Incoherent Feedforward Control Governs Adaptation of Activated Ras in a Eukaryotic Chemotaxis Pathway

Overview

Journal Sci Signal

Specialties Cell Biology
Physiology
Science

Date 2012 Jan 5

PMID 22215733

Citations 91

Authors

Kosuke Takeda

Danying Shao

Micha Adler

Pascale G Charest

William F Loomis

Herbert Levine

Alex Groisman

Wouter-Jan Rappel

Richard A Firtel

Affiliations

Soon will be listed here.

Abstract

Adaptation in signaling systems, during which the output returns to a fixed baseline after a change in the input, often involves negative feedback loops and plays a crucial role in eukaryotic chemotaxis. We determined the dynamical response to a uniform change in chemoattractant concentration of a eukaryotic chemotaxis pathway immediately downstream from G protein-coupled receptors. The response of an activated Ras showed near-perfect adaptation, leading us to attempt to fit the results using mathematical models for the two possible simple network topologies that can provide perfect adaptation. Only the incoherent feedforward network accurately described the experimental results. This analysis revealed that adaptation in this Ras pathway is achieved through the proportional activation of upstream components and not through negative feedback loops. Furthermore, these results are consistent with a local excitation, global inhibition mechanism for gradient sensing, possibly with a Ras guanosine triphosphatase-activating protein acting as a global inhibitor.

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