Activation of polarized cell growth by inhibition of cell polarity

A key feature of cells is the capacity to activate new functional polarized domains contemporaneously to pre-existing ones. How cells accomplish this is not clear. Here, we show that in fission yeast inhibition of cell polarity at pre-existing domains of polarized cell growth is required to activate new growth. This inhibition is mediated by the ERM-related polarity factor Tea3, which antagonizes the activation of the Rho-GTPase Cdc42 by its co-factor Scd2. We demonstrate that Tea3 acts in a phosphorylation-dependent manner controlled by the PAK kinase Shk1 and that, like Scd2, Tea3 is direct substrate of Shk1. Importantly, we show that Tea3 and Scd2 compete for their binding to Shk1, indicating that their biochemical competition for Shk1 underpins their antagonistic roles in controlling polarity. Thus, by preventing pre-existing growth domains from becoming overpowering, Tea3 allows cells to redistribute their polarity-activating machinery to prospective sites and control their timing of activation.