Multiple nutrient transporters enable cells to mitigate a rate-affinity tradeoff.
Multiple nutrient transporters enable cells to mitigate a rate-affinity tradeoff.
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多种营养转运蛋白使细胞能够减轻速率亲和力的权衡。
DOI：
10.1371/journal.pcbi.1010060
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发表时间：
2022-04
影响因子：
4.3
通讯作者：
中科院分区：
文献类型：
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作者：
真核生物基因组通常编码同一营养物质的多种转运蛋白。例如，芽殖酵母有17种己糖转运蛋白（HXT），所有这些转运蛋白都可能转运葡萄糖。使用数学建模，我们表明，转运使用促进扩散或共输可以有一个率亲和力的权衡，在最大运输速率的增加降低转运的表观亲和力。这些变化非单调地影响输入通量，并且对于给定浓度的细胞外营养物，存在一种以其亲和力为特征的转运蛋白，其具有比任何其他转运蛋白更高的输入通量。通过编码多种转运蛋白，细胞可以通过在较低浓度的营养物质中表达具有较高亲和力的转运蛋白来减轻权衡。我们验证了我们的预测，使用荧光标记的7个HXT基因在芽殖酵母，并按照他们的表达随着时间的推移，在分批培养。使用已知的亲和力相应的转运蛋白，我们表明，他们在葡萄糖的调节是广泛一致的速率亲和力权衡：作为葡萄糖福尔斯下降，不同的转运蛋白的水平峰值的顺序，主要是遵循他们的亲和力葡萄糖。更一般地说，进化受到权衡的限制。我们的研究结果表明，一个这样的权衡往往发生在营养物质的细胞运输。从酵母到人类，细胞通常表达多种不同类型的转运蛋白，用于相同的营养素，令人困惑的是，为什么没有表达单一的高亲和力转运蛋白。在这里，我们最初使用数学模型来证明，运输促进扩散和那些由质子动力都可以表现出一个率亲和性权衡，相当一般的条件。具有较高亲和力的转运蛋白必然具有较低的速率，反之亦然。权衡意味着，有一个范围内的营养浓度的转运蛋白，其特点是其亲和力，具有较高的进口流量比任何其他转运蛋白具有不同的亲和力。为了减轻这种权衡，基因组可能因此编码多种不同的转运蛋白，并且以最佳输入浓度表达每种转运蛋白的细胞将以更高的速率吸收营养。一致地，我们表明，作为细胞的芽殖酵母消耗葡萄糖，他们表达五种类型的己糖转运蛋白的顺序如下的转运蛋白的亲和力。
Eukaryotic genomes often encode multiple transporters for the same nutrient. For example, budding yeast has 17 hexose transporters (HXTs), all of which potentially transport glucose. Using mathematical modelling, we show that transporters that use either facilitated diffusion or symport can have a rate-affinity tradeoff, where an increase in the maximal rate of transport decreases the transporter’s apparent affinity. These changes affect the import flux non-monotonically, and for a given concentration of extracellular nutrient there is one transporter, characterised by its affinity, that has a higher import flux than any other. Through encoding multiple transporters, cells can therefore mitigate the tradeoff by expressing those transporters with higher affinities in lower concentrations of nutrients. We verify our predictions using fluorescent tagging of seven HXT genes in budding yeast and follow their expression over time in batch culture. Using the known affinities of the corresponding transporters, we show that their regulation in glucose is broadly consistent with a rate-affinity tradeoff: as glucose falls, the levels of the different transporters peak in an order that mostly follows their affinity for glucose. More generally, evolution is constrained by tradeoffs. Our findings indicate that one such tradeoff often occurs in the cellular transport of nutrients. From yeast to humans, cells often express multiple different types of transporters for the same nutrient, and it is puzzling why a single high-affinity transporter is not expressed instead. Here we initially use mathematical modelling to demonstrate that transporters facilitating diffusion and those powered by the proton motive force can both exhibit a rate-affinity tradeoff, for quite general conditions. A transporter with a higher affinity necessarily has a lower rate, and vice versa. The tradeoff implies that there is a range of nutrient concentrations for which a transporter, characterised by its affinity, has a higher import flux than any other transporter with a different affinity. To mitigate the tradeoff, genomes may therefore encode multiple different transporters, and cells that express each transporter in the concentrations where it imports best will uptake nutrients at higher rates. Consistently, we show that as cells of budding yeast consume glucose, they express five types of hexose transporters in an order that follows the transporters’ affinities.
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DOI：
10.1093/database/baz022
发表时间：
2019-03-20
影响因子：
5.8
作者：
Correia, Kevin;Yu, Shi M.;Mahadevan, Radhakrishnan
通讯作者：
Mahadevan, Radhakrishnan
影响因子：
2.1
作者：
Gudelj, I.;Beardmore, R. E.;Maclean, R. C.
通讯作者：
Maclean, R. C.
影响因子：
2.6
作者：
Diderich, JA;Schuurmans, JM;Van Dam, K
通讯作者：
Van Dam, K
影响因子：
10.7
作者：
Nguyen LT;Schmidt HA;von Haeseler A;Minh BQ
通讯作者：
Minh BQ
影响因子：
10.7
作者：
Katoh K;Standley DM
通讯作者：
Standley DM