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

Phys Rev E. 2021 Apr;103(4-1):042401. doi: 10.1103/PhysRevE.103.042401.

Abstract

Living cells sense their environment through the binding of extracellular 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" toward understanding more complex cross-wired receptor-ligand signaling networks.