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 (MATE) 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 (TEA) and 1-methyl-4-phenylpyridinium (MPP). 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.
en-copyright= kn-copyright= en-aut-name=OtsukaMasato en-aut-sei=Otsuka en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoTakuya en-aut-sei=Matsumoto en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MorimotoRiyo en-aut-sei=Morimoto en-aut-mei=Riyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AriokaShigeo en-aut-sei=Arioka en-aut-mei=Shigeo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OmoteHiroshi en-aut-sei=Omote en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoriyamaYoshinori en-aut-sei=Moriyama en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University affil-num=4 en-affil= kn-affil=Okayama University affil-num=5 en-affil= kn-affil=Okayama University affil-num=6 en-affil= kn-affil=Okayama University en-keyword=MATE kn-keyword=MATE en-keyword=multidrug export kn-keyword=multidrug export en-keyword=excretion kn-keyword=excretion en-keyword=toxin kn-keyword=toxin en-keyword=urinary tubule kn-keyword=urinary tubule en-keyword=bile canaliculus kn-keyword=bile canaliculus en-keyword=organic cation kn-keyword=organic cation en-keyword=H+/cation antiport. kn-keyword=H+/cation antiport. END start-ver=1.4 cd-journal=joma no-vol=105 cd-vols= no-issue=15 article-no= start-page=5683 end-page=5686 dt-received= dt-revised= dt-accepted= dt-pub-year=2008 dt-pub=20080401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Identification of a vesicular nucleotide transporter en-subtitle= kn-subtitle= en-abstract= kn-abstract=ATP is a major chemical transmitter in purinergic signal transmission. Before secretion, ATP is stored in secretory vesicles found in purinergic cells. Although the presence of active transport mechanisms for ATP has been postulated for a long time, the proteins responsible for its vesicular accumulation remains unknown. The transporter encoded by the human and mouse SLC17A9 gene, a novel member of an anion transporter family, was predominantly expressed in the brain and adrenal gland. The mouse and bovine counterparts were associated with adrenal chromaffin granules. Proteoliposomes containing purified transporter actively took up ATP, ADP, and GTP by using membrane potential as the driving force. The uptake properties of the reconstituted transporter were similar to that of the ATP uptake by synaptic vesicles and chromaffin granules. Suppression of endogenous SLC17A9 expression in PC12 cells decreased exocytosis of ATP. These findings strongly suggest that SLC17A9 protein is a vesicular nucleotide transporter and should lead to the elucidation of the molecular mechanism of ATP secretion in purinergic signal transmission.
en-copyright= kn-copyright= en-aut-name=SawadaKeisuke en-aut-sei=Sawada en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EchigoNoriko en-aut-sei=Echigo en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=JugeNarinobu en-aut-sei=Juge en-aut-mei=Narinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyajiTakaaki en-aut-sei=Miyaji en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OtsukaMasato en-aut-sei=Otsuka en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OmoteHiroshi en-aut-sei=Omote en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamamotoAkitsugu en-aut-sei=Yamamoto en-aut-mei=Akitsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MoriyamaYoshinori en-aut-sei=Moriyama en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University affil-num=4 en-affil= kn-affil=Okayama University affil-num=5 en-affil= kn-affil=Okayama University affil-num=6 en-affil= kn-affil=Okayama University affil-num=7 en-affil= kn-affil=Nagahama Institute of Technology affil-num=8 en-affil= kn-affil=Okayama University en-keyword=chromaffin granule kn-keyword=chromaffin granule en-keyword=synaptic vesicle kn-keyword=synaptic vesicle en-keyword=ATP kn-keyword=ATP en-keyword=storage and exocytosis kn-keyword=storage and exocytosis en-keyword=purinergic signaling. kn-keyword=purinergic signaling. END