Far out

Abstract

The establishment of cellular polarity is critical for a cell's morphological response to external stimuli. In budding yeast, mating pheromones trigger a pathway in which G protein βγ subunits carry the signal from activated pheromone receptors to a MAP kinase cascade leading to cell-cycle arrest, gene expression and growth of a projection towards the mating partner. Cdc24p, Cdc42p and Bem1p are involved in actin reorganization that underlies the morphological changes during mating. However, it has not been clear how these proteins are targeted to the polarization site to direct the correct orientation of the mating projection. Now, Butty et al.1 Butty A-C. et al. The role of Far1p in linking the heterotrimeric G protein to polarity establishment proteins during yeast mating. Science. 1998; 282: 1511-1516 Crossref PubMed Scopus (173) Google Scholar reveal that Far1p may provide a molecular connection between the pheromone signal and cell polarization, by simultaneously binding the Gβγ and the Cdc24p–Cdc42p– Bem1p complexes on different domains. Cells containing mutant Far1p unable to bind Gβγ or polarity-establishment proteins are unable to orientate growth towards the mating partner. In response to pheromone, Far1p moves from the nucleus to the cytoplasm even if the Cdc42p–Cdc24p–Bem1p-binding domain is deleted. This suggests that pathway activation causes relocalization of Far1p, whereupon its interaction with Gβγ brings the actin organizational machinery directly to the site of the incoming signal. Far1p is structurally similar to another Gβγ effector, the MAP kinase scaffold Ste5p, and binds Gβγ via an analogous RING finger structure. A trend is emerging in which proteins, such as Far1p and Ste5p, act as adapters enabling Gβγ to direct enzyme complexes to their site of action within the cell.