| Title: | A Rac homolog functions downstream of Ras1 to control hyphal differentiation and high-temperature growth in the pathogenic fungus Cryptococcus neoformans |
| Author(s): | Vallim MA; Nichols CB; Fernandes L; Cramer KL; Alspaugh JA; |
| Address: | "Department of Medicine, Duke University Medical Center (DUMC) 3355, Durham, NC 27710, USA" |
| DOI: | 10.1128/EC.4.6.1066-1078.2005 |
| ISSN/ISBN: | 1535-9778 (Print) 1535-9786 (Electronic) 1535-9786 (Linking) |
| Abstract: | "The Cryptococcus neoformans Ras1 protein serves as a central regulator for several signaling pathways. Ras1 controls the induction of the mating pheromone response cascade as well as a distinct signaling pathway that allows this pathogenic fungus to grow at human physiological temperature. To characterize elements of the Ras1-dependent high-temperature growth pathway, we performed a multicopy suppressor screen, identifying genes whose overexpression allows the ras1 mutant to grow at 37 degrees C. Using this genetic technique, we identified a C. neoformans gene encoding a Rac homolog that suppresses multiple ras1 mutant phenotypes. Deletion of the RAC1 gene does not affect high-temperature growth. However, a rac1 mutant strain demonstrates a profound defect in haploid filamentation as well as attenuated mating. In a yeast two-hybrid assay, Rac1 physically interacts with the PAK kinase Ste20, which similarly regulates hyphal formation in this fungus. Similar to Rac1, overexpression of the STE20alpha gene also restores high-temperature growth to the ras1 mutant. These results support a model in which the small G protein Rac1 acts downstream of Ras proteins and coordinately with Ste20 to control high-temperature growth and cellular differentiation in this human fungal pathogen" |
| Keywords: | "Base Sequence Cryptococcus neoformans/cytology/genetics/growth & development/pathogenicity/*physiology DNA, Fungal *Fungal Proteins Gene Expression Regulation, Fungal Genes, Fungal Genome, Fungal *Hot Temperature Hyphae/*growth & development Mutation Prot;" |
| Notes: | "MedlineVallim, Marcelo A Nichols, Connie B Fernandes, Larissa Cramer, Kari L Alspaugh, J Andrew eng T32 AI007392/AI/NIAID NIH HHS/ R01 AI050128/AI/NIAID NIH HHS/ U01 AI48594-01/AI/NIAID NIH HHS/ 5T32AI07392/AI/NIAID NIH HHS/ 1R01-AI050128/AI/NIAID NIH HHS/ AI47087/AI/NIAID NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. 2005/06/11 Eukaryot Cell. 2005 Jun; 4(6):1066-78. doi: 10.1128/EC.4.6.1066-1078.2005" |
