ArticleEukaryotic cell2008
The RGS protein Crg2 regulates pheromone and cyclic AMP signaling in Cryptococcus neoformans.
Article in Eukaryotic cell, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 39 citations in OpenAlex.
- Genetic Transformation inJournal of fungi (Basel, Switzerland) · 2021Review
- The cAMP/Protein Kinase a Pathway Regulates Virulence and Adaptation to Host Conditions inFrontiers in cellular and infection microbiology · 2019Review
- Investigation of Cryptococcus neoformans magnesium transporters reveals important role of vacuolar magnesium transporter in regulating fungal virulence factors.MicrobiologyOpen · 2018Article
- Proteome analysis reveals global response to deletion of mrflbA in Monascus ruber.Journal of microbiology (Seoul, Korea) · 2018Article
- Article
- Comparative Ecology of CapsularFrontiers in microbiology · 2017Article
- Masking the Pathogen: Evolutionary Strategies of Fungi and Their Bacterial Counterparts.Journal of fungi (Basel, Switzerland) · 2015Review
- A Ric8/synembryn homolog promotes Gpa1 and Gpa2 activation to respectively regulate cyclic AMP and pheromone signaling in Cryptococcus neoformans.Eukaryotic cell · 2014Article
- Article
- Noncanonical Gβ Gib2 is a scaffolding protein promoting cAMP signaling through functions of Ras1 and Cac1 proteins in Cryptococcus neoformans.The Journal of biological chemistry · 2014Article
- Cryptococcus neoformans hyperfilamentous strain is hypervirulent in a murine model of cryptococcal meningoencephalitis.PloS one · 2014Article
- Aimless mutants of Cryptococcus neoformans: failure to disseminate.Fungal biology reviews · 2012Article
- The Cryptococcus neoformans capsule: a sword and a shield.Clinical microbiology reviews · 2012Review
- 'Popping the clutch': novel mechanisms regulating sexual development in Cryptococcus neoformans.Mycopathologia · 2012Review
- Structure-function analysis of Rgs1 in Magnaporthe oryzae: role of DEP domains in subcellular targeting.PloS one · 2012Article
- Profiling a killer, the development of Cryptococcus neoformans.FEMS microbiology reviews · 2012Review
- Regulatory circuitry governing fungal development, drug resistance, and disease.Microbiology and molecular biology reviews : MMBR · 2011Review
- The RGS protein Crg2 is required for establishment and progression of murine pulmonary cryptococcosis.Medical mycology · 2011Article
- Pleiotropic function of intersectin homologue Cin1 in Cryptococcus neoformans.Molecular microbiology · 2010Article
- Comparative transcriptome analysis reveals novel roles of the Ras and cyclic AMP signaling pathways in environmental stress response and antifungal drug sensitivity in Cryptococcus neoformans.Eukaryotic cell · 2010Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Crg1 and Crg2 are regulators of G-protein signaling homologs found in the human fungal pathogen Cryptococcus neoformans. Crg1 negatively regulates pheromone responses and mating through direct inhibition of Galpha subunits Gpa2 and Gpa3. It has also been proposed that Crg2 has a role in mating, as genetic crosses involving Deltacrg2 mutants resulted in formation of hyperfilaments. We found that mutation of Gpa2 and Gpa3 partially suppressed the hyperfilamentation, mutation of Gpa3 alleviated Deltacrg2-specfic cell swelling, and mutation of the mitogen-activated protein kinase Cpk1 blocked both processes. These findings indicate that Gpa2 and Gpa3 function downstream of Crg2 and that Gpa3 is also epistatic to Crg2 in a Cpk1-dependent morphogenesis process linked to mating. Significantly, we found that Deltacrg2 mutants formed enlarged capsules that mimic cells expressing a constitutively active GPA1(Q284L) allele and that the levels of intracellular cyclic AMP (cAMP) were also elevated, suggesting that Crg2 also negatively regulates the Gpa1-cAMP signaling pathway. We further showed that Crg2 interacted with Gpa3 and Gpa1, but not Gpa2, in a pulldown assay and that Crg2 maintained a higher in vitro GTPase-activating protein activity toward Gpa3 and Gpa1 than to Gpa2. Finally, we found that dysregulation of cAMP due to the Crg2 mutation attenuated virulence in a murine model of cryptococcosis. Taken together, our study reveals Crg2 as an RGS (regulator of G-protein signaling) protein of multiregulatory function, including one that controls mating distinctly from Crg1 and one that serves as a novel inhibitor of Gpa1-cAMP signaling.
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