title: A PP2A-B55-Mediated Crosstalk between TORC1 and TORC2 Regulates the Differentiation Response in Fission Yeast.
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-B55Pab1enhances 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-B55Pab1dephosphorylates Gad8 Ser546, repressing its activity. Conversely, TORC1 inactivation upon starvation leads to the inactivation of PP2A-B55Pab1through the Greatwall-Endosulfin pathway. This results in the activation of Gad8 and the commitment to differentiation. Thus, PP2A-B55Pab1enables a crosstalk between the two TOR complexes that controls cell-fate decisions in response to nutrient availability.
authors.affiliation: The Biotechnology Centre of Oslo, University of Oslo, Gaustadalléen 21, Oslo 0349, Norway.
authors.forename: Ruth
authors.initials: R
authors.lastname: Martín
authors.affiliation: The Biotechnology Centre of Oslo, University of Oslo, Gaustadalléen 21, Oslo 0349, Norway.
authors.forename: Marina
authors.initials: M
authors.lastname: Portantier
authors.affiliation: The Biotechnology Centre of Oslo, University of Oslo, Gaustadalléen 21, Oslo 0349, Norway.
authors.forename: Nathalia
authors.initials: N
authors.lastname: Chica
authors.affiliation: The Biotechnology Centre of Oslo, University of Oslo, Gaustadalléen 21, Oslo 0349, Norway.
authors.forename: Mari
authors.initials: M
authors.lastname: Nyquist-Andersen
authors.affiliation: Department of Biochemistry, University of Cambridge, Building O, Downing Site, Cambridge CB2 1QW, UK.
authors.forename: Juan
authors.initials: J
authors.lastname: Mata
authors.affiliation: The Biotechnology Centre of Oslo, University of Oslo, Gaustadalléen 21, Oslo 0349, Norway. Electronic address: sandra.lopez-aviles@biotek.uio.no.
authors.forename: Sandra
authors.initials: S
authors.lastname: Lopez-Aviles
mesh_terms: D000076222:Mechanistic Target of Rapamycin Complex 1 / Q000235:genetics / Q000378:metabolism*; D000076225:Mechanistic Target of Rapamycin Complex 2 / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D009584:Nitrogen / Q000378:metabolism; D010766:Phosphorylation; D012568:Schizosaccharomyces / Q000166:cytology / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D046912:Multiprotein Complexes; D029702:Schizosaccharomyces pombe Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D009584:Nitrogen
keywords: B55; Gad8; PP2A; S. pombe; TORC1; TORC2; nitrogen starvation; sexual differentiation