| Title: | A constitutively active GPCR governs morphogenic transitions in Cryptococcus neoformans |
| Author(s): | Hsueh YP; Xue C; Heitman J; |
| Address: | "Department of Molecular Genetics and Microbiology, Duke University, Durham, NC 27710, USA" |
| ISSN/ISBN: | 1460-2075 (Electronic) 0261-4189 (Print) 0261-4189 (Linking) |
| Abstract: | "Sex in fungi is driven by peptide pheromones sensed through seven-transmembrane pheromone receptors. In Cryptococcus neoformans, sexual reproduction occurs through an outcrossing/heterothallic a- sexual cycle or an inbreeding/homothallic - unisexual mating process. Pheromone receptors encoded by the mating-type locus (MAT) mediate reciprocal pheromone sensing during opposite-sex mating and contribute to but are not essential for unisexual mating. A pheromone receptor-like gene, CPR2, was discovered that is not encoded by MAT and whose expression is induced during a- mating. cpr2 mutants are fertile but have a fusion defect and produce abnormal hyphal structures, whereas CPR2 overexpression elicits unisexual reproduction. When heterologously expressed in Saccharomyces cerevisiae, Cpr2 activates pheromone responses in the absence of any ligand. This constitutive activity results from an unconventional residue, Leu(222), in place of a conserved proline in transmembrane domain six; a Cpr2(L222P) mutant is no longer constitutively active. Cpr2 engages the same G-protein activated signalling cascade as the Ste3a/alpha pheromone receptors, and thereby competes for pathway activation. This study established a new paradigm in which a naturally occurring constitutively active G protein-coupled receptor governs morphogenesis in fungi" |
| Keywords: | "Blotting, Northern Cryptococcus neoformans/genetics/*metabolism/*ultrastructure Fungal Proteins/genetics/metabolism/*physiology Gene Expression Regulation, Fungal Immunoblotting Microscopy, Electron, Scanning Models, Biological Pheromones/metabolism Prote;" |
| Notes: | "MedlineHsueh, Yen-Ping Xue, Chaoyang Heitman, Joseph eng R01 AI039115/AI/NIAID NIH HHS/ R21 AI070230/AI/NIAID NIH HHS/ R37 AI039115/AI/NIAID NIH HHS/ R01 AI39115/AI/NIAID NIH HHS/ Research Support, N.I.H., Extramural England 2009/03/27 EMBO J. 2009 May 6; 28(9):1220-33. doi: 10.1038/emboj.2009.68. Epub 2009 Mar 26" |
