Interaction fidelity in two-component signaling.
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ABSTRACT:
SUBMITTER: Szurmant H
PROVIDER: S-EPMC2847666 | biostudies-literature | 2010 Apr
REPOSITORIES: biostudies-literature
Publications
Interaction fidelity in two-component signaling.
Szurmant Hendrik H Hoch James A JA
Current opinion in microbiology 20100203 2
Two component signal transduction systems and phosphorelays have been adapted and amplified by bacteria to respond to a multitude of environmental, metabolic and cell cycle signals while maintaining essentially identical structures for the domains responsible for recognition and phosphotransfer between the sensor histidine kinase and the response regulator. Co-crystal structures of these domains have revealed the variable residues at the interaction surface of the two components responsible for ...[more]
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Project description:Two-component signal transduction pathways are one of the primary means by which microorganisms respond to environmental signals. These signaling cascades originated in prokaryotes and were inherited by eukaryotes via endosymbiotic lateral gene transfer from ancestral cyanobacteria. We report here that the nuclear genome of pathogenic fungus Candida albicans contains elements of a two-component signaling pathway that seem to be targeted to the mitochondria. In C. albicans two-component response regulator protein Srr1(Stress Response Regulator) contains a mitochondrial targeting sequence at the N-terminus, and fluorescence microscopy reveals mitochondrial localization of GFP-tagged Srr1p. Moreover, phylogenetic analysis indicates that C. albicans Srr1p is more closely related to histidine kinases and response regulators found in marine bacteria compared to other two-component proteins present in the fungi. These data suggest conservation of this protein during the evolutionary transition from endosymbiont to a subcellular organelle. We used microarray analysis to determine if the phenotypes observed with srr1M-NM-^T/M-NM-^T mutant could be correlated with gene transcriptional changes. Expression of mitochondrial genes was altered in the srr1M-NM-^T/M-NM-^T null mutant in comparison to the wild type. Furthermore, apoptosis significantly increased in the srr1M-NM-^T/M-NM-^T mutant strain compared to wild type, suggesting activation of mitochondria dependent apoptotic cell death pathway in the srr1M-NM-^T/M-NM-^T mutant. This study shows for the first time that a lower eukaryote like C. albicans possesses a two-component response regulator protein that has survived in mitochondria and regulates a subset of genes whose functions are associated with oxidative stress response and programmed cell death (apoptosis). Candida albicans wildtype or srr1 null cells were left untreated or were treated with either 8mM H2O2 for one hour prior to RNA isolation.
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