Yeast assays for G-protein-coupled receptors

Yeast assays for G-protein-coupled receptors have many attractions due to their simplicity, low cost, and lack of endogenous receptors. Since the first report of functional coupling of the human beta2 adrenergic receptor to the yeast pheromone-response pathway in 1990, the technology has developed to a point at which more than 30 heterologous; GPCRs are now published to couple. Major breakthroughs have come from an understanding of receptor-G protein interactions, alongside advances in knowledge of the structure of heterotrimeric G proteins. Yeast screens have been used to identify ligands both from compound collections and through the autocrine expression of peptide libraries. Yeast genetics has also been applied to a functional analysis of GPCRs and peptide ligands. In this review we describe the historical development of yeast GPCR assay systems and their current applications.