Modeling Regulation of Zinc Uptake via ZIP Transporters in Yeast and Plant Roots

TL;DR

This study develops and analyzes mathematical models of zinc uptake regulation in yeast and plant roots, revealing mechanisms of transporter regulation and stability of zinc homeostasis.

Contribution

It introduces a general ODE-based modeling framework for zinc regulation, adapting it to yeast and plant systems, and compares different regulatory models for plant ZIP transporters.

Findings

Yeast model confirms different affinities of ZRT1 and ZRT2.

Positive feedback in ZAP1 stabilizes high influx rates.

Activator/inhibitor model best maintains zinc homeostasis in plants.

Abstract

In yeast (Saccharomyces cerevisiae) and plant roots (Arabidopsis thaliana) zinc enters the cells via influx transporters of the ZIP family. Since zinc is both essential for cell function and toxic at high concentrations, tight regulation is essential for cell viability. We provide new insight into the underlying mechanisms, starting from a general model based on ordinary differential equations and adapting it to the specific cases of yeast and plant root cells. In yeast, zinc is transported by the transporters ZRT1 and ZRT2, which are both regulated by the zinc-responsive transcription factor ZAP1. Using biological data, parameters were estimated and analyzed, confirming the different affinities of ZRT1 and ZRT2 reported in the literature. Furthermore, our model suggests that the positive feedback in ZAP1 production has a stabilizing function at high influx rates. In plant roots, various ZIP transporters are involved in zinc uptake. Their regulation is largely unknown, but bZIP transcription factors are thought to be involved. We set up three putative models: activator only, activator with dimerization and activator/inhibitor. These were fitted to measurements and analyzed. Simulations show that the activator/inhibitor model outperforms the other two in providing robust and stable homeostasis at reasonable parameter ranges.