title: A modular gradient-sensing network for chemotaxis in Escherichia coli revealed by responses to time-varying stimuli.
abstract: The Escherichia coli chemotaxis-signaling pathway computes time derivatives of chemoeffector concentrations. This network features modules for signal reception/amplification and robust adaptation, with sensing of chemoeffector gradients determined by the way in which these modules are coupled in vivo. We characterized these modules and their coupling by using fluorescence resonance energy transfer to measure intracellular responses to time-varying stimuli. Receptor sensitivity was characterized by step stimuli, the gradient sensitivity by exponential ramp stimuli, and the frequency response by exponential sine-wave stimuli. Analysis of these data revealed the structure of the feedback transfer function linking the amplification and adaptation modules. Feedback near steady state was found to be weak, consistent with strong fluctuations and slow recovery from small perturbations. Gradient sensitivity and frequency response both depended strongly on temperature. We found that time derivatives can be computed by the chemotaxis system for input frequencies below 0.006 Hz at 22 degrees C and below 0.018 Hz at 32 degrees C. Our results show how dynamic input-output measurements, time honored in physiology, can serve as powerful tools in deciphering cell-signaling mechanisms.
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Shimizu
authors.forename: Yuhai
authors.initials: Y
authors.lastname: Tu
authors.forename: Howard C
authors.initials: HC
authors.lastname: Berg
mesh_terms: D002138:Calibration; D002633:Chemotaxis; D004926:Escherichia coli / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D025461:Feedback, Physiological; D031541:Fluorescence Resonance Energy Transfer; D011494:Protein Kinases / Q000378:metabolism; D053038:Quorum Sensing; D011956:Receptors, Cell Surface / Q000378:metabolism; D013696:Temperature; D013997:Time Factors
chemical_list: D011956:Receptors, Cell Surface; D011494:Protein Kinases