The Molecular Logic of Gtr1/2 and Pib2 Dependent TORC1 Regulation in Budding Yeast

Cecil, J. H.; Padilla, C. M.; Lipinski, A. A.; Langlais, P.; Luo, X.; Capaldi, A. P.

doi:10.1101/2023.12.06.570342

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bioRxiv · 10.1101/2023.12.06.570342

The Molecular Logic of Gtr1/2 and Pib2 Dependent TORC1 Regulation in Budding Yeast

Cecil, J. H.·Padilla, C. M.·Lipinski, A. A.·Langlais, P.·Luo, X.·Capaldi, A. P.

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Abstract

The Target of Rapamycin kinase Complex I (TORC1) regulates cell growth and metabolism in eukaryotes. Previous studies have shown that, in Saccharomyces cerevisiae, nitrogen and amino acid signals activate TORC1 via the highly conserved small GTPases, Gtr1/2, and the phosphatidylinositol 3-phosphate binding protein, Pib2. However, it was unclear if/how Gtr1/2 and Pib2 cooperate to control TORC1. Here we report that this dual regulator system pushes TORC1 into at least three distinct signaling states: (i) a Gtr1/2 on, Pib2 on, rapid growth state in nutrient replete conditions; (ii) a Gtr1/2 inhibited, Pib2 on, adaptive/slow growth state in poor-quality growth medium; and (iii) a Gtr1/2 off, Pib2 off, quiescent state in starvation conditions. We suggest that other signaling pathways work in a similar way, to drive a multi-level response via a single kinase, but the behavior has been overlooked since most studies follow signaling to a single reporter protein.

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Cecil, J. H., Padilla, C. M., Lipinski, A. A., Langlais, P., Luo, X., Capaldi, A. P.. 2023-12-07. The Molecular Logic of Gtr1/2 and Pib2 Dependent TORC1 Regulation in Budding Yeast. https://doi.org/10.1101/2023.12.06.570342

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