@article{1dadb00e87bb4b93b0cf804160c3aeac,
title = "Ypk1 and Ypk2 kinases maintain Rho1 at the plasma membrane by flippase-dependent lipid remodeling after membrane stresses",
abstract = "The plasma membrane (PM) is frequently challenged by mechanical stresses. In budding yeast, TORC2-Ypk1/Ypk2 kinase cascade plays a crucial role in PM stress responses by reorganizing the actin cytoskeleton via Rho1 GTPase. However, the molecular mechanism by which TORC2-Ypk1/Ypk2 regulates Rho1 is not well defined. Here, we found that Ypk1/Ypk2 maintain PM localization of Rho1 under PM stress via spatial reorganization of the lipids including phosphatidylserine. Genetic evidence suggests that this process is mediated by the Lem3-containing lipid flippase.We propose that lipid remodeling mediated by the TORC2-Ypk1/Ypk2-Lem3 axis is a backup mechanism for PM anchoring of Rho1 after PM stressinduced acute degradation of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], which is responsible for Rho1 localization under normal conditions. Since all the signaling molecules studied here are conserved in higher eukaryotes, our findings might represent a general mechanism to cope with PM stress.",
keywords = "Actin cytoskeleton, Akt, Flippase, Membrane stress, Phosphatidylserine, Rho",
author = "Riko Hatakeyama and Keiko Kono and Satoshi Yoshida",
note = "Funding Information: We thank Tomohiko Taguchi (Univ. Tokyo, Tokyo, Japan) and Shoken Lee (Univ. Tokyo, Tokyo, Japan) for providing plasmids and for insightful discussions.We thank Scott Emr (Cornell, Ithaca, USA), Yoshikazu Ohya (Univ. Tokyo, Kashiwa, Japan), Daniel Lew (Duke, Durham, USA), Jeremy Thorner (UC Berkeley, Berkeley, USA) and David Pellman (Harvard, Boston, USA) for providing strains and plasmids. We thank members of the Yoshida Lab and Nan Pang for technical support, and helpful discussions. This work was supported by a Japan Society for the Promotion of Science (JSPS) KAKENHI Grant [grant number JP16H04781], by the Takeda Science Foundation, and by a joint research program of the Institute for Molecular and Cellular Regulation, Gunma University, Japan. Publisher Copyright: {\textcopyright} 2017. Published by The Company of Biologists Ltd.",
year = "2017",
doi = "10.1242/jcs.198382",
language = "English",
volume = "130",
pages = "1169--1178",
journal = "The Quarterly journal of microscopical science",
issn = "0021-9533",
publisher = "Company of Biologists Ltd",
number = "6",
}