G Proteins Spontaneous Shmooing in Saccharomyces Sans Sst2

Yeast release pheromones bind to heterotrimeric guanosine triphosphate (GTP)-binding protein (G protein)-coupled receptors (GPCRs), triggering a mating response in which cells of the opposite mating type extend a projection called a shmoo. The mating response depends on GPCR-stimulated guanine nucleotide exchange on the G protein α subunit (Gα), leading to dissociation of Gα from Gβ, and the subsequent binding of Gβ to several sets of proteins, which triggers a mitogen-activated protein kinase (MAPK) cascade, shmoo production, transcriptional activation, and cell cycle arrest. The regulator of G-protein signaling (RGS) protein Sst2 stimulates the intrinsic GTPase activity of Gα, accelerating Gα reassociation with Gβ and termination of the response. Siekhaus and Drubin observed spontaneous shmooing in yeast lacking Sst2 in the absence of mating partners or added pheromone. The authors used selective deletion of different components of yeast signaling pathways to determine that spontaneous shmooing in cells lacking Sst2 did not require any external signal or functional GPCR. Gβ and a MAPK scaffold protein, however, were required. Pathway activation in the cells lacking Sst2, as measured by transcriptional activation of a fluorescent gene reporter, was comparable to that seen in mating wild-type cells. Mutational analysis of Gα and Sst2 indicated that Sst2 activity was required to inhibit spontaneous activation of the G-protein signaling pathway.

D. E. Siekhaus, D. G. Drubin, Spontaneous receptor-independent heterotrimeric G-protein signalling in an RGS mutant. Nature Cell Biol. 5, 231-235 (2003). [Online Journal]