| Title: | Allelic exchange of pheromones and their receptors reprograms sexual identity in Cryptococcus neoformans |
| Author(s): | Stanton BC; Giles SS; Staudt MW; Kruzel EK; Hull CM; |
| Address: | "Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, United States of America" |
| DOI: | 10.1371/journal.pgen.1000860 |
| ISSN/ISBN: | 1553-7404 (Electronic) 1553-7390 (Print) 1553-7390 (Linking) |
| Abstract: | "Cell type specification is a fundamental process that all cells must carry out to ensure appropriate behaviors in response to environmental stimuli. In fungi, cell identity is critical for defining 'sexes' known as mating types and is controlled by components of mating type (MAT) loci. MAT-encoded genes function to define sexes via two distinct paradigms: 1) by controlling transcription of components common to both sexes, or 2) by expressing specially encoded factors (pheromones and their receptors) that differ between mating types. The human fungal pathogen Cryptococcus neoformans has two mating types (a and alpha) that are specified by an extremely unusual MAT locus. The complex architecture of this locus makes it impossible to predict which paradigm governs mating type. To identify the mechanism by which the C. neoformans sexes are determined, we created strains in which the pheromone and pheromone receptor from one mating type (a) replaced the pheromone and pheromone receptor of the other (alpha). We discovered that these 'alpha(a)' cells effectively adopt a new mating type (that of a cells); they sense and respond to alpha factor, they elicit a mating response from alpha cells, and they fuse with alpha cells. In addition, alpha(a) cells lose the alpha cell type-specific response to pheromone and do not form germ tubes, instead remaining spherical like a cells. Finally, we discovered that exogenous expression of the diploid/dikaryon-specific transcription factor Sxi2a could then promote complete sexual development in crosses between alpha and alpha(a) strains. These data reveal that cell identity in C. neoformans is controlled fully by three kinds of MAT-encoded proteins: pheromones, pheromone receptors, and homeodomain proteins. Our findings establish the mechanisms for maintenance of distinct cell types and subsequent developmental behaviors in this unusual human fungal pathogen" |
| Keywords: | "*Alleles Blotting, Northern Blotting, Southern Crosses, Genetic Cryptococcus neoformans/cytology/*genetics/*metabolism Fruiting Bodies, Fungal/cytology/metabolism Fungal Proteins/genetics/metabolism Gene Expression Regulation, Fungal Genes, Mating Type, F;" |
| Notes: | "MedlineStanton, Brynne C Giles, Steven S Staudt, Mark W Kruzel, Emilia K Hull, Christina M eng 5T32GMO3439/PHS HHS/ T32 GM007215/GM/NIGMS NIH HHS/ T32HG002760/HG/NHGRI NIH HHS/ T32 HG002760/HG/NHGRI NIH HHS/ R01 AI064287/AI/NIAID NIH HHS/ T32GM0721532/GM/NIGMS NIH HHS/ Wellcome Trust/United Kingdom Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2010/03/03 PLoS Genet. 2010 Feb 26; 6(2):e1000860. doi: 10.1371/journal.pgen.1000860" |
