Functional characterization of ORCTL2--an organic cation transporter expressed in the renal proximal tubules.
Chromosome 11p15.5 harbors a gene or genes involved in Beckwith-Wiedemann syndrome that confer(s) susceptibility to Wilms' tumor, rhabdomyosarcoma, and hepatoblastoma. We have previously identified a transcript at 11p15.5 which encodes a putative membrane transport protein, designated organic cation transporter-like 2 (ORCTL2), that shares homology with tetracycline resistance proteins and bacterial multidrug resistance proteins. In this report, we have investigated the transport properties of ORCTL2 and show that this protein can confer resistance to chloroquine and quinidine when overexpressed in bacteria. Immunohistochemistry analyses performed with anti-ORCTL2 polyclonal antibodies on human renal sections indicate that ORCTL2 is localized on the apical membrane surface of the proximal tubules. These results suggest that ORCTL2 may play a role in the transport of chloroquine and quinidine related compounds in the kidney.
Reece
M
M
Department of Biochemistry, McGill University, Montreal, Que., Canada.
Prawitt
D
D
Landers
J
J
Kast
C
C
Gros
P
P
Housman
D
D
Zabel
B U
BU
Pelletier
J
J
D000818:Animals; D001419:Bacteria / Q000235:genetics; D001483:Base Sequence; D001506:Beckwith-Wiedemann Syndrome / Q000235:genetics*; D001692:Biological Transport; D019556:COS Cells; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D002738:Chloroquine / Q000493:pharmacokinetics; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D018432:Drug Resistance, Multiple / Q000235:genetics; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D007700:Kinetics; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D027701:Organic Cation Transport Proteins; D011802:Quinidine / Q000493:pharmacokinetics; D011994:Recombinant Proteins / Q000378:metabolism; D013752:Tetracycline / Q000493:pharmacokinetics; D013753:Tetracycline Resistance / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection
D002352:Carrier Proteins; D008565:Membrane Proteins; D009838:Oligodeoxyribonucleotides; D027701:Organic Cation Transport Proteins; D011994:Recombinant Proteins; C111653:SLC22A18 protein, human; D002738:Chloroquine; D013752:Tetracycline; D011802:Quinidine