Nutritional Control of Cell Size by the Greatwall-Endosulfine-PP2A·B55 Pathway

• Published in: Current biology 2016-02, Vol.26 (3), p.319-330
• Main Authors: Chica, Nathalia, Rozalén, Ana Elisa, Pérez-Hidalgo, Livia, Rubio, Angela, Novak, Bela, Moreno, Sergio
• Format: Article
• Language: English
• Subjects: B55; Cell Cycle; Cell Cycle Proteins - metabolism; cell size; endosulfine; greatwall; Igo1; Mechanistic Target of Rapamycin Complex 1; Multiprotein Complexes - metabolism; Nutritional Physiological Phenomena; Peptides - metabolism; PP2A; Ppk18; S. pombe; Schizosaccharomyces - physiology; Schizosaccharomyces pombe Proteins - metabolism; Signal Transduction; TOR; TOR Serine-Threonine Kinases - metabolism
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2015.12.035

Proliferating cells adjust their cell size depending on the nutritional environment. Cells are large in rich media and small in poor media. This physiological response has been demonstrated in both unicellular and multicellular organisms. Here we show that the greatwall-endosulfine (Ppk18-Igo1 in fission yeast) pathway couples the nutritional environment to the cell-cycle machinery by regulating the activity of PP2A·B55. In the presence of nutrients, greatwall (Ppk18) protein kinase is inhibited by TORC1 and PP2A·B55 is active. High levels of PP2A·B55 prevent the activation of mitotic Cdk1·Cyclin B, and cells increase in size in G2 before they undergo mitosis. When nutrients are limiting, TORC1 activity falls off, and the activation of greatwall (Ppk18) leads to the phosphorylation of endosulfine (Igo1) and inhibition of PP2A·B55, which in turn allows full activation of Cdk1·CyclinB and entry into mitosis with a smaller cell size. Given the conservation of this pathway, it is reasonable to assume that this mechanism operates in higher eukaryotes, as well. [Display omitted] •The greatwall-endosulfine-PP2A·B55 pathway links TORC1 to the mitotic control•High levels of PP2A·B55 activity delay entry into mitosis•In rich media, TORC1 inhibits greatwall, PP2A·B55 is active, and the cells are large•In poor media, activation of greatwall inhibits PP2A·B55 and the cells become small Cells are large in rich media and small in poor media. Here, Chica et al. show that the greatwall-endosulfine pathway couples the nutritional environment to the cell-cycle machinery by regulating the activity of PP2A·B55. This pathway links cell growth (TORC1) with cell division (Cdk1) and controls cell size homeostasis in fission yeast