In budding yeast, the p21-activated kinase (PAK) Ste20 regulates various aspects of cell polarity during vegetative growth, mating and filamentous growth. However, the molecular mechanisms that underlie this are unclear. Now, on , Thomas Höfken and colleagues report that several proteins involved in sterol synthesis interact with Ste20 to regulate cell polarity. To screen for Ste20 interactors, they used the split-ubiquitin system. In this, interacting proteins fused to the N- and C-terminal halves of ubiquitin bring these inactive pieces together, which allows cleavage of a linked reporter protein The screen reveals that Erg4, Cbr1 and Ncp1 (all of which are involved in the later stages of sterol synthesis in yeast) interact with Ste20. The authors then use genetic approaches to demonstrate that these proteins, like Ste20, are required for budding, cell wall assembly, mating and invasive growth. The authors propose, therefore, that sterol synthesis is crucial for cell polarization in yeast, a regulatory link likely to be conserved in higher eukaryotes.
