title: A human transporter protein that mediates the final excretion step for toxic organic cations.
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.
authors.affiliation: Advanced Science Research Center, Okayama University, Dentistry and Pharmaceutical Sciences, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Otsuka
authors.forename: Takuya
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Riyo
authors.initials: R
authors.lastname: Morimoto
authors.forename: Shigeo
authors.initials: S
authors.lastname: Arioka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Omote
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Moriyama
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000378:metabolism; D000595:Amino Acid Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D002412:Cations / Q000378:metabolism*; D002460:Cell Line; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D016296:Mutagenesis; D027701:Organic Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism; D017433:Protein Structure, Secondary; D013379:Substrate Specificity; D019789:Tetraethylammonium / Q000378:metabolism
chemical_list: D002412:Cations; D017931:DNA Primers; D018076:DNA, Complementary; D027701:Organic Cation Transport Proteins; D019789:Tetraethylammonium; D015655:1-Methyl-4-phenylpyridinium