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MBC in Press, published online ahead of print June 20, 2007
Mol. Biol. Cell 10.1091/mbc.E07-02-0133

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Submitted on February 16, 2007
Revised on June 5, 2007
Accepted on June 12, 2007

G Protein Signaling Governing Cell Fate Decisions Involves Opposing G{alpha} Subunits in Cryptococcus neoformans

Yen-Ping Hsueh, Chaoyang Xue, and Joseph Heitman

Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710

Monitoring Editor: Charles Boone

Communication between cells and their environments is often mediated by G protein-coupled receptors (GPCR) and cognate G proteins. In fungi, one such signaling cascade is the mating pathway triggered by pheromone/pheromone receptor recognition. Unlike S. cerevisiae, which expresses two G{alpha} subunits, most filamentous ascomycetes and basidiomycetes have three G{alpha} subunits. Previous studies have defined the G{alpha} subunit acting upstream of the cAMP-PKA pathway, but it has been unclear which G{alpha} subunit is coupled to the pheromone receptor and response pathway. Here we report that in pathogenic basidiomycetous yeast Cryptococcus neoformans, two G{alpha} subunits (Gpa2, Gpa3) sense pheromone and govern mating. gpa2 gpa3 double mutants, but neither gpa2 nor gpa3 single mutants, are sterile in bilateral cross-es. By contrast, deletion of GPA3 (but not GPA2) constitutively activates pheromone response and filamentation. Expression of GPA2 and GPA3 is differentially regulated: GPA3 expression is induced by nutrient-limitation whereas GPA2 is induced during mating. Based on the phenotype of dominant active alleles, Gpa2 and Gpa3 signal in opposition: Gpa2 promotes mating while Gpa3 inhibits. The incorporation of an additional G{alpha} into the regulatory circuit enabled increased signaling complexity and facilitated cell fate decisions involving choice between yeast growth and filamentous asexual/sexual development.

Address correspondence to: Joseph Heitman (heitm001{at}duke.edu)




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