title: Equilibrative nucleoside transporter family members from Leishmania donovani are electrogenic proton symporters.
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. LdNT1.1, 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.
authors.affiliation: Vollum Institute, Oregon Health & Science University, Portland, Oregon 97239-3098, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Stein
authors.forename: Gayatri
authors.initials: G
authors.lastname: Vaseduvan
authors.forename: Nicola S
authors.initials: NS
authors.lastname: Carter
authors.forename: Buddy
authors.initials: B
authors.lastname: Ullman
authors.forename: Scott M
authors.initials: SM
authors.lastname: Landfear
authors.forename: Michael P
authors.initials: MP
authors.lastname: Kavanaugh
mesh_terms: D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004176:Dipyridamole / Q000493:pharmacokinetics; D006151:Guanosine / Q000378:metabolism*; D007288:Inosine / Q000378:metabolism*; D007700:Kinetics; D007893:Leishmania donovani / Q000378:metabolism*; D033703:Nucleoside Transport Proteins / Q000378:metabolism*; D011522:Protons; D015800:Protozoan Proteins / Q000378:metabolism*; D012964:Sodium / Q000494:pharmacology; D013379:Substrate Specificity
chemical_list: C114230:LdNT1 protein, Leishmania donovani; C411852:LdNT2 protein, Leishmania donovani; D033703:Nucleoside Transport Proteins; D011522:Protons; D015800:Protozoan Proteins; D006151:Guanosine; D000249:Adenosine Monophosphate; D007288:Inosine; D004176:Dipyridamole; D012964:Sodium