Wilms Tobias, Swinnen Erwin, Eskes Elja, Dolz-Edo Laura, Uwineza Alice, Van Essche Ruben, Rosseels Joëlle, Zabrocki Piotr, Cameroni Elisabetta, Franssens Vanessa, De Virgilio Claudio, Smits Gertien J, Winderickx Joris
Department of Biology, Functional Biology, KU Leuven, Heverlee, Belgium.
Department of Molecular Biology and Microbial Food Safety, Swammerdam Institute for Life Sciences, University of Amsterdam, GE Amsterdam, The Netherlands.
PLoS Genet. 2017 Jun 12;13(6):e1006835. doi: 10.1371/journal.pgen.1006835. eCollection 2017 Jun.
The conserved protein kinase Sch9 is a central player in the nutrient-induced signaling network in yeast, although only few of its direct substrates are known. We now provide evidence that Sch9 controls the vacuolar proton pump (V-ATPase) to maintain cellular pH homeostasis and ageing. A synthetic sick phenotype arises when deletion of SCH9 is combined with a dysfunctional V-ATPase, and the lack of Sch9 has a significant impact on cytosolic pH (pHc) homeostasis. Sch9 physically interacts with, and influences glucose-dependent assembly/disassembly of the V-ATPase, thereby integrating input from TORC1. Moreover, we show that the role of Sch9 in regulating ageing is tightly connected with V-ATPase activity and vacuolar acidity. As both Sch9 and the V-ATPase are highly conserved in higher eukaryotes, it will be interesting to further clarify their cooperative action on the cellular processes that influence growth and ageing.
保守的蛋白激酶Sch9是酵母中营养诱导信号网络的核心参与者，尽管已知其直接底物很少。我们现在提供证据表明，Sch9控制液泡质子泵（V-ATPase）以维持细胞pH稳态和衰老。当SCH9缺失与功能失调的V-ATPase结合时会出现合成病态表型，并且Sch9的缺失对细胞质pH（pHc）稳态有重大影响。Sch9与V-ATPase发生物理相互作用，并影响其依赖葡萄糖的组装/拆卸，从而整合来自TORC1的输入。此外，我们表明Sch9在调节衰老中的作用与V-ATPase活性和液泡酸度紧密相关。由于Sch9和V-ATPase在高等真核生物中都高度保守，进一步阐明它们在影响生长和衰老的细胞过程中的协同作用将很有趣。
