Ypk1 and Ypk2 kinases maintain Rho1 at the plasma membrane by flippase-dependent lipid remodeling after membrane stresses

Riko Hatakeyama, Keiko Kono, Satoshi Yoshida

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1169-1178
Number of pages10
JournalJournal of Cell Science
Issue number6
Early online date15 Mar 2017
Publication statusPublished - 15 Mar 2017

Bibliographical note

© 2017. Published by The Company of Biologists Ltd.


  • Base Sequence
  • Cell Membrane/metabolism
  • Lipids/chemistry
  • Phosphatidylinositol 4,5-Diphosphate/metabolism
  • Phosphatidylserines/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


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