Eukaryotic Cell
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EC Accepts, published online ahead of print on 25 July 2008
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Eukaryotic Cell doi:10.1128/EC.00077-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Heterotrimeric G protein subunit function in Candida albicans: both the {alpha} and {beta} subunits of the pheromone response G protein are required for mating

Daniel Dignard, Dominique André, and Malcolm Whiteway*

NRC Biotechnology Research Institute, 6100 Royalmount Ave., Montreal, Quebec, Canada H4P 2R2; Department of Biology, McGill University, Montreal, Quebec, Canada

* To whom correspondence should be addressed. Email: malcolm.whiteway{at}cnrc-nrc.gc.ca.


   Abstract

A pheromone-mediated signaling pathway that couples 7-transmembrane spanning receptors to a MAP kinase module controls Candida albicans mating. 7-TMD receptors are typically connected to heterotrimeric G proteins whose activation regulates downstream effectors. There have been 2 G{alpha} subunits identified in this fungal pathogen, 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{alpha} subunit in S. cerevisiae, and Gpa2p was shown to have a role in the regulation of cAMP signaling in C. albicans and to repress pheromone-mediated arrest. Here we show that disruption of CAG1 prevents mating, inactivates pheromone-mediated arrest and morphological changes, and blocks pheromone-mediated gene expression changes in opaque cells of C. albicans, while overproduction of CAG1 suppresses the hyperactive cell cycle arrest exhibited by sst2 mutant cells. Because disruption of the STE4 homolog encoding the only C. albicans gene for a heterotrimeric G{beta} subunit also blocks mating and pheromone response, it appears that in this fungal pathogen the G{alpha} and G{beta} subunits do not act antagonistically, but instead are both required for transmission of the mating signal.







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