The GTPase Rho1 can spur a yeast cell to grow or to repair damage and resist stress. Jonasson et al. reveal how Rho1 switches between these different roles.
When conditions are good, Rho1 promotes cell growth and budding. It stimulates the synthesis of glucan, a building block of the cell wall. When the cell wall is damaged, Rho1 activates Pkc1 and switches on the cell wall integrity pathway, which curbs growth and turns on genes that repair the injury and protect the cell from stress.
To determine how Rho1 changes its function, Jonasson et al. screened for proteins that enable cells to survive the loss of three Rho1 activators. The researchers identified the protein Cdc55, which forms the regulatory portion of the PP2A phosphatase. The PP2A–Cdc55 complex hooks up with Rho1 and two other proteins, Zds1 and Zds2, at the bud cortex.
Jonasson et al. found that the PP2A–Cdc55 complex targets two RhoGAPs, Lrg1 and Sac7, that control Rho1’s activity. Lrg1 blocks glucan synthesis, whereas Sac7 prevents Pkc1 activation. PP2A–Cdc55 inhibited Lrg1 but stabilized Sac7, thus suppressing the cell wall integrity pathway while permitting growth. After cell wall damage, however, activated Pkc1 dislodged PP2A–Cdc55 from the cortex. Rho1’s function therefore depends on whether it binds to Pkc1 or the PP2A–Cdc55 complex, but researchers still need to figure out how Rho1 makes that choice.