A human transporter protein that mediates the final excretion step for toxic organic cations.
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.
Otsuka
Masato
M
Advanced Science Research Center, Okayama University, Dentistry and Pharmaceutical Sciences, Japan.
Matsumoto
Takuya
T
Morimoto
Riyo
R
Arioka
Shigeo
S
Omote
Hiroshi
H
Moriyama
Yoshinori
Y
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
D002412:Cations; D017931:DNA Primers; D018076:DNA, Complementary; D027701:Organic Cation Transport Proteins; D019789:Tetraethylammonium; D015655:1-Methyl-4-phenylpyridinium