In response to different environmental stimuli, Sporothrix schenckii yeast cells, either proliferate (yeast cell cycle) or engage in a developmental program that includes proliferation accompanied by morphogenesis (yeast to mycelium transition). These responses are referred to as dimorphism, and are directly related to fungal pathogenicity. Dimorphism in S. schenckii depends on transmembrane signaling pathways that respond to cell density, external pH, temperature, extracellular calcium concentration, cyclic nucleotides and protein kinase C (PKC) effectors, such as phorbol esters. Little information exists as to how this dimorphic fungus gathers information from the environment and transduces it into an environmental signal. One of the principal recipients of external signaling in many cell types are the heterotrimeric G proteins. The long term goal of this project is to establish the role of the G proteins coupled signaling pathways in the expression of the dimorphic potential of S. schenckii. In our opinion, the most important events that regulate dimorphism in fungi are the ones that trigger the initial signaling cascade. Possibly, once this is elucidated, targets for fungal drug therapy will emerge. In this granting period we will continue our efforts in the identification and characterization of the components G protein-coupled pathways in S. schenckii in order to be able to the study their involvement in the dimorphic transitions. The experimental objectives of this work are: 1. identifying, cloning and sequencing genes encoding proteins involved in signal transduction pathways such as G-protein coupled receptor(s), alpha, beta and gamma subunits of heterotrimeric G proteins in S. schenckii, 2. disrupting these genes in order to establish their relationship to dimorphism and 3. the study of the effects on the yeast o mycelium transition and the yeast cell cycle in mutants of the different components of the G protein-coupled pathways.
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