A human transporter protein that mediates the final excretion step for toxic organic cations.

IF 11.3 1区化学 Q1 CHEMISTRY, PHYSICAL

ACS Catalysis Pub Date : 2005-12-13 Epub Date: 2005-12-05 DOI:10.1073/pnas.0506483102

Masato Otsuka, Takuya Matsumoto, Riyo Morimoto, Shigeo Arioka, Hiroshi Omote, Yoshinori Moriyama

引用次数: 552

Abstract

In mammals, toxic electrolytes of endogenous and exogenous origin are excreted through the urine and bile. Before excretion, these compounds cross numerous cellular membranes in a transporter-mediated manner. However, the protein transporters involved in the final excretion step are poorly understood. Here, we show that MATE1, a human and mouse orthologue of the multidrug and toxin extrusion family conferring multidrug resistance on bacteria, is primarily expressed in the kidney and liver, where it is localized to the luminal membranes of the urinary tubules and bile canaliculi. When expressed in HEK293 cells, MATE1 mediates H(+)-coupled electroneutral exchange of tetraethylammonium and 1-methyl-4-phenylpyridinium. Its substrate specificity is similar to those of renal and hepatic H(+)-coupled organic cations (OCs) export. Thus, MATE1 appears to be the long searched for polyspecific OC exporter that directly transports toxic OCs into urine and bile.

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一种人体转运蛋白，介导有毒有机阳离子的最后排泄步骤。

在哺乳动物中，内源性和外源性的有毒电解质通过尿液和胆汁排出。在排泄之前，这些化合物以转运体介导的方式穿过许多细胞膜。然而，参与最后排泄步骤的蛋白质转运蛋白却知之甚少。在这里，我们发现MATE1是人类和小鼠的多药和毒素挤出家族同源物，赋予细菌多药耐药性，主要在肾脏和肝脏中表达，定位于尿小管和胆管的管腔膜。当在HEK293细胞中表达时，MATE1介导H(+)偶联的四乙基铵和1-甲基-4-苯基吡啶的电中性交换。其底物特异性与肾脏和肝脏的H(+)偶联有机阳离子(OCs)出口相似。因此，MATE1似乎是长期寻找的多特异性OC出口者，它直接将有毒OC运输到尿液和胆汁中。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Catalysis CHEMISTRY, PHYSICAL-

CiteScore

20.80

自引率

6.20%

发文量

1253

审稿时长

1.5 months

期刊介绍： ACS Catalysis is an esteemed journal that publishes original research in the fields of heterogeneous catalysis, molecular catalysis, and biocatalysis. It offers broad coverage across diverse areas such as life sciences, organometallics and synthesis, photochemistry and electrochemistry, drug discovery and synthesis, materials science, environmental protection, polymer discovery and synthesis, and energy and fuels. The scope of the journal is to showcase innovative work in various aspects of catalysis. This includes new reactions and novel synthetic approaches utilizing known catalysts, the discovery or modification of new catalysts, elucidation of catalytic mechanisms through cutting-edge investigations, practical enhancements of existing processes, as well as conceptual advances in the field. Contributions to ACS Catalysis can encompass both experimental and theoretical research focused on catalytic molecules, macromolecules, and materials that exhibit catalytic turnover.