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

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 play a role in zinc uptake. Their regulation is largely unknown, but bZIP transcription factors are thought to be involved. We set up three putative models based on: an activator only, an activator with dimerization and an activator-inhibitor pair. 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.

Heavy Metal Uptake and Transport in Plants

“…Up to now over 25 ZIP family transporters have been identified. On the basis of amino acid similarities, the respective genes fall into two subfamilies (Grotz et al 1998;Claus and Chavarría-Krauser 2012). The ZIP families of transporters are involved in the translocation of divalent cations across cellular membranes, and they are found in many plants, bacteria, fungi, and animal species.…”

“…They were discovered on the basis of their similarity with IRT1 which is 54-65 %. Studies have demonstrated that normally yeast has two systems of Zn uptake (Claus and Chavarría-Krauser 2012). One system has high affinity and is activated only in Zn deficit cells, and the other has low affinity and is induced in cells with enough zinc.…”

Global Hopf bifurcation in the ZIP regulatory system

“…In Claus and Chavarría-Krauser (2012) we studied mathematical models for the regulation of ZIP transporters in response to external zinc concentration. The most promising model identified in this study included a dimerizing activator A, as well as an inhibitor I that senses the internal zinc concentration Z and inhibits the activator.…”

“…The parameter κ describes the induction of gene activity (u 1 ) by the dimerized activator (u 3 ), γ 1 and γ 3 the binding between activator and inhibitor (u 3 and u 4 ), γ 2 the binding between zinc (u 2 ) and the inhibitor (u 4 ), and K is the Michaelis constant of the reaction between external zinc (µ) and zinc transporters (u 1 ). All parameter values, here K = 13, κ = 20, γ 1 = 380, γ 2 = 1000, γ 3 = 1672, have been estimated from literature and by fitting the model to experimental data (Claus and Chavarría-Krauser, 2012). As a property of the soil, the external zinc concentration is considered as the bifurcation parameter µ ∈ M.…”

Nutrition Research and the Impact of Computational Systems Biology

“…A deterministic algorithm integrates the ODEs to produce a nonrandom solution [49]. The modelling of nutrient-centred biochemical pathways with the ODE approach has been extremely useful to the field of nutrition [50][51][52][53][54][55][56][57]. For instance, the folate cycle is a pertinent example of how nutrition has benefited from ODE systems modelling.…”