Ypk1 and Ypk2 kinases maintain Rho1 at the plasma membrane by flippase-dependent lipid remodeling after membrane stresses.
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 stress-induced 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.
Department of Biology and Rosenstiel Basic Biomedical Research Center, Brandeis University, 415 South Street, Waltham, MA 02454, USA riko.hatakeyama@unifr.ch satoshi@gunma-u.ac.jp.|Department of Biology, University of Fribourg, Chemin du Musée 10, Fribourg CH-1700, Switzerland.
Riko
0000-0002-3065-6639
R
Hatakeyama
Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Keiko
K
Kono
Department of Biology and Rosenstiel Basic Biomedical Research Center, Brandeis University, 415 South Street, Waltham, MA 02454, USA riko.hatakeyama@unifr.ch satoshi@gunma-u.ac.jp.|Gunma Initiative for Advanced Research (GIAR), Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma 371-8512, Japan.|Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma 371-8512, Japan.
Satoshi
S
Yoshida
D001483:Base Sequence; D002462:Cell Membrane / Q000378:metabolism*; D008055:Lipids / Q000737:chemistry*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D049294:Phospholipid Transfer Proteins / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D013312:Stress, Physiological; D013379:Substrate Specificity; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D008055:Lipids; D019269:Phosphatidylinositol 4,5-Diphosphate; D010718:Phosphatidylserines; D049294:Phospholipid Transfer Proteins; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C060388:YPK2 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C000621797:YPK1 protein, S cerevisiae; C051302:RHO1 protein, S cerevisiae; D020741:rho GTP-Binding Proteins
Actin cytoskeleton; Akt; Flippase; Membrane stress; Phosphatidylserine; Rho