A PP2A-B55-Mediated Crosstalk between TORC1 and TORC2 Regulates the Differentiation Response in Fission Yeast
| Autor: | Martîn, Ruth Martîn, Portantier, Marina, Chica-Balaguera, Nathalia, Nyquist-Andersen, Mari, Mata, J, Lopez-Aviles, Sandra |
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| Přispěvatelé: | Mata, Juan [0000-0002-5514-3653], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
S. pombe
Agricultural and Biological Sciences(all) Biochemistry Genetics and Molecular Biology(all) Nitrogen Gad8 sexual differentiation Mechanistic Target of Rapamycin Complex 2 Mechanistic Target of Rapamycin Complex 1 Article TORC2 TORC1 PP2A Multiprotein Complexes Schizosaccharomyces nitrogen starvation Schizosaccharomyces pombe Proteins Phosphorylation B55 Signal Transduction |
| Zdroj: | Current Biology |
| ISSN: | 0960-9822 |
| Popis: | Summary 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. Graphical Abstract Highlights • PP2A-B55Pab1 regulates the differentiation response of fission yeast cells • PP2A-B55Pab1 enables a crosstalk between TORC1 and TORC2 • TORC1 favors PP2A-B55Pab1 activity to prevent the hyperphosphorylation of Gad8 • TORC1 inactivation leads to PP2A-B55Pab1 inhibition, activation of Gad8, and differentiation TORC1 and TORC2 play opposite roles in the differentiation response of fission yeast. Here, Martin et al. show that PP2A-B55Pab1 coordinates the activities of these two modules in response to nitrogen availability, thus connecting nutritional status to cell-fate decisions. |
| Databáze: | OpenAIRE |
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