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The molecular logic of Gtr1/2- and Pib2-dependent TORC1 regulation in budding yeast

Jacob H Cecil1, Cristina M Padilla1, Austin A Lipinski2

  • 1Department of Molecular and Cellular Biology, University of Arizona, Tucson, United States.

Elife
|July 7, 2025
PubMed

Insights

The Target of Rapamycin kinase Complex 1 (TORC1) signaling is controlled by Gtr1/2 and Pib2, enabling distinct growth states. This dual regulation allows yeast to adapt to nutrient availability, from rapid growth to quiescence.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The Target of Rapamycin kinase Complex 1 (TORC1) is a crucial regulator of cell growth and metabolism in eukaryotes.
  • In yeast (Saccharomyces cerevisiae), TORC1 activation by nutrients involves Gtr1/2 GTPases and Pib2 protein, but their cooperative mechanism was unclear.

Purpose of the Study:

  • To elucidate the cooperative roles of Gtr1/2 and Pib2 in regulating TORC1 signaling.
  • To define the distinct cellular states controlled by this dual regulatory system.

Main Methods:

  • Investigated the interplay between Gtr1/2 and Pib2 in yeast.
  • Analyzed TORC1 signaling states under varying nutrient conditions.

Main Results:

  • Identified three distinct TORC1 signaling states governed by Gtr1/2 and Pib2 activity.
  • State 1 (Nutrient-rich): Gtr1/2 ON, Pib2 ON, leading to rapid growth.
  • State 2 (Poor-medium): Gtr1/2 inhibited, Pib2 ON, resulting in adaptive/slow growth.
  • State 3 (Starvation): Gtr1/2 OFF, Pib2 OFF, inducing a quiescent state.

Conclusions:

  • The Gtr1/2 and Pib2 system provides a multilevel control mechanism for TORC1 signaling.
  • This dual regulation enables yeast to precisely adapt growth responses to environmental nutrient availability.
  • Suggests similar multilevel regulatory strategies may exist for other signaling pathways, previously overlooked due to single reporter monitoring.
Keywords:
Gtr1/2Pib2S. cerevisiaeTORC1cell biologynutrientprotein kinase

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