Primary structure and functional expression of a cDNA encoding the bile canalicular, purine-specific Na(+)-nucleoside cotransporter.
We previously characterized a purine-specific Na(+)-nucleoside cotransport system in bile canalicular membrane. The function of this transport system may be related to conserving nucleosides and preventing cholestasis. We report here the isolation of a cDNA encoding a Na(+)-dependent nucleoside transporter from rat liver using an expression cloning strategy. The substrate specificities and kinetic characteristics of the cloned cotransporter are consistent with the properties of the Na(+)-dependent, purine-selective nucleoside transporter in bile canalicular membranes. The nucleotide sequence predicts a protein of 659 amino acids (72 kDa) with 14 putative membrane-spanning domains. Northern blot analysis showed that the transcripts are present in liver and several other tissues. Data base searches indicate significant sequence similarity to the pyrimidine-selective nucleoside transporter (cNT1) of rat jejunum. Although these two subtypes of Na(+)-nucleoside cotransporter have different substrate specificities and tissue localizations, they are members of a single gene family.
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Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Ortiz
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Arias
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D000595:Amino Acid Sequence; D000818:Animals; D001648:Bile Canaliculi / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D018076:DNA, Complementary / Q000737:chemistry*; D008297:Male; D008969:Molecular Sequence Data; D011684:Purine Nucleosides / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*; D027981:Symporters
D002352:Carrier Proteins; D018076:DNA, Complementary; D011684:Purine Nucleosides; D027981:Symporters; C073034:sodium-nucleoside cotransporter; D012964:Sodium