Heterotrimeric G Protein-coupled Receptor Signaling in Yeast Mating Pheromone Response

Abstract

The DNAs encoding the receptors that respond to the peptide mating pheromones of the budding yeastSaccharomyces cerevisiaewere isolated in 1985, and were the very first genes for agonist-binding heterotrimeric G protein-coupled receptors (GPCRs) to be cloned in any organism. Now, over 30 years later, this yeast and its receptors continue to provide a pathfinding experimental paradigm for investigating GPCR-initiated signaling and its regulation, as described in this retrospective overview.

Keywords: G protein; G protein-coupled receptor (GPCR); Saccharomyces cerevisiae; adaptor protein; cell adhesion; cell cycle arrest; cell differentiation; cell fusion; gene regulation; mitogen-activated protein kinase (MAPK); morphogenesis; nuclear fusion; polarized morphogenesis; post-translational modification (PTM); protein phosphorylation; scaffold protein; signal transduction.

FIGURE 1.

Overview of the events that occur in pheromone-induced conjugation (“mating”) of the two haploid mating types of the budding yeast S. cerevisiae. Adapted from Ref. . © 2006 Cold Spring Harbor Laboratory Press.

FIGURE 2.

Schematic representation of the GPCR-initiated biochemical processes required for execution of the mating pheromone response program. For clarity, activation and roles of the ancillary MAPK Kss1 have been omitted. Whether pheromone binding causes dissociation of Ste2 dimers concomitant with GTP-for-GDP exchange in Gpa1 (Gα) and release of free Ste4-Ste18 (Gβγ) is a speculative model. See text for further details.

FIGURE 3.

Major negative feedback mechanisms promoting adaptation to pheromone signaling that act at the receptor level. See text for details. Panel D was adapted from Ref. . © 2002 Nature Publishing Group.