文章基本信息

标题：Epigenetic control of pheromone MAPK signaling determines sexual fecundity in Candida albicans
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作者：Christine M. Scaduto ; Shail Kabrawala ; Gregory J. Thomson 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2017
卷号：114
期号：52
页码：13780-13785
DOI：10.1073/pnas.1711141115
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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 β 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.
关键词：mating ; sexual reproduction ; signaling bottlenecks ; transcriptional regulation ; phenotypic switching