title: Sex-specific homeodomain proteins Sxi1alpha and Sxi2a coordinately regulate sexual development in Cryptococcus neoformans.
abstract: Homeodomain proteins are central regulators of development in eukaryotes. In fungi, homeodomain proteins have been shown to control cell identity and sexual development. Cryptococcus neoformans is a human fungal pathogen with a defined sexual cycle that produces spores, the suspected infectious particles. Previously, only a single homeodomain regulatory protein involved in sexual development, Sxi1alpha, had been identified. Here we present the discovery of Sxi2a, a predicted but heretofore elusive cell-type-specific homeodomain protein essential for the regulation of sexual development. Our studies reveal that Sxi2a is necessary for proper sexual development and sufficient to drive this development in otherwise haploid alpha cells. We further show that Sxi1alpha and Sxi2a interact with one another and impart similar expression patterns for two key mating genes. The discovery of Sxi2a and its relationship with Sxi1alpha leads to a new model for how the sexual cycle is controlled in C. neoformans, with implications for virulence.
authors.affiliation: Department of Molecular Genetics and Microbiology, 100 Research Dr., Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Hull
authors.forename: Marie-Josee
authors.initials: MJ
authors.lastname: Boily
authors.forename: Joseph
authors.initials: J
authors.lastname: Heitman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D003455:Cryptococcus neoformans / Q000166:cytology / Q000254:growth & development* / Q000472:pathogenicity / Q000502:physiology; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010641:Phenotype; D010675:Pheromones / Q000378:metabolism; D016415:Sequence Alignment; D020798:Two-Hybrid System Techniques
chemical_list: D005656:Fungal Proteins; D018398:Homeodomain Proteins; D010675:Pheromones