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

Received 29 February 2008/Accepted 15 July 2008 A pheromone-mediated signaling pathway that couples seven-transmembrane-domain (7-TMD) receptors to a mitogen-activated protein kinase module controls Candida albicans mating. 7-TMD receptors are typically connected to heterotrimeric G proteins whose activation regulates downstream effectors. Two G subunits in C. 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 G subunit in Saccharomyces cerevisiae, and Gpa2p was shown to have a role in the regulation of cyclic AMP signaling in C. albicans and to repress pheromone-mediated arrest. Here, we show that the disruption of CAG1 prevented mating, inactivated pheromone-mediated arrest and morphological changes, and blocked pheromone-mediated gene expression changes in opaque cells of C. albicans and that the overproduction of CAG1 suppressed the hyperactive cell cycle arrest exhibited by sst2 mutant cells. Because the disruption of the STE4 homolog constituting the only C. albicans gene for a heterotrimeric G subunit also blocked mating and pheromone response, it appears that in this fungal pathogen the G and G subunits do not act antagonistically but, instead, are both required for the transmission of the mating signal. Many fungi have well-defined mating systems. Currently, the most thoroughly studied is that of the baker’s or brewer’s yeast Saccharomyces cerevisiae (2, 12). In this yeast, a signaling pathway