Abstract
Quiescence and gametogenesis represent two distinct survival strategies in response to nutrient starvation in budding yeast. Precisely how environmental signals are sensed by yeast cells to trigger quiescence and gametogenesis is not fully understood. A conserved signalling module consisting of Greatwall kinase, Endosulfine and Protein Phosphatase PP2ACdc55 proteins regulates entry into mitosis in Xenopus egg extracts and meiotic maturation in flies. We report here that an analogous signalling module consisting of the serine-threonine kinase Rim15, the Endosulfines Igo1 and Igo2 and the Protein Phosphatase PP2ACdc55, regulates entry into both quiescence and gametogenesis in budding yeast. PP2ACdc55 inhibits entry into gametogenesis and quiescence. Rim15 promotes entry into gametogenesis and quiescence by converting Igo1 into an inhibitor of PP2ACdc55 by phosphorylating at a conserved serine residue. Moreover, we show that the Rim15-Endosulfine-PP2ACdc55 pathway regulates entry into quiescence and gametogenesis by distinct mechanisms. In addition, we show that Igo1 and Igo2 are required for pre-meiotic autophagy but the lack of pre-meiotic autophagy is insufficient to explain the sporulation defect of igo1Δ igo2Δ cells. We propose that the Rim15-Endosulfine-PP2ACdc55 signalling module triggers entry into quiescence and gametogenesis by regulating dephosphorylation of distinct substrates.
Highlights
The ability of cells to sense deleterious changes in environment and mount an appropriate physiological and metabolic response is essential for cellular survival
The module consists of three molecular components namely a serine-threonine kinase Rim15, a phosphatase PP2ACdc55 and a conserved protein called as endosulfine
Rim15 becomes active and phosphorylates endosulfine. This converts endosulfine to an inhibitor of PP2ACdc55 and thereby leading to entry into quiescence and gametogenesis
Summary
The ability of cells to sense deleterious changes in environment and mount an appropriate physiological and metabolic response is essential for cellular survival. Yeast cells enter either gametogenesis or quiescence. Diploid yeast cells undergo gametogenesis when subjected to nitrogen starvation in the absence of glucose and in the presence of a non-fermentable carbon source. They undergo one round of DNA replication followed by two rounds of nuclear divisions to form 4 haploid spores which can stay dormant for long periods of time. Haploid and diploid cells enter quiescence when subjected to nutrient starvation or when treated with a drug called rapamycin, an inhibitor of the TOR (Target of Rapamycin) signalling pathway. Ablation of G0-entry/exit control mechanisms is frequently linked to either reduced life span (especially in unicellular organisms) or cellular transformation (in multi-cellular organisms) [4,5]
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