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Proc Natl Acad Sci U S A
1998 Aug 18;9517:9873-8. doi: 10.1073/pnas.95.17.9873.
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Cloning of Leishmania nucleoside transporter genes by rescue of a transport-deficient mutant.
Vasudevan G, Carter NS, Drew ME, Beverley SM, Sanchez MA, Seyfang A, Ullman B, Landfear SM.
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All parasitic protozoa studied to date are incapable of purine biosynthesis and must therefore salvage purine nucleobases or nucleosides from their hosts. This salvage process is initiated by purine transporters on the parasite cell surface. We have used a mutant line (TUBA5) of Leishmania donovani that is deficient in adenosine/pyrimidine nucleoside transport activity (LdNT1) to clone genes encoding these nucleoside transporters by functional rescue. Two such genes, LdNT1.1 and LdNT1.2, have been sequenced and shown to encode deduced polypeptides with significant sequence identity to the human facilitative nucleoside transporter hENT1. Hydrophobicity analysis of the LdNT1.1 and LdNT1.2 proteins predicted 11 transmembrane domains. Transfection of the adenosine/pyrimidine nucleoside transport-deficient TUBA5 parasites with vectors containing the LdNT1.1 and LdNT1.2 genes confers sensitivity to the cytotoxic adenosine analog tubercidin and concurrently restores the ability of this mutant line to take up [3H]adenosine and [3H]uridine. Moreover, expression of the LdNT1.2 ORF in Xenopus oocytes significantly increases their ability to take up [3H]adenosine, confirming that this single protein is sufficient to mediate nucleoside transport. These results establish genetically and biochemically that both LdNT1 genes encode functional adenosine/pyrimidine nucleoside transporters.
Altschul,
Basic local alignment search tool.
1990, Pubmed
Altschul,
Basic local alignment search tool.
1990,
Pubmed Aronow,
Two high affinity nucleoside transporters in Leishmania donovani.
1987,
Pubmed Callahan,
Heavy metal resistance: a new role for P-glycoproteins in Leishmania.
1991,
Pubmed Carter,
Arsenical-resistant trypanosomes lack an unusual adenosine transporter.
1993,
Pubmed Clayton,
Developmental regulation of nuclear gene expression in Trypanosoma brucei.
1992,
Pubmed Descoteaux,
A specialized pathway affecting virulence glycoconjugates of Leishmania.
1995,
Pubmed Flaspohler,
Functional identification of a Leishmania gene related to the peroxin 2 gene reveals common ancestry of glycosomes and peroxisomes.
1997,
Pubmed Griffiths,
Cloning of a human nucleoside transporter implicated in the cellular uptake of adenosine and chemotherapeutic drugs.
1997,
Pubmed
,
Xenbase Griffiths,
Molecular cloning and characterization of a nitrobenzylthioinosine-insensitive (ei) equilibrative nucleoside transporter from human placenta.
1997,
Pubmed
,
Xenbase Gueiros-Filho,
Selection against the dihydrofolate reductase-thymidylate synthase (DHFR-TS) locus as a probe of genetic alterations in Leishmania major.
1996,
Pubmed Hwang,
Creation of homozygous mutants of Leishmania donovani with single targeting constructs.
1996,
Pubmed Iovannisci,
High efficiency plating method for Leishmania promastigotes in semidefined or completely-defined medium.
1983,
Pubmed Iovannisci,
Genetic analysis of nucleoside transport in Leishmania donovani.
1984,
Pubmed Kapler,
Stable transfection of the human parasite Leishmania major delineates a 30-kilobase region sufficient for extrachromosomal replication and expression.
1990,
Pubmed Klamo,
Kinetics and stoichiometry of a proton/myo-inositol cotransporter.
1996,
Pubmed
,
Xenbase Lainson,
Epidemiology and ecology of leishmaniasis in Latin-America.
1978,
Pubmed Landfear,
Structure of mRNA encoded by tubulin genes in Leishmania enriettii.
1985,
Pubmed Langford,
Molecular characterization of two genes encoding members of the glucose transporter superfamily in the parasitic protozoan Leishmania donovani.
1992,
Pubmed Langford,
Functional expression of two glucose transporter isoforms from the parasitic protozoan Leishmania enriettii.
1994,
Pubmed
,
Xenbase Marger,
A major superfamily of transmembrane facilitators that catalyse uniport, symport and antiport.
1993,
Pubmed Marr,
Pyrazolopyrimidine metabolism in the pathogenic trypanosomatidae.
1983,
Pubmed Roberts,
Gene amplification and gene correction in somatic cells.
1982,
Pubmed Ryan,
Isolation of virulence genes directing surface glycosyl-phosphatidylinositol synthesis by functional complementation of Leishmania.
1993,
Pubmed Ryan,
Shuttle cosmid vectors for the trypanosomatid parasite Leishmania.
1993,
Pubmed Seyfang,
Aspartate 19 and glutamate 121 are critical for transport function of the myo-inositol/H+ symporter from Leishmania donovani.
1997,
Pubmed
,
Xenbase Vieira,
Chloride conductive pathways which support electrogenic H+ pumping by Leishmania major promastigotes.
1995,
Pubmed Walsh,
Selective primary health care: an interim strategy for disease control in developing countries.
1979,
Pubmed Williams,
A mammalian delayed-early response gene encodes HNP36, a novel, conserved nucleolar protein.
1995,
Pubmed Yao,
Molecular cloning and functional characterization of nitrobenzylthioinosine (NBMPR)-sensitive (es) and NBMPR-insensitive (ei) equilibrative nucleoside transporter proteins (rENT1 and rENT2) from rat tissues.
1997,
Pubmed
,
Xenbase Zilberstein,
Maintenance of cytoplasmic pH and proton motive force in promastigotes of Leishmania donovani.
1989,
Pubmed
