Faculté des sciences

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

Hatakeyama, Riko ; Kono, Keiko ; Yoshida, Satoshi

In: J Cell Sci, 2017, p. jcs.198382

The plasma membrane (PM) is frequently challenged by mechanical stresses. In budding yeast, TORC2-Ypk1/Ypk2 kinase cascade plays a critical 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... More

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    Summary
    The plasma membrane (PM) is frequently challenged by mechanical stresses. In budding yeast, TORC2-Ypk1/Ypk2 kinase cascade plays a critical 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 (PS). Genetic evidence suggests that this process is mediated by the Lem3-containing lipid flippase. We propose that TORC2-Ypk1/Ypk2-Lem3 axis-mediated lipid remodelling 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 in a normal condition. Since all the signaling molecules studied here are conserved in higher eukaryotes, our findings may represent a general mechanism to cope with PM stress.