Enzyme localization can drastically affect signal amplification in signal transduction pathways

TL;DR

This paper explores how the spatial localization of enzymes in push-pull signal transduction networks significantly influences signal amplification and response sharpness, with implications for cellular signaling efficiency.

Contribution

It demonstrates that enzyme localization impacts gain and response sharpness, revealing new insights into spatial regulation of signal transduction pathways.

Findings

Enzyme colocalization maximizes signal gain.

Spatial separation reduces response sharpness.

Diffusion constants influence the effect of enzyme localization.

Abstract

Push-pull networks are ubiquitous in signal transduction pathways in both prokaryotic and eukaryotic cells. They allow cells to strongly amplify signals via the mechanism of zero-order ultrasensitivity. In a push-pull network, two antagonistic enzymes control the activity of a protein by covalent modification. These enzymes are often uniformly distributed in the cytoplasm. They can, however, also be colocalized in space, for instance, near the pole of the cell. Moreover, it is increasingly recognized that these enzymes can also be spatially separated, leading to gradients of the active form of the messenger protein. Here, we investigate the consequences of the spatial distributions of the enzymes for the amplification properties of push-pull networks. Our calculations reveal that enzyme localization by itself can have a dramatic effect on the gain. The gain is maximized when the two enzymes are either uniformly distributed or colocalized in one region in the cell. Depending on the diffusion constants, however, the sharpness of the response can be strongly reduced when the enzymes are spatially separated. We discuss how our predictions could be tested experimentally.