The involvement of transport proteins in transcriptional and metabolic regulation

Västermark, Åke; Saier, Milton H.

doi:10.1016/j.mib.2014.01.002

Cited by 48 publications

(37 citation statements)

References 50 publications

(41 reference statements)

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“…The two dedicated proteins work in a coordinated manner to ensure that expression of transporters is specifically induced by the presence of nutrients in the extracellular environment. Transporters can participate in nutrient sensing via intramembrane protein-protein interactions with the sensor kinase (54). This has been documented in bacteria, such as for the transporter and kinase genes dctA and dctB (or dcuS) for the utilization of C 4 dicarboxylate (15,16), as well as the ABC-type transport system PtsSABC and sensor kinase PhoR for the specific uptake of inorganic phosphate (55).…”

Section: Discussionmentioning

confidence: 99%

“…However, from a physiological perspective, proteins with a dual role of nutrient sensing and uptake could have evolved, and moreover, nutrient uptake can potentially act as the stimulus that activates a given kinase (19)(20)(21). The E. coli UhpC transceptor is the only such example of a transporter-like kinase so far found in bacteria (20,54). UhpC is capable of transporting and sensing glucose-6-phosphate (56).…”

Section: Discussionmentioning

confidence: 99%

“…CbrA works together with its cognate RR CbrB, which possesses a 54 -interacting output domain. Both CbrA and CbrB are essential for the activation of genes involved in nutrient acquisition, including hut genes for the utilization of histidine and urocanate (urocanate is the first intermediate of the histidine degradation pathway) (26,27).…”

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Role of the Transporter-Like Sensor Kinase CbrA in Histidine Uptake and Signal Transduction

et al. 2015

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CbrA is an atypical sensor kinase found in Pseudomonas. The autokinase domain is connected to a putative transporter of the sodium/solute symporter family (SSSF). CbrA functions together with its cognate response regulator, CbrB, and plays an important role in nutrient acquisition, including regulation of hut genes for the utilization of histidine and its derivative, urocanate. Here we report on the findings of a genetic and biochemical analysis of CbrA with a focus on the function of the putative transporter domain. The work was initiated with mutagenesis of histidine uptake-proficient strains to identify histidine-specific transport genes located outside the hut operon. Genes encoding transporters were not identified, but mutations were repeatedly found in cbrA. This, coupled with the findings of [ 3 H]histidine transport assays and further mutagenesis, implicated CbrA in histidine uptake. In addition, mutations in different regions of the SSSF domain abolished signal transduction. Site-specific mutations were made at four conserved residues: W55 and G172 (SSSF domain), H766 (H box), and N876 (N box). The mutations W55G, G172H, and N876G compromised histidine transport but had minimal effects on signal transduction. The H766G mutation abolished both transport and signal transduction, but the capacity to transport histidine was restored upon complementation with a transport-defective allele of CbrA, most likely due to interdomain interactions. Our combined data implicate the SSSF domain of CbrA in histidine transport and suggest that transport is coupled to signal transduction. IMPORTANCENutrient acquisition in bacteria typically involves membrane-bound sensors that, via cognate response regulators, determine the activity of specific transporters. However, nutrient perception and uptake are often coupled processes. Thus, from a physiological perspective, it would make sense for systems that couple the process of signaling and transport within a single protein and where transport is itself the stimulus that precipitates signal transduction to have evolved. The CbrA regulator in Pseudomonas represents a unique type of sensor kinase whose autokinase domain is connected to a transporter domain. We present genetic and biochemical evidence that suggests that CbrA plays a dual role in histidine uptake and sensing and that transport is dependent on signal transduction.T he ability to recognize and convert external environmental stimuli into appropriate physiological responses is of fundamental importance for all organisms. In bacteria, signal transduction is predominantly mediated by two-component regulatory systems (TCSs) consisting of a sensor kinase (SK) and a cognate response regulator (RR) (1, 2). Both proteins are typically composed of two distinct functional domains (3): a variable N-terminal signal input domain and a conserved C-terminal autokinase domain for the SK and a conserved N-terminal receiver (Rec) domain and a variable C-terminal output domain for the RR. Signal transduction is achieved via ph...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Role of the Transporter-Like Sensor Kinase CbrA in Histidine Uptake and Signal Transduction

et al. 2015

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“…However, the wild-type strain has Crp and can make cyclic AMP, and can therefore grow on glycerol. It cannot grow in the presence of a nonmetabolizable glucose analogue such as 2-deoxyglucose (2DG) or α-methylglucoside (αMG) which inhibits glycerol kinase and adenylate cyclase activities (33, 34). The mutational event involving IS5 activation of glpFK expression, described below, allows the cell to overcome the inhibitory effect of a non-metabolizable sugar analogue, enabling glycerol utilization in its presence (35).…”

Section: Introductionmentioning

confidence: 99%

Transposon-mediated directed mutation in bacteria and eukaryotes

2017

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Transposon-mediated “directed” mutations occur at higher frequencies when beneficial than when detrimental and relieve the stress that causes them. The first and best-studied example involves regulation of Insertion Sequence-5 (IS5) insertion into a specific activating site upstream of the glycerol utilization operon in Escherichia coli, glpFK. This event promotes high level expression of the glpFK operon, allowing glycerol utilization in wild type cells under inhibitory conditions. The phosphoenolpyruvate-dependent, sugar transporting, phosphotransferase system (PTS) influences this process by regulating cytoplasmic glycerol-3-phosphate and cyclic AMP concentrations. Insertion frequencies are determined by IS5-specific tetranucleotide target sequences in stress-induced (DNA) duplex destabilization (SIDD) structures counteracted by two DNA binding proteins, GlpR and Crp which directly inhibit insertion, responding to cytoplasmic glycerol-3-phosphate and cyclic AMP, respectively. Expression of the E. coli master regulator of flagellar gene control, flhDC, is subject to activation by IS elements by a directed mechanism, and zinc-induced transposon-mediated zinc resistance has been demonstrated in Cupriavidus metallidurans. The use of DNA conformation and DNA binding proteins to control transposon hopping also occurs in eukaryotes.

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“…In eukaryotes, the enzymes that perform glucose phosphorylation are usually hexokinases [28]. Most prokaryotes use the phosphoenolpyruvate-dependent phosphotransferase system (PTS) which couples carbohydrate transport to its concomitant phosphorylation [72]. However, even when bacteria predominantly use PTS, they also possess active Glks [64,56,27,35]).…”

Section: Introductionmentioning

confidence: 99%