title: The sodium-coupled neutral amino acid transporter SNAT2 mediates an anion leak conductance that is differentially inhibited by transported substrates.
abstract: The sodium-coupled neutral amino acid transporter SNAT2 mediates cellular uptake of glutamine and other small, neutral amino acids. Here, we report the existence of a leak anion pathway associated with SNAT2. The leak anion conductance was increased by, but did not require the presence of, extracellular sodium. The transported substrates L-alanine, L-glutamine, and alpha-(methylamino)isobutyrate inhibited the anion leak conductance, each with different potency. A transporter with the mutation H-304A did not catalyze alanine transport but still catalyzed anion leak current, demonstrating that substrate transport is not required for anion current inhibition. Both the substrate and Na+ were able to bind to the SNAT2H-304A transporter normally. The selectivity sequence of the SNAT2H-304A anion conductance was SCN->>NO3->I->Br->Cl->Mes-. Anion flux mediated by the more hydrophobic anion SCN- was not saturable, whereas nitrate flux demonstrated saturation kinetics with an apparent Km of 29 mM. SNAT2, which belongs to the SLC38 family of transporters, has to be added to the growing number of secondary, Na+-coupled transporters catalyzing substrate-gated or leak anion conductances. Therefore, we can speculate that such anion-conducting pathways are general features of Na+-transporting systems.
authors.affiliation: University of Miami School of Medicine, Miami, Florida 33136, USA.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhang
authors.forename: Christof
authors.initials: C
authors.lastname: Grewer
mesh_terms: D026924:Amino Acid Transport System A / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism*; D000838:Anions; D002460:Cell Line; D004553:Electric Conductivity; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D007668:Kidney / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*
chemical_list: D026924:Amino Acid Transport System A; D000596:Amino Acids; D000838:Anions; C498797:SLC38A2 protein, human; D012964:Sodium