schenckii unbudded synchronized yeast cells, either proliferate (yeast cell cycle) or engage in a developmental program that includes proliferation accompanied by morphogenesis (yeast to mycelium transition). Dimorphism in S. schenckii, depends on transmembrane signalling pathways that respond to cell density Sirtuin inhibitor [2, 3], external pH [2, 3], cyclic nucleotides [4] and extracellular calcium concentration [5]. Dimorphism is an adaptation response to changing environmental conditions. The morphology displayed by

dimorphic fungi is probably the result of the stimulation of membrane receptors by extracellular ligands. Heterotrimeric (αβγ) guanine nucleotide binding proteins have been associated with membrane receptors and with morphogenetic transition signalling in many selleck chemicals llc eukaryotes, and play a crucial role in fungal morphogenesis as well [6]. They constitute SRT1720 research buy a family of GTP hydrolases involved in signal transduction pathways. These proteins are coupled to membrane receptors (GPCR) that recognize different extracellular signals. The α subunits of the heterotrimeric G proteins bind GTP. The interaction of a ligand with the GPRC initiates the exchange of bound GDP for GTP in the Gα subunit resulting in the dissociation of the heterotrimer into α-GTP and βγ subunits. The dissociated α-GTP subunit and the βγ dimer, relay signals to different targets resulting in changes in cytoplasmic

ionic composition or in second messenger levels (e.g., cAMP) Thalidomide that ultimately lead to a cellular response [7–10]. Genes encoding proteins that are similar to the Gα class of the heterotrimeric G proteins have been described in filamentous fungi such as Aspergillus

nidulans [11] and Neurospora crassa [12–14], as well as in fungal plant pathogens like Cryphonectria parasitica [15, 16], Ustilago maydis [17] and Magnaporthe grisea [18], among others. In S. schenckii, a 41 kDa Gα subunit homologous to the Gαi subunit and sensitive to inhibition by pertussis toxin was described previously by us [19]. This was the first Gαi subunit described in a pathogenic dimorphic fungus. In higher eukaryotes, members of the Gα class are known to regulate adenylate cyclase [20], cGMP phosphodiesterase [21], phosphoinositide-3-kinase [22], calcium and potassium channels [22–24], and the activity of phospholipases [9, 25–28]. In fungi, Gα subunits have been shown to regulate adenylate cyclase, morphogenesis and pathogenicity [6, 14, 29, 30]. Most of the studies related to determining the role of the heterotrimeric G protein subunits in fungi involved the observation of the morphological effects produced in the fungus when these genes are deleted [6, 12, 14, 18]. Nevertheless, the full scope of the processes that Gα subunits regulate in fungi is still not known and interactions between these subunits and cellular proteins have seldom been reported in pathogenic fungi.