Functional complementation between a novel mammalian polygenic transport complex and an evolutionarily ancient organic solute transporter, OSTalpha-OSTbeta.
Article Details
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Seward DJ, Koh AS, Boyer JL, Ballatori N
Functional complementation between a novel mammalian polygenic transport complex and an evolutionarily ancient organic solute transporter, OSTalpha-OSTbeta.
J Biol Chem. 2003 Jul 25;278(30):27473-82. Epub 2003 Apr 28.
- PubMed ID
- 12719432 [ View in PubMed]
- Abstract
These studies identify an organic solute transporter (OST) that is generated when two novel gene products are co-expressed, namely human OSTalpha and OSTbeta or mouse OSTalpha and OSTbeta. The results also demonstrate that the mammalian proteins are functionally complemented by evolutionarily divergent Ostalpha-Ostbeta proteins recently identified in the little skate, Raja erinacea, even though the latter exhibit only 25-41% predicted amino acid identity with the mammalian proteins. Human, mouse, and skate OSTalpha proteins are predicted to contain seven transmembrane helices, whereas the OSTbeta sequences are predicted to have a single transmembrane helix. Human OSTalpha-OSTbeta and mouse Ostalpha-Ostbeta cDNAs were cloned from liver mRNA, sequenced, expressed in Xenopus laevis oocytes, and tested for their ability to functionally complement the corresponding skate proteins by measuring transport of [3H]estrone 3-sulfate. None of the proteins elicited a transport signal when expressed individually in oocytes; however, all nine OSTalpha-OSTbeta combinations (i.e. OSTalpha-OSTbeta pairs from human, mouse, or skate) generated robust estrone 3-sulfate transport activity. Transport was sodium-independent, saturable, and inhibited by other steroids and anionic drugs. Human and mouse OSTalpha-OSTbeta also were able to mediate transport of taurocholate, digoxin, and prostaglandin E2 but not of estradiol 17beta-d-glucuronide or p-aminohippurate. OSTalpha and OSTbeta were able to reach the oocyte plasma membrane when expressed either individually or in pairs, indicating that co-expression is not required for proper membrane targeting. Interestingly, OSTalpha and OSTbeta mRNAs were highly expressed and widely distributed in human tissues, with the highest levels occurring in the testis, colon, liver, small intestine, kidney, ovary, and adrenal gland.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Conjugated estrogens Organic solute transporter subunit alpha Protein Humans UnknownSubstrateDetails Conjugated estrogens Organic solute transporter subunit beta Protein Humans UnknownSubstrateDetails Digoxin Organic solute transporter subunit alpha Protein Humans UnknownSubstrateDetails Digoxin Organic solute transporter subunit beta Protein Humans UnknownSubstrateDetails Dinoprostone Organic solute transporter subunit alpha Protein Humans UnknownSubstrateDetails Dinoprostone Organic solute transporter subunit beta Protein Humans UnknownSubstrateDetails Taurocholic acid Organic solute transporter subunit alpha Protein Humans UnknownSubstrateDetails Taurocholic acid Organic solute transporter subunit beta Protein Humans UnknownSubstrateDetails - Polypeptides
Name UniProt ID Organic solute transporter subunit alpha Q86UW1 Details Organic solute transporter subunit beta Q86UW2 Details