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

机译:通过ZIP转运蛋白在酵母和植物根系中吸收锌的模拟调控

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摘要

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.
机译:在酵母(Saccharomyces cerevisiae)和植物根(Arabidopsis thaliana)中,锌通过ZIP家族的转运蛋白进入细胞。由于锌对于细胞功能和高浓度毒性都是必不可少的,因此严格调节对于细胞活力至关重要。我们提供了对潜在机制的新见解,从基于普通微分方程的通用模型开始,并将其适应于酵母和植物根细胞的特定情况。在酵母中,锌由转运蛋白ZRT1和ZRT2转运,这两个转运蛋白均受锌响应转录因子ZAP1的调节。使用生物学数据,对参数进行了估计和分析,确认了文献中报道的ZRT1和ZRT2的不同亲和力。此外,我们的模型表明ZAP1生产中的正反馈在高流入率下具有稳定功能。在植物根部,各种ZIP转运蛋白在锌吸收中发挥作用。它们的调节在很大程度上是未知的,但是认为涉及bZIP转录因子。我们基于以下三个推定模型:仅激活剂,具有二聚化的激活剂和激活剂-抑制剂对。这些适合测量和分析。仿真结果表明,在合理的参数范围内,激活剂-抑制剂模型在提供强大而稳定的动态平衡方面优于其他两个模型。

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