Push-Pull and Feedback Mechanisms Can Align Signaling System Outputs with Inputs

doi:10.1016/j.cels.2016.10.002

Push-Pull and Feedback Mechanisms Can Align Signaling System Outputs with Inputs

2016-11-01

22

OA

AI

Alejandro Colman‐Lerner

R

Roger Brent *

DOI：10.1016/j.cels.2016.10.002

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Abstract

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Many cell signaling systems, including the yeast pheromone response system, exhibit ``dose-response alignment'' (DoRA), in which output of one or more downstream steps closely matches the fraction of occupied receptors. DoRA can improve the fidelity of transmitted dose information. Here, we searched systematically for biochemical network topologies that produced DoRA. Most networks, including many containing feedback and feedforward loops, could not produce DoRA. However, networks including `` push-pull'' mechanisms, in which the active form of a signaling species stimulates downstream activity and the nominally inactive form reduces downstream activity, enabled perfect DoRA. Networks containing feedbacks enabled DoRA, but only if they also compared feedback to input and adjusted output to match. Our results establish push-pull as a non-feedback mechanism to align output with variable input and maximize information transfer in signaling systems. They also suggest genetic approaches to determine whether particular signaling systems use feedback or push-pull control.

Keywords:

INTERCONVERTIBLE ENZYME CASCADES

YEAST SACCHAROMYCES-CEREVISIAE

ALPHA-FACTOR RECEPTOR

LEXA GENE-PRODUCT

COVALENT MODIFICATION

QUANTITATIVE-ANALYSIS

METABOLIC-REGULATION

PERFECT ADAPTATION

PHEROMONE RESPONSE

NETWORK MOTIFS

Push-Pull and Feedback Mechanisms Can Align Signaling System Outputs with Inputs

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