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.
Bibliographical note© 2017. Published by The Company of Biologists Ltd.
- Base Sequence
- Cell Membrane/metabolism
- Phosphatidylinositol 4,5-Diphosphate/metabolism
- Phospholipid Transfer Proteins/metabolism
- Protein Kinases/metabolism
- Protein Transport
- Protein-Serine-Threonine Kinases/metabolism
- Saccharomyces cerevisiae/metabolism
- Saccharomyces cerevisiae Proteins/metabolism
- Stress, Physiological
- Substrate Specificity
- rho GTP-Binding Proteins/metabolism