title: Conserved modular design of an oxygen sensory/signaling network with species-specific output.
abstract: Principles of modular design are evident in signaling networks that detect and integrate a given signal and, depending on the organism in which the network module is present, transduce this signal to affect different metabolic or developmental pathways. Here we report a global transcriptional analysis of an oxygen sensory/signaling network in Caulobacter crescentus consisting of the sensor histidine kinase FixL, its cognate response regulator FixJ, the transcriptional regulator FixK, and the kinase inhibitor FixT. It is known that in rhizobial bacteria these proteins form a network that regulates transcription of genes required for symbiotic nitrogen fixation, anaerobic and microaerobic respiration, and hydrogen metabolism under hypoxic conditions. We have identified a positive feedback loop in this network and present evidence that the negative feedback regulator, FixT, acts to inhibit FixL by mimicking a response regulator. Overall, the core circuit topology of the Fix network is conserved between the rhizobia and C. crescentus, a free-living aerobe that cannot fix nitrogen, respire anaerobically, or metabolize hydrogen. In C. crescentus, the Fix network is required for normal cellular growth during hypoxia and controls expression of genes encoding four distinct aerobic respiratory terminal oxidases and multiple carbon and nitrogen metabolic enzymes. Thus, the Fix network is a conserved sensory/signaling module whose transcriptional output has been adapted to the unique physiologies of C. crescentus and the nitrogen-fixing rhizobia.
authors.affiliation: Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Crosson
authors.forename: Patrick T
authors.initials: PT
authors.lastname: McGrath
authors.forename: Craig
authors.initials: C
authors.lastname: Stephens
authors.forename: Harley H
authors.initials: HH
authors.lastname: McAdams
authors.forename: Lucy
authors.initials: L
authors.lastname: Shapiro
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D016935:Caulobacter crescentus / Q000502:physiology*; D019069:Cell Respiration / Q000502:physiology*; D003001:Cloning, Molecular; D025461:Feedback, Physiological / Q000502:physiology*; D005420:Flavoproteins / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D046228:Microarray Analysis; D008969:Molecular Sequence Data; D010100:Oxygen / Q000378:metabolism*; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology*; D013057:Spectrum Analysis
chemical_list: D001426:Bacterial Proteins; D005420:Flavoproteins; D010100:Oxygen