Ambient pH gene regulation in fungi: making connections

Many fungi grow over a wide pH range and their gene expression is tailored to the environmental pH. In Aspergillus nidulans, the transcription factor PacC, an activator of genes expressed in alkaline conditions and a repressor of those expressed in acidic conditions, undergoes two processing proteolyses, the first being pH-signal dependent and the second proteasomal. Signal transduction involves a ‘go-between’ connecting two complexes, one of which comprises two plasma membrane proteins and an arrestin and the other comprises PacC, a cysteine protease, a scaffold and endosomal components. The Saccharomyces cerevisiae PacC orthologue, Rim101p, differs in that it does not undergo the second round of proteolysis and it functions directly as a repressor only. PacC/Rim101-mediated pH regulation is crucial to fungal pathogenicity. Many fungi grow over a wide pH range and their gene expression is tailored to the environmental pH. In Aspergillus nidulans, the transcription factor PacC, an activator of genes expressed in alkaline conditions and a repressor of those expressed in acidic conditions, undergoes two processing proteolyses, the first being pH-signal dependent and the second proteasomal. Signal transduction involves a ‘go-between’ connecting two complexes, one of which comprises two plasma membrane proteins and an arrestin and the other comprises PacC, a cysteine protease, a scaffold and endosomal components. The Saccharomyces cerevisiae PacC orthologue, Rim101p, differs in that it does not undergo the second round of proteolysis and it functions directly as a repressor only. PacC/Rim101-mediated pH regulation is crucial to fungal pathogenicity. cytosolic protein that binds to a 7-TMD receptor to down-regulate or to promote downstream signalling. Ca2+-dependent cysteine protease. Ca2+-dependent transmembrane proteins with important roles in cell adhesion. membrane compartment that receives traffic from the plasma membrane. endosomal sorting complex required for transport; each of the four protein complexes, numbered −0, I, II and III, are located on endosomal membranes, where they mediate the sorting of membrane protein cargoes in vesicles that bud into the endosomal lumen. a membrane organelle that receives membranes from the endoplasmic reticulum and delivers biosynthetic traffic to endosomes and to the plasma membrane. guanine-nucleotide-binding proteins, consisting of Gα, Gβ and Gγ subunits, which transduce the signals received by 7-transmembrane domain (TMD) receptors. The GDP-loaded heterotrimer is inactive. 7-TMD-receptor activation promotes exchange of GDP by GTP, which results in the dissociation of Gα from Gβγ with subsequent engagement of downstream effectors to the dissociated partners. the distal protein kinase in certain signal-transduction pathway phosphorylation cascades. It relays signals from activated plasma membrane receptors, usually by phosphorylating a transcription factor. thousands of DNA sequences (e. g. representing the genome) in a miniaturized array on solid substrates such as glass slides. protein domain composed of a three-helix bundle that binds to certain ESCRT-III proteins. a class of endosome, sometimes called multivesicular endosome (MVE), the lumen of which contains vesicles that originated from inward budding of the endosomal membrane. devoid of, or deficient in, neutrophils, a type of white blood cell. a membrane compartment that shares aspects of both Golgi and endosomal compartments. multi-chambered, multi-protein complex functioning in partial or complete degradation of ubiquitylated proteins. Ca2+-dependent enzyme that catalyses the phosphorylation of certain proteins and thus regulates a number of physiological functions. a class of endosomal compartment described in S. cerevisiae that receives biosynthetic membrane traffic from the Golgi and endocytic traffic from upstream endosomal compartments. iron-chelating molecules produced by various organisms to overcome the problem of low solubility of Fe3+. soluble NSF (N-ethylmaleimide-sensitive fusion protein)-attachment protein receptor proteins; SNAREs catalyse membrane fusion by forming a four-helix bundle. t-SNAREs are present in the ‘target’ acceptor membrane in heterotypic membrane fusion events. v-SNAREs are present in the ‘donor’ membrane in heterotypic membrane fusion events. covalent attachment of ubiquitin, a 76-residue polypeptide, in either a monomeric or polymeric form, functioning as a sorting or degradation signal. the capacity to cause disease. Certain mutations can render a pathogen avirulent. a category of zinc-containing DNA-binding (or occasionally protein-interacting) motif, in which four nearby cysteine or cysteine and histidine residues in a protein chelate a zinc ion.