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Pib2 is a cysteine sensor involved in TORC1 activation in Saccharomyces cerevisiae

Qingzhong Zeng1, Yasuhiro Araki2, Takeshi Noda3

  • 1Graduate School of Frontier Biosciences, Osaka University, Osaka 565-0871, Japan.

Cell Reports
|December 21, 2023
PubMed

Insights

Target of rapamycin complex 1 (TORC1) regulates cell growth by sensing amino acids. This study reveals cysteine directly activates TORC1 via the Pib2 pathway, identifying Pib2 as a cysteine sensor.

Area of Science:

  • Cellular biology
  • Molecular mechanisms of nutrient sensing
  • Yeast as a model organism

Background:

  • Target of rapamycin complex 1 (TORC1) is crucial for cell growth, integrating nutrient availability signals.
  • TORC1 activation in Saccharomyces cerevisiae involves the Gtr and Pib2 pathways.
  • Amino acid availability dictates TORC1 pathway utilization.

Purpose of the Study:

  • To elucidate the specific roles of the Gtr and Pib2 pathways in TORC1 activation by individual amino acids.
  • To investigate the mechanism by which cysteine influences TORC1 signaling.
  • To identify the direct interaction between cysteine and its sensor protein.

Main Methods:

  • Phosphorylation analysis of TORC1 substrate Ser3 to indicate pathway activity.
  • Assessing TORC1 activity using the substrate Sch9.
  • In vivo and in vitro interaction studies between TORC1, Pib2, and cysteine.
  • Site-directed mutagenesis to identify critical residues in Pib2.

Main Results:

  • Different amino acids display distinct dependencies on the Gtr and Pib2 pathways for TORC1 activation.
  • Cysteine exhibits a strong dependence on the Pib2 pathway.
  • Cysteine directly binds to Pib2 at residues W632 and F635 within the T(ail) motif, enhancing TORC1-Pib2 interaction.
  • Pib2 acts as a direct sensor for cysteine.

Conclusions:

  • Pib2 is identified as a specific cysteine sensor for TORC1 regulation.
  • Cysteine directly activates TORC1 through Pib2-mediated signaling.
  • This study reveals a novel mechanism of amino acid sensing in nutrient-regulated growth.
Keywords:
CP: Molecular biologyCysteinePib2TORC1mTORC1

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