TY - JOUR
T1 - A human transporter protein that mediates the final excretion step for toxic organic cations
AU - Otsuka, Masato
AU - Matsumoto, Takuya
AU - Morimoto, Riyo
AU - Arioka, Shigeo
AU - Omote, Hiroshi
AU - Moriyama, Yoshinori
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/12/13
Y1 - 2005/12/13
N2 - 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.
AB - 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.
KW - Bile canaliculi
KW - Multidrug and toxin extrusion
KW - Multidrug export
KW - Urinary tubule
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U2 - 10.1073/pnas.0506483102
DO - 10.1073/pnas.0506483102
M3 - Article
C2 - 16330770
AN - SCOPUS:29144523534
VL - 102
SP - 17923
EP - 17928
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 50
ER -