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Vol. 18, Issue 11, 4201-4209, November 2007
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Departments of *Pediatrics and ||Microbiology, Immunology, and Parasitology, and The Research Institute for Children, Louisiana State University Health Sciences Center, New Orleans, LA 70118
Submitted February 20, 2007;
Revised July 24, 2007;
Accepted August 7, 2007
Monitoring Editor: Daniel Lew
Perturbation of pheromone signaling modulates not only mating but also virulence in Cryptococcus neoformans, an opportunistic human pathogen known to encode three G
, one G
, and two G
subunit proteins. We have found that Gs Gpa2 and Gpa3 exhibit shared and distinct roles in regulating pheromone responses and mating. Gpa2 interacted with the pheromone receptor homolog Ste3, G subunit Gpb1, and RGS protein Crg1. Crg1 also exhibited in vitro GAP activity toward Gpa2. These findings suggest that Gpa2 regulates mating through a conserved signaling mechanism. Moreover, we found that Gs Gpg1 and Gpg2 both regulate pheromone responses and mating. gpg1 mutants were attenuated in mating, and gpg2 mutants were sterile. Finally, although gpa2, gpa3, gpg1, gpg2, and gpg1 gpg2 mutants were fully virulent, gpa2 gpa3 mutants were attenuated for virulence in a murine model. Our study reveals a conserved but distinct signaling mechanism by two G, one G, and two G proteins for pheromone responses, mating, and virulence in Cryptococcus neoformans, and it also reiterates that the link between mating and virulence is not due to mating per se but rather to certain mating-pathway components that encode additional functions promoting virulence.
The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).
Present addresses: 
University of Illinois at Chicago, 835 S. Wolcott Ave., Chicago, IL 60612;
Department of Plant Pathology, Nanjing Agricultural University, Nanjing, PRC.
Address correspondence to: Ping Wang (pwang{at}lsuhsc.edu).
Abbreviations used: GAP, GTPase-activating protein; RGS, regulator of G protein signaling.
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