Pleiotropy enables specific and accurate signaling in the presence of ligand cross talk

TL;DR

This paper demonstrates that receptor pleiotropy enables cells to accurately distinguish and sense multiple ligands despite high cross talk, by modeling how a single receptor can produce multiple outputs for precise environmental sensing.

Contribution

The study introduces a minimal model showing how receptor pleiotropy can resolve the cross talk problem, enhancing signaling specificity and accuracy in complex receptor-ligand networks.

Findings

A single pleiotropic receptor can identify multiple ligands simultaneously.

Fundamental limits of signaling specificity and accuracy are characterized.

Pleiotropy serves as a solution to cross talk in cellular signaling.

Abstract

Living cells sense their environment through the binding of extra-cellular molecular ligands to cell surface receptors. Puzzlingly, vast numbers of signaling pathways exhibit a high degree of cross talk between different signals whereby different ligands act through the same receptor or shared components downstream. It remains unclear how a cell can accurately process information from the environment in such cross-wired pathways. We show that a feature which commonly accompanies cross talk - signaling pleiotropy (the ability of a receptor to produce multiple outputs) - offers a solution to the cross talk problem. In a minimal model we show that a single pleiotropic receptor can simultaneously identify and accurately sense the concentrations of arbitrary unknown ligands present individually or in a mixture. We calculate the fundamental limits of the signaling specificity and accuracy of such signaling schemes. The model serves as an elementary "building block" towards understanding more complex cross-wired receptor-ligand signaling networks.