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Review
. 2018 Feb;64(1):43-51.
doi: 10.1007/s00294-017-0721-8. Epub 2017 Jun 22.

Express yourself: how PP2A-B55Pab1 helps TORC1 talk to TORC2

Ruth Martín  1 , Sandra Lopez-Aviles  2
Affiliations
Review

Express yourself: how PP2A-B55Pab1 helps TORC1 talk to TORC2

Ruth Martín et al. Curr Genet. 2018 Feb.

Abstract

The control of cell fate, growth and proliferation in response to nitrogen availability is a tightly controlled process, with the two TOR complexes (TORC1 and TORC2) and their effectors playing a central role. PP2A-B55Pab1 has recently been shown to be a key element in this response in fission yeast, where it regulates cell cycle progression and sexual differentiation. Importantly, a recent study from our group has shown that PP2A-B55Pab1 acts as a mediator between the activities of the two TOR signaling modules, enabling a crosstalk that is required to engage in the differentiation program. In this review, we recapitulate the studies that have led to our current understanding of the interplay between TOR complexes. Moreover, we discuss several aspects of the response to nitrogen availability that still require further attention, and which will be important in the future to fully realize the implications of phosphatase activity in the context of TOR signaling.

Keywords: Differentiation; Gad8; Nitrogen signaling; PP2A-B55; TORC1; TORC2.

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Figures

Fig. 1
Fig. 1
Current understanding of PP2A-B55Pab1 regulation and functions and future directions. Arrows depicted in black represent established events, whereas arrows in grey indicate potential regulations that would require further investigation (see main text for details). (1) PP2A-B55Pab1 lies downstream of TORC1 in the response to nitrogen availability, preventing the differentiation response. During growth on nitrogen-rich medium, TORC1 activity leads to the inhibition of Ppk18. In this condition, the Ppk18 substrate Igo1 is not phosphorylated and cannot act as an inhibitor of PP2A-B55Pab1. Active PP2A-B55Pab1 regulates several events downstream: (2) it prevents the G2/M transition, extending the length of the G2 phase and delaying mitotic entry; (3) it reverts the phosphorylation of Gad8 by TORC2 on Ser546, preventing sexual differentiation. In response to nitrogen starvation, low TORC1 activity prompts the reactivation of Ppk18 and inhibition of PP2A-B55Pab1. In this situation PP2A-B55Pab1 can neither exert its repressive role on mitotic entry, nor prevent Gad8 Ser546 hyperphosphorylation. Altogether this leads to cell shortening, arrest in G1 phase and activation of the sexual differentiation program. (4) Other events in the regulation of Gad8 function: Gad8 shuttles between nucleus and cytoplasm, but the implications of its localization in its function and regulation have not been ascertained. Little is known about the dephosphorylation of the turn motif and the activation loop of Gad8 by protein phosphatases (depicted as PPase X and Y). (5) Other targets of PP2A-B55Pab1 are likely contributors to the transcriptional events brought about by the inactivation of PP2A-B55Pab1
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