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Mol Microbiol

Title:		The RGS protein Crg2 regulates both pheromone and cAMP signalling in Cryptococcus neoformans
Author(s):		Xue C; Hsueh YP; Chen L; Heitman J;
Address:		"Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA"
Journal Title:		Mol Microbiol
Year:		2008
Volume:		20080827
Issue:		2
Page Number:		379 - 395
DOI:		10.1111/j.1365-2958.2008.06417.x
ISSN/ISBN:		1365-2958 (Electronic) 0950-382X (Print) 0950-382X (Linking)
Abstract:		"G proteins orchestrate critical cellular functions by transducing extracellular signals into internal signals and controlling cellular responses to environmental cues. G proteins typically function as switches that are activated by G protein-coupled receptors (GPCRs) and negatively controlled by regulator of G protein signalling (RGS) proteins. In the human fungal pathogen Cryptococcus neoformans, three G protein alpha subunits (Gpa1, Gpa2 and Gpa3) have been identified. In a previous study, we identified the RGS protein Crg2 involved in regulating the pheromone response pathway through Gpa2 and Gpa3. In this study, a role for Crg2 was established in the Gpa1-cAMP signalling pathway that governs mating and virulence. We show that Crg2 physically interacts with Gpa1 and crg2 mutations increase cAMP production. crg2 mutations also enhance mating filament hyphae production, but reduce cell-cell fusion and sporulation efficiency during mating. Although crg2 mutations and the Gpa1 dominant active allele GPA1(Q284L) enhanced melanin production under normally repressive conditions, virulence was attenuated in a murine model. We conclude that Crg2 participates in controlling both Gpa1-cAMP-virulence and pheromone-mating signalling cascades and hypothesize it may serve as a molecular interface between these two central signalling conduits"
Keywords:		"Animals Cryptococcosis/microbiology Cryptococcus neoformans/*physiology Cyclic AMP/*metabolism Fungal Proteins/genetics/*metabolism Hyphae/growth & development Mice Mutation, Missense Pheromones/*metabolism Protein Binding RGS Proteins/genetics/*metabolis;"
Notes:		"MedlineXue, Chaoyang Hsueh, Yen-Ping Chen, Lydia Heitman, Joseph eng R37 AI039115/AI/NIAID NIH HHS/ R21 AI070230/AI/NIAID NIH HHS/ R01 AI039115/AI/NIAID NIH HHS/ R01 AI39115/AI/NIAID NIH HHS/ R37 AI039115-15/AI/NIAID NIH HHS/ Research Support, N.I.H., Extramural England 2008/09/03 Mol Microbiol. 2008 Oct; 70(2):379-95. doi: 10.1111/j.1365-2958.2008.06417.x. Epub 2008 Aug 27"