| Title: | Epigenetic control of pheromone MAPK signaling determines sexual fecundity in Candida albicans |
| Author(s): | Scaduto CM; Kabrawala S; Thomson GJ; Scheving W; Ly A; Anderson MZ; Whiteway M; Bennett RJ; |
| Address: | "Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912. Department of Biology, Concordia University, Montreal, QC, Canada H4B 1R6. Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912; Richard_Bennett@brown.edu" |
| ISSN/ISBN: | 1091-6490 (Electronic) 0027-8424 (Print) 0027-8424 (Linking) |
| Abstract: | "Several pathogenic Candida species are capable of heritable and reversible switching between two epigenetic states, 'white' and 'opaque.' In Candida albicans, white cells are essentially sterile, whereas opaque cells are mating-proficient. Here, we interrogate the mechanism by which the white-opaque switch regulates sexual fecundity and identify four genes in the pheromone MAPK pathway that are expressed at significantly higher levels in opaque cells than in white cells. These genes encode the beta subunit of the G-protein complex (STE4), the pheromone MAPK scaffold (CST5), and the two terminal MAP kinases (CEK1/CEK2). To define the contribution of each factor to mating, C. albicans white cells were reverse-engineered to express elevated, opaque-like levels of these factors, either singly or in combination. We show that white cells co-overexpressing STE4, CST5, and CEK2 undergo mating four orders of magnitude more efficiently than control white cells and at a frequency approaching that of opaque cells. Moreover, engineered white cells recapitulate the transcriptional and morphological responses of opaque cells to pheromone. These results therefore reveal multiple bottlenecks in pheromone MAPK signaling in white cells and that alleviation of these bottlenecks enables efficient mating by these 'sterile' cell types. Taken together, our findings establish that differential expression of several MAPK factors underlies the epigenetic control of mating in C. albicans We also discuss how fitness advantages could have driven the evolution of a toggle switch to regulate sexual reproduction in pathogenic Candida species" |
| Keywords: | "Candida albicans/genetics/*metabolism Epigenesis, Genetic/*physiology Gene Expression Regulation, Fungal/*physiology MAP Kinase Signaling System/*physiology Pheromones/genetics/*metabolism mating phenotypic switching sexual reproduction signaling bottlene;" |
| Notes: | "MedlineScaduto, Christine M Kabrawala, Shail Thomson, Gregory J Scheving, William Ly, Andy Anderson, Matthew Z Whiteway, Malcolm Bennett, Richard J eng F31 DE024036/DE/NIDCR NIH HHS/ R01 AI081704/AI/NIAID NIH HHS/ R21 AI122011/AI/NIAID NIH HHS/ T32 GM007601/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2017/12/20 Proc Natl Acad Sci U S A. 2017 Dec 26; 114(52):13780-13785. doi: 10.1073/pnas.1711141115. Epub 2017 Dec 18" |
