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A PP2A-B55-Mediated Crosstalk between TORC1 and TORC2 Regulates the Differentiation Response in Fission Yeast

Ruth Martín1, Marina Portantier1, Nathalia Chica1

  • 1The Biotechnology Centre of Oslo, University of Oslo, Gaustadalléen 21, Oslo 0349, Norway.

Current Biology : CB
|January 3, 2017
PubMed

Insights

The phosphatase PP2A-B55Pab1 controls cell fate by linking TORC1 and TORC2 signaling. Its inactivation promotes sexual differentiation by activating TORC2-AKT signaling (Gad8).

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Extracellular cues regulate cell fate via transcriptional programs.
  • TORC1 and TORC2 complexes integrate nutritional signals, but their interplay is unclear.
  • Phosphatase activity's role in TORC1/TORC2 interplay during cell differentiation is understudied.

Purpose of the Study:

  • Investigate the role of phosphatase activity in TORC1/TORC2 interplay.
  • Elucidate the mechanism controlling the switch from proliferation to sexual differentiation in fission yeast.
  • Determine how PP2A-B55Pab1 influences TORC1 and TORC2 signaling.

Main Methods:

  • Fission yeast as a model organism.
  • Genetic manipulation (gene deletion and overexpression).
  • Transcriptional profiling.
  • Analysis of signaling pathways (TORC1, TORC2-AKT/Gad8).

Main Results:

  • Loss of PP2A-B55Pab1 enhances differentiation gene expression and causes premature conjugation.
  • PP2A-B55Pab1 inactivation mimics TORC1 inactivation and overcomes TORC1-mediated repression of differentiation.
  • This effect is mediated by increased TORC2-AKT (Gad8) signaling, as PP2A-B55Pab1 dephosphorylates and represses Gad8 activity under nutrient-rich conditions.

Conclusions:

  • PP2A-B55Pab1 acts as a crucial crosstalk mediator between TORC1 and TORC2.
  • Nutrient availability, sensed by TORC1, regulates PP2A-B55Pab1 activity via the Greatwall-Endosulfin pathway.
  • Inactivation of PP2A-B55Pab1 upon starvation activates TORC2-Gad8 signaling, committing cells to differentiation.
Keywords:
B55Gad8PP2AS. pombeTORC1TORC2nitrogen starvationsexual differentiation

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