstrate that the AMP-activated protein kinase (AMPK/Snf1) inhibits signaling through the TORC1 pathway in glucose starvation conditions, while the MAPK Hog1/p38 inhibits signaling through the TORC1 pathway in osmotic stress.…”

mentioning

confidence: 85%

“…The metabolic pathways are, to a large degree, regulated by the Tap42/PP2A protein phosphatases (Beck and Hall 1999;Jacinto et al 2001;Duvel et al 2003;Santhanam et al 2004;Huber et al 2009). The activity of the PP2A complex, which includes the regulator Tap42, depends on both a physical interaction with and phosphorylation by TORC1 (Jiang and Broach 1999;Yan et al 2006Yan et al , 2012. Kinases are shown in blue, transcription factors in red, and phosphatases in green.…”

Section: Gene Expression Microarray Experimentsmentioning

confidence: 99%

“…Gln3 had a (moderate) bandshift, similar to that found for several the other targets, but was chosen since it has been used in other studies examining PP2A signaling (Cox et al 2004;Tate et al 2009;Yan et al 2012). To ensure consistent results all subsequent bandshift experiments (including for Sch9, Dot6, Tod6, and the Npr1 target Par32) were run at 80 V for 3 hr on a 10% acrylamide gel (Sch9), a 7.5% acrylamide gel (Dot6, Tod6, and Par32), or a 5% acrylamide gel (Gln3, Npr1, and Nnk1).…”

Section: Bandshift Experimentsmentioning

confidence: 99%

“…To probe the mechanisms underlying the conditiondependent output of the TORC1 pathway we also examined the influence that the known nitrogen/amino acid response regulators-the Rag proteins Gtr1/Gtr2 (Sancak et al 2008;Binda et al 2009), the small GTPase Rho1 (Yan et al 2012), and the SEA-associated proteins Npr2/Npr3 (Neklesa and Davis 2009;Panchaud et al 2013)-have on TORC1 pathway signaling in different conditions. We find that these proteins, known to bind TORC1 at the vacuolar membrane, and in the case of Rho1 to alter its interaction with Tap42-PP2A (Sancak et al 2008(Sancak et al , 2010Binda et al 2009;Yan et al 2012), primarily influence the TORC1 pathway in nitrogen/ amino acid starvation conditions.…”

mentioning

confidence: 99%

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State Transitions in the TORC1 Signaling Pathway and Information Processing in Saccharomyces cerevisiae

2014

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TOR kinase complex I (TORC1) is a key regulator of cell growth and metabolism in all eukaryotes. Previous studies in yeast have shown that three GTPases-Gtr1, Gtr2, and Rho1-bind to TORC1 in nitrogen and amino acid starvation conditions to block phosphorylation of the S6 kinase Sch9 and activate protein phosphatase 2A (PP2A). This leads to downregulation of 450 Sch9-dependent protein and ribosome synthesis genes and upregulation of 100 PP2A-dependent nitrogen assimilation and amino acid synthesis genes. Here, using bandshift assays and microarray measurements, we show that the TORC1 pathway also populates three other stress/starvation states. First, in glucose starvation conditions, the AMP-activated protein kinase (AMPK/Snf1) and at least one other factor push the TORC1 pathway into an off state, in which Sch9-branch signaling and PP2A-branch signaling are both inhibited. Remarkably, the TORC1 pathway remains in the glucose starvation (PP2A inhibited) state even when cells are simultaneously starved for nitrogen and glucose. Second, in osmotic stress, the MAPK Hog1/p38 drives the TORC1 pathway into a different state, in which Sch9 signaling and PP2A-branch signaling are inhibited, but PP2A-branch signaling can still be activated by nitrogen starvation. Third, in oxidative stress and heat stress, TORC1-Sch9 signaling is blocked while weak PP2A-branch signaling occurs. Together, our data show that the TORC1 pathway acts as an information-processing hub, activating different genes in different conditions to ensure that available energy is allocated to drive growth, amino acid synthesis, or a stress response, depending on the needs of the cell.

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Hyperactive TORC1 sensitizes yeast cells to endoplasmic reticulum stress by compromising cell wall integrity

2019

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Edited by Michael IbbaAccumulation of misfolded proteins in the endoplasmic reticulum (ER) activates the unfolded protein response (UPR). Here, we investigated how the target of rapamycin complex 1 (TORC1) signaling cascade acts in parallel with the UPR to regulate ER stress sensitivity. Using Saccharomyces cerevisiae, we found that TORC1 signaling is attenuated during ER stress and constitutive activation of TORC1 increases sensitivity to ER stressors independently of the UPR. Transcriptome analysis revealed that TORC1 hyperactivation results in cell wall remodelling. Conversely, hyperactive TORC1 sensitizes cells to cell wall stressors, including the antifungal caspofungin. Elucidating the crosstalk between the UPR, cell wall integrity, and TORC1 signaling may uncover new paradigms through which the response to protein misfolding is regulated.

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The TOR Complex 1 Is a Direct Target of Rho1 GTPase

Cited by 77 publications

References 45 publications

Rom2-dependent Phosphorylation of Elo2 Controls the Abundance of Very Long-chain Fatty Acids

Rom2-dependent Phosphorylation of Elo2 Controls the Abundance of Very Long-chain Fatty Acids

State Transitions in the TORC1 Signaling Pathway and Information Processing in Saccharomyces cerevisiae

Hyperactive TORC1 sensitizes yeast cells to endoplasmic reticulum stress by compromising cell wall integrity

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