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

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Martín, R 
Portantier, M 
Chica, N 
Nyquist-Andersen, M 

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.

sexual differentiation, nitrogen starvation, TORC1, TORC2, Gad8, PP2A, B55, S. pombe
Journal Title
Current Biology
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Elsevier (Cell Press)
Biotechnology and Biological Sciences Research Council (BB/M021483/1)
BBSRC (BB/N07697/1)
We thank Dominique Helmlinger and Sergio Moreno for sharing unpublished results and strains, and for stimulating discussion. We thank Janni Petersen, Ronit Weisman, Kazuhiro Shiozaki, Mitsuhiro Yanagida, and Hisao Masukata for strains, constructs, and antibodies. We thank Toni Hurtado and Beata Grallert for critical reading of the manuscript. This work was supported by NFR FRIMEDBIO grant 214049. M.P. is the recipient of a Kreftforeningen postdoctoral fellowship (grant 5843744). N.C. has received funding from the European Union Seventh Framework Programme (FP7-PEOPLE-2013-COFUND) under grant agreement 609020 - Scientia Fellows. J.M. was supported by BBSRC research grants BB/N007697/1 and BB/M021483/1.