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

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

Research output: Contribution to journalArticle

392 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)17923-17928
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number50
DOIs
Publication statusPublished - Dec 13 2005

Fingerprint

Poisons
Cations
Bile
Bile Canaliculi
Urine
1-Methyl-4-phenylpyridinium
Kidney
Proteins
Tetraethylammonium
Membranes
HEK293 Cells
Liver
Multiple Drug Resistance
Substrate Specificity
Electrolytes
Mammals
Bacteria

Keywords

  • Bile canaliculi
  • Multidrug and toxin extrusion
  • Multidrug export
  • Urinary tubule

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

A human transporter protein that mediates the final excretion step for toxic organic cations. / Otsuka, Masato; Matsumoto, Takuya; Morimoto, Riyo; Arioka, Shigeo; Omote, Hiroshi; Moriyama, Yoshinori.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 50, 13.12.2005, p. 17923-17928.

Research output: Contribution to journalArticle

Otsuka, Masato ; Matsumoto, Takuya ; Morimoto, Riyo ; Arioka, Shigeo ; Omote, Hiroshi ; Moriyama, Yoshinori. / A human transporter protein that mediates the final excretion step for toxic organic cations. In: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Vol. 102, No. 50. pp. 17923-17928.
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