ArticleEukaryotic cell2014
A Ric8/synembryn homolog promotes Gpa1 and Gpa2 activation to respectively regulate cyclic AMP and pheromone signaling in Cryptococcus neoformans.
Article in Eukaryotic cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 23 citations in OpenAlex.
- Unisexual reproduction in the global human fungal pathogenProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Unisexual reproduction in the global human fungal pathogenbioRxiv : the preprint server for biology · 2025Article
- Article
- The Cryptococcus gattii species complex: Unique pathogenic yeasts with understudied virulence mechanisms.PLoS neglected tropical diseases · 2022Review
- An in vitro method for inducing titan cells reveals novel features of yeast-to-titan switching in the human fungal pathogen Cryptococcus gattii.PLoS pathogens · 2022Article
- Epistatic genetic interactions govern morphogenesis during sexual reproduction and infection in a global human fungal pathogen.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Genetic Transformation inJournal of fungi (Basel, Switzerland) · 2021Review
- Pleiotropy and epistasis within and between signaling pathways defines the genetic architecture of fungal virulence.PLoS genetics · 2021Article
- Unisexual reproduction promotes competition for mating partners in the global human fungal pathogen Cryptococcus deneoformans.PLoS genetics · 2019Article
- 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
- The Cryptococcus neoformans Titan cell is an inducible and regulated morphotype underlying pathogenesis.PLoS pathogens · 2018Article
- Comparative genome-wide analysis of extracellular small RNAs from the mucormycosis pathogen Rhizopus delemar.Scientific reports · 2018Article
- Comparative proteomic analysis of Gib2 validating its adaptor function in Cryptococcus neoformans.PloS one · 2017Article
- A Model for Direction Sensing in Dictyostelium discoideum: Ras Activity and Symmetry Breaking Driven by a Gβγ-Mediated, Gα2-Ric8 -- Dependent Signal Transduction Network.PLoS computational biology · 2016Article
- The cAMP/protein kinase A signaling pathway in pathogenic basidiomycete fungi: Connections with iron homeostasis.Journal of microbiology (Seoul, Korea) · 2015Review
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4 authors at 3 institutions in 2 countries.
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Abstract
The G protein α subunits Gpa1, Gpa2, and Gpa3 mediate signal transduction and are important in the growth and virulence of Cryptococcus neoformans. To understand how Gpa1 functions without a conventional Gβ subunit, we characterized a resistance to inhibitors of cholinesterase 8 (Ric8) homolog from C. neoformans, which shares amino acid sequence homology with other Ric8 proteins that exhibit guanine nucleotide exchange factor (GEF) activity toward Gα. We found that the ric8 mutant was reduced in capsule size and melanin formation, which could be suppressed by cyclic AMP (cAMP) supplementation or by introducing the activated GPA1(Q284L) allele. Consistent with the fact that Ric8 participates in cAMP signaling to regulate virulence, the ric8 mutant was attenuated in virulence toward mice. Interestingly, disruption of RIC8 also resulted in opposing effects on pheromone signaling, as the ric8 mutant showed reduced mating but an enhanced ability to induce the pheromone response in the mating partner. To identify Ric8 functional mechanisms, we examined the interactions between Ric8 and the three Gα proteins. Ric8 interacted with Gpa1 and Gpa2, but not Gpa3. The presence of Gpa1(Q284L) negatively affected its interaction with Ric8, whereas the activated Gpa2(Q203L) allele abolished the interaction. Collectively, these findings suggest that Ric8 functions as a GEF to facilitate the activation of Gpa1-cAMP signaling and to promote Gpa2, affecting mating efficiency. Our study highlights the distinct and conserved characteristics associated with G protein signaling and contributes to our overall understanding of how G protein α subunits function with or without a canonical Gβ partner in C. neoformans.
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