Mechanisms for Controlling Cell Polarity in Yeast

Abstract

Cell polarity is critical for essential functions in many types of cells. Rho-family GTPases are master regulators of cell polarity. Thus, mechanisms for controlling the activity of Rho GTPases are of both academic interest and practical concern. While much has been discovered about regulation of Rho GTPase activity by partners like GEFs, GAPs, and GDIs, there are still many things which remain unclear about how their behavior is enforced in cells of various kinds.The budding yeast, Saccharomyces cerevisiae, has long been a model for studying cell polarity. Its Rho GTPase Cdc42 is responsible for defining a single polarity site for the purpose of either mating with a single partner or making a single bud. Other types of yeasts, however, can generate multiple polarity sites utilizing the same core polarity machinery. What are the rules which allow for such differences in behavior while using a similar set of proteins? We highlight key design principles established in mathematical models for Rho GTPase polarity machineries and show that they apply in budding yeast cells: strains featuring specific genetic perturbations which increase the total amount of polarity proteins can go from making one bud, to making multiple buds.Bud emergence in yeast is enabled by cell cycle activity in G1. It is known that bud emergence also requires cytoskeletal changes which are orchestrated by Cdc42 and its effectors. How are these changes coordinated with cell cycle progression? It seems likely that G1 CDK activity regulates many aspects of Cdc42 polarization. We use live-cell fluorescence microscopy to reveal one such avenue whereby input from the cell cycle is required for many Cdc42 effector proteins to localize to sites with active Cdc42, thus restricting bud formation until the time is right.