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.
| Rijpma, Sanna R; van der Velden, Maarten; González-Pons, Maria et al. (2016) Multidrug ATP-binding cassette transporters are essential for hepatic development of Plasmodium sporozoites. Cell Microbiol 18:369-83 |
| Padín-Irizarry, Vivian; Colón-Lorenzo, Emilee E; Vega-Rodríguez, Joel et al. (2016) Glutathione-deficient Plasmodium berghei parasites exhibit growth delay and nuclear DNA damage. Free Radic Biol Med 95:43-54 |
| Jardón, Javier; Izquierdo, Natalio J; Renta, Jessica Y et al. (2016) Ocular Findings in Patients with the Hermansky-Pudlak Syndrome (Types 1 and 3). Ophthalmic Genet 37:89-94 |
| Rivera-Peña, Bianca; Ruíz-Fullana, Francisco J; Vélez-Reyes, Germán L et al. (2016) HPV-16 infection modifies overall survival of Puerto Rican HNSCC patients. Infect Agent Cancer 11:47 |
| Velásquez-Martínez, Maria C; Vázquez-Torres, Rafael; Rojas, Legier V et al. (2015) Alpha-1 adrenoreceptors modulate GABA release onto ventral tegmental area dopamine neurons. Neuropharmacology 88:110-21 |
| Vega-Rodríguez, Joel; Pastrana-Mena, Rebecca; Crespo-Lladó, Keila N et al. (2015) Implications of Glutathione Levels in the Plasmodium berghei Response to Chloroquine and Artemisinin. PLoS One 10:e0128212 |
| Zenón, Frances; Cantres-Rosario, Yisel; Adiga, Radhika et al. (2015) HIV-infected microglia mediate cathepsin B-induced neurotoxicity. J Neurovirol 21:544-58 |
| Hodakoski, Cindy; Hopkins, Benjamin D; Barrows, Douglas et al. (2014) Regulation of PTEN inhibition by the pleckstrin homology domain of P-REX2 during insulin signaling and glucose homeostasis. Proc Natl Acad Sci U S A 111:155-60 |
| Jezzini, Sami H; Reyes-Colón, Dalynés; Sosa, María A (2014) Characterization of a prawn OA/TA receptor in Xenopus oocytes suggests functional selectivity between octopamine and tyramine. PLoS One 9:e111314 |
| Segarra, Annabell C; Torres-Díaz, Yvonne M; Silva, Richard D et al. (2014) Estrogen receptors mediate estradiol's effect on sensitization and CPP to cocaine in female rats: role of contextual cues. Horm Behav 65:77-87 |
Showing the most recent 10 out of 174 publications
