title: A Ras1-Cdc24 signal transduction pathway mediates thermotolerance in the fungal pathogen Cryptococcus neoformans.
abstract: Pathogenic microorganisms must precisely regulate morphogenesis to survive and proliferate within an infected host. This regulation is often controlled by conserved signal transduction pathways that direct morphological changes in varied species. One such pathway, whose components include Ras proteins and the PAK kinase Ste20, allows the human fungal pathogen Cryptococcus neoformans to grow at high temperature. Previously, we found that Ras1 signalling is required for differentiation, thermotolerance and pathogenesis in C. neoformans. We show here that the guanine nucleotide exchange factor Cdc24 is a Ras1 effector in C. neoformans to mediate the ability of this fungus to grow at high temperature and to cause disease. In addition, we provide evidence that the Ras1-Cdc24 signalling cascade functions specifically through one of the three Cdc42/Rac1 homologues in C. neoformans. In conclusion, our studies illustrate how components of conserved signalling cascades can be specialized for different downstream functions, such as pathogenesis.
authors.affiliation: Department of Medicine, Duke University Medical CenterDurham, NC 27710, USA.
authors.forename: Connie B
authors.initials: CB
authors.lastname: Nichols
authors.forename: Zahra H
authors.initials: ZH
authors.lastname: Perfect
authors.forename: J Andrew
authors.initials: JA
authors.lastname: Alspaugh
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D016764:Cell Polarity; D003453:Cryptococcosis / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000472:pathogenicity / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D015966:Gene Expression Regulation, Fungal; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000382:microbiology; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013154:Spleen / Q000382:microbiology; D013696:Temperature; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D020662:Guanine Nucleotide Exchange Factors; D017346:Protein Serine-Threonine Kinases; D020764:cdc42 GTP-Binding Protein; D018631:ras Proteins