Laboratory for Molecular Ecotoxicology, Division for Marine and Environmental Research, Ruđer Bošković Institute, Zagreb, Croatia.
Oxford Institute for Radiation Oncology, University of Oxford, Oxford, England, United Kingdom.
Sci Rep. 2016 Jun 30;6:28937. doi: 10.1038/srep28937.
Multidrug and toxin extrusion (MATE) proteins are involved in the extrusion of endogenous compounds and xenobiotics across the plasma membrane. They are conserved from bacteria to mammals, with different numbers of genes within groups. Here, we present the first data on identification and functional characterization of Mate proteins in zebrafish (Danio rerio). Phylogenetic analysis revealed six Mates in teleost fish, annotated as Mate3-8, which form a distinct cluster separated from the tetrapod MATEs/Mates. Synteny analysis showed that zebrafish mate genes are orthologous to human MATEs. Gene expression analysis revealed that all the mate transcripts were constitutively and differentially expressed during embryonic development, followed by pronounced and tissue-specific expression in adults. Functional analyses were performed using transport activity assays with model substrates after heterologous overexpression of five zebrafish Mates in HEK293T cells. The results showed that zebrafish Mates interact with both physiological and xenobiotic substances but also substantially differ with respect to the interacting compounds and interaction strength in comparison to mammalian MATEs/Mates. Taken together, our data clearly indicate a potentially important role for zebrafish Mate transporters in zebrafish embryos and adults and provide a basis for detailed functional characterizations of single zebrafish Mate transporters.
多药和毒素外排（MATE）蛋白参与内源性化合物和外源性毒物穿过质膜的外排。它们在从细菌到哺乳动物的范围内是保守的，在不同的群体中有不同数量的基因。在这里，我们首次提供了斑马鱼（Danio rerio）中 Mate 蛋白的鉴定和功能特征的相关数据。系统发育分析显示，硬骨鱼类有六种 Mate，被注释为 Mate3-8，它们形成了一个与四足动物 MATEs/Mates 分离的独特簇。基因表达分析显示，所有的 mate 转录本在胚胎发育过程中持续且差异表达，随后在成年期表现出显著的组织特异性表达。功能分析是通过在 HEK293T 细胞中异源过表达五种斑马鱼 Mate 后，利用模型底物的转运活性测定来进行的。结果表明，斑马鱼 Mate 与生理和外源性物质相互作用，但与哺乳动物 MATEs/Mates 相比，在相互作用的化合物和相互作用强度方面也有很大的不同。综上所述，我们的数据清楚地表明，斑马鱼 Mate 转运蛋白在斑马鱼胚胎和成年期可能具有重要作用，并为详细的单个斑马鱼 Mate 转运蛋白功能特征提供了基础。
