Heterotrimeric G-Protein Subunit Function in Candida albicans : both the α and β Subunits of the Pheromone Response G Protein Are Required for Mating

A pheromone-mediated signaling pathway that couples seven-transmembrane-domain (7-TMD) receptors to a mitogen-activated protein kinase module controlsCandida albicans mating. 7-TMD receptors are typically connected to heterotrimeric G proteins whose activation regulates downstream effectors. Two Gα subunits inC. albicans have been identified previously, both of which have been implicated in aspects of pheromone response. Cag1p was found to complement the mating pathway function of the pheromone receptor-coupled Gα subunit inSaccharomyces cerevisiae , and Gpa2p was shown to have a role in the regulation of cyclic AMP signaling inC. albicans and to repress pheromone-mediated arrest. Here, we show that the disruption ofCAG1 prevented mating, inactivated pheromone-mediated arrest and morphological changes, and blocked pheromone-mediated gene expression changes in opaque cells ofC. albicans and that the overproduction ofCAG1 suppressed the hyperactive cell cycle arrest exhibited bysst2 mutant cells. Because the disruption of theSTE4 homolog constituting the onlyC. albicans gene for a heterotrimeric Gβ subunit also blocked mating and pheromone response, it appears that in this fungal pathogen the Gα and Gβ subunits do not act antagonistically but, instead, are both required for the transmission of the mating signal.