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Curr Biol. 2017 Jan 23;27(2):175-188. doi: 10.1016/j.cub.2016.11.037. Epub 2016 Dec 29.

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

Author information

1
The Biotechnology Centre of Oslo, University of Oslo, Gaustadalléen 21, Oslo 0349, Norway.
2
Department of Biochemistry, University of Cambridge, Building O, Downing Site, Cambridge CB2 1QW, UK.
3
The Biotechnology Centre of Oslo, University of Oslo, Gaustadalléen 21, Oslo 0349, Norway. Electronic address: sandra.lopez-aviles@biotek.uio.no.

Abstract

Extracellular cues regulate cell fate, and this is mainly achieved through the engagement of specific transcriptional programs. The TORC1 and TORC2 complexes mediate the integration of nutritional cues to cellular behavior, but their interplay is poorly understood. Here, we use fission yeast to investigate how phosphatase activity participates in this interplay during the switch from proliferation to sexual differentiation. We find that loss of PP2A-B55Pab1 enhances the expression of differentiation-specific genes and leads to premature conjugation. pab1 deletion brings about a transcriptional profile similar to TORC1 inactivation, and deletion of pab1 overcomes the repression of differentiation genes in cells overexpressing TORC1. Importantly, we show that this effect is mediated by an increased TORC2-AKT (Gad8) signaling. Under nutrient-rich conditions, PP2A-B55Pab1 dephosphorylates Gad8 Ser546, repressing its activity. Conversely, TORC1 inactivation upon starvation leads to the inactivation of PP2A-B55Pab1 through the Greatwall-Endosulfin pathway. This results in the activation of Gad8 and the commitment to differentiation. Thus, PP2A-B55Pab1 enables a crosstalk between the two TOR complexes that controls cell-fate decisions in response to nutrient availability.

KEYWORDS:

B55; Gad8; PP2A; S. pombe; TORC1; TORC2; nitrogen starvation; sexual differentiation

PMID:
28041796
PMCID:
PMC5266790
DOI:
10.1016/j.cub.2016.11.037
[Indexed for MEDLINE]
Free PMC Article

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