| Title: | Pheromones stimulate mating and differentiation via paracrine and autocrine signaling in Cryptococcus neoformans |
| Author(s): | Shen WC; Davidson RC; Cox GM; Heitman J; |
| Address: | "Department of Genetics, Duke University Medical Center, Durham, North Carolina 27710, USA" |
| DOI: | 10.1128/EC.1.3.366-377.2002 |
| ISSN/ISBN: | 1535-9778 (Print) 1535-9786 (Electronic) 1535-9786 (Linking) |
| Abstract: | "Cryptococcus neoformans is a pathogenic fungus with a defined sexual cycle involving haploid MATalpha and MATa cells. Interestingly, MATalpha strains are more common, are more virulent than congenic MATa strains, and undergo haploid fruiting in response to nitrogen limitation or MATa cells. Three genes encoding the MFalpha pheromone were identified in the MATalpha mating-type locus and shown to be transcriptionally induced by limiting nutrients and coculture with MATa cells. The MFalpha1, MFalpha2, and MFalpha3 genes were mutated, individually and in combination. MATalpha strains lacking MFalpha pheromone failed to induce morphological changes in MATa cells. Pheromoneless MATalpha mutants were fusion and mating impaired but not sterile and mated at approximately 1% the wild-type level. The pheromoneless MATalpha mutants were also partially defective in haploid fruiting, and overexpression of MFalpha pheromone enhanced haploid fruiting. Overexpression of MFa pheromone also enhanced haploid fruiting of MATalpha cells and stimulated conjugation tube formation in MATa cells. A conserved G-protein activated mitogen-activated protein kinase signaling pathway was found to be required for both induction and response to mating pheromones. The MFalpha pheromone was not essential for virulence of C. neoformans but does contribute to the overall virulence composite. These studies define paracrine and autocrine pheromone response pathways that signal mating and differentiation of this pathogenic fungus" |
| Keywords: | "Autocrine Communication Base Sequence Cell Differentiation/drug effects Conjugation, Genetic/drug effects Cryptococcus neoformans/*drug effects/genetics/pathogenicity/*physiology DNA, Fungal/genetics Gene Expression Genes, Fungal Genes, Mating Type, Funga;" |
| Notes: | "MedlineShen, Wei-Chiang Davidson, Robert C Cox, Gary M Heitman, Joseph eng R37 AI039115/AI/NIAID NIH HHS/ R01 AI042159/AI/NIAID NIH HHS/ R01 AI42159/AI/NIAID NIH HHS/ R01 AI039115/AI/NIAID NIH HHS/ R01 AI39115/AI/NIAID NIH HHS/ P01 AI44975/AI/NIAID NIH HHS/ P01 AI044975/AI/NIAID NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. 2002/11/29 Eukaryot Cell. 2002 Jun; 1(3):366-77. doi: 10.1128/EC.1.3.366-377.2002" |
