The protein kinase Tor1 regulates adhesin gene expression in Candida albicans.
Eukaryotic cell growth is coordinated in response to nutrient availability, growth factors, and environmental stimuli, enabling cell-cell interactions that promote survival. The rapamycin-sensitive Tor1 protein kinase, which is conserved from yeasts to humans, participates in a signaling pathway central to cellular nutrient responses. To gain insight into Tor-mediated processes in human fungal pathogens, we have characterized Tor signaling in Candida albicans. Global transcriptional profiling revealed evolutionarily conserved roles for Tor1 in regulating the expression of genes involved in nitrogen starvation responses and ribosome biogenesis. Interestingly, we found that in C. albicans Tor1 plays a novel role in regulating the expression of several cell wall and hyphal specific genes, including adhesins and their transcriptional repressors Nrg1 and Tup1. In accord with this transcriptional profile, rapamycin induced extensive cellular aggregation in an adhesin-dependent fashion. Moreover, adhesin gene induction and cellular aggregation of rapamycin-treated cells were strongly dependent on the transactivators Bcr1 and Efg1. These findings support models in which Tor1 negatively controls cellular adhesion by governing the activities of Bcr1 and Efg1. Taken together, these results provide evidence that Tor1-mediated cellular adhesion might be broadly conserved among eukaryotic organisms.
Bastidas
Robert J
RJ
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, USA.
Heitman
Joseph
J
Cardenas
Maria E
ME
D002176:Candida albicans / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D002449:Cell Aggregation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D025301:Hyphae / Q000254:growth & development / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D009687:Nuclear Proteins; D019869:Phosphatidylinositol 3-Kinases; D012097:Repressor Proteins; D020123:Sirolimus; D014157:Transcription Factors; C109455:ALA1 protein, Candida albicans; C093538:ALS1 protein, Candida albicans; C113620:ALS3 protein, Candida albicans