Equilibrative nucleoside transporter family members from Leishmania donovani are electrogenic proton symporters

Alex Stein, Gayatri Vaseduvan, Nicola Carter, Buddy Ullman, Scott Landfear, Michael P. Kavanaugh

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Leishmania donovani express two members of the equilibrative nucleoside transporter family; LdNT1 encoded by two closely related and linked genes, LdNT1.1 and LdNT1.2, that transport adenosine and pyrimidine nucleosides and LdNT2 that transports inosine and guanosine exclusively. LdNTI.1, LdNT1.2, and LdNT2 have been expressed in Xenopus laevis oocytes and found to be electrogenic in the presence of nucleoside ligands for which they mediate transport. Further analysis revealed that ligand uptake and transport currents through LdNT1-type transporters are proton-dependent. In addition to the flux of protons that is coupled to the transport reaction, LdNT1 transporters mediate a variable constitutive proton conductance that is blocked by substrates and dipyridamole. Surprisingly, LdNT1.1 and LdNT1.2 exhibit different electrogenic properties, despite their close sequence homology. This electrophysiological study provides the first demonstration that members of the equilibrative nucleoside transporter family can be electrogenic and establishes that these three permeases, unlike their mammalian counterparts, are probably concentrative rather than facilitative transporters.

Original languageEnglish (US)
Pages (from-to)35127-35134
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number37
DOIs
StatePublished - Sep 12 2003

Fingerprint

Nucleoside Transport Proteins
Symporters
Leishmania donovani
Protons
Pyrimidine Nucleosides
Ligands
Inosine
Membrane Transport Proteins
Dipyridamole
Guanosine
Xenopus laevis
Sequence Homology
Nucleosides
Adenosine
Oocytes
Demonstrations
Genes
Fluxes
Substrates

ASJC Scopus subject areas

  • Biochemistry

Cite this

Equilibrative nucleoside transporter family members from Leishmania donovani are electrogenic proton symporters. / Stein, Alex; Vaseduvan, Gayatri; Carter, Nicola; Ullman, Buddy; Landfear, Scott; Kavanaugh, Michael P.

In: Journal of Biological Chemistry, Vol. 278, No. 37, 12.09.2003, p. 35127-35134.

Research output: Contribution to journalArticle

Stein, Alex ; Vaseduvan, Gayatri ; Carter, Nicola ; Ullman, Buddy ; Landfear, Scott ; Kavanaugh, Michael P. / Equilibrative nucleoside transporter family members from Leishmania donovani are electrogenic proton symporters. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 37. pp. 35127-35134.
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