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G-Protein-Coupled Enzyme Cascades Have Intrinsic Properties that Improve Signal Localization and Fidelity

Sharad Ramanathan ^*, Peter B. Detwiler , Anirvan M. Sengupta  and Boris I. Shraiman 

^* Bell Labs, Lucent Technologies, Murray Hill, New Jersey; Dept of Physiology and Biophysics, University of Washington, Seattle, Washington; and Department of Physics and the BioMaPS Institute, Rutgers University, Piscataway, New Jersey

Correspondence: Address reprint requests to Boris I. Shraiman at his current address, Kavli Institute for Theoretical Physics, University of California, Santa Barbara, CA. 93016. Tel.: 805-893-2835; E-mail: shraiman{at}kitp.ucsb.edu.

G-protein-coupled enzyme cascades are used by eukaryotic cells to detect external signals and transduce them into intracellular messages that contain biological information relevant to the cell's function. Since G-protein-coupled receptors that are designed to detect different kinds of external signals can generate the same kind of intracellular response, effective signaling requires that there are mechanisms to increase signal specificity and fidelity. Here we examine the kinetic equations for the initial three stages in a generic G-protein-coupled cascade and show that the physical properties of the transduction pathway result in two intrinsic features that benefit signaling. 1), The response to a single activated receptor is naturally confined to a localized spatial domain, which could improve signal specificity by reducing cross talk. 2), The peak of the response generated by such a signaling domain is limited. This saturation effect reduces trial-to-trial variability and increases signaling fidelity by limiting the response to receptors that remain active for longer than average. We suggest that this mechanism for reducing response fluctuations may be a contributing factor in making the single photon responses of vertebrate retinal rods so remarkably reproducible.

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