title: Glutamine uptake by neurons: interaction of protons with system a transporters.
abstract: Astrocytes provide the glutamine required by neurons to synthesize glutamate and GABA. However, the mechanisms involved in glutamine transfer from glia to neurons have remained poorly understood. Recent work has implicated the System N transporter SN1 in the efflux of glutamine from astrocytes and the very closely related System A transporters SA1 and SA2 in glutamine uptake by neurons. To understand how these closely related proteins mediate flux in different directions, we have examined their ionic coupling. In contrast to the electroneutral exchange of H+ for Na+ and neutral amino acid catalyzed by SN1, we now show that SA1 and SA2 do not couple H+ movement to amino acid flux. As a result, SA1 and SA2 are electrogenic and do not mediate flux reversal as readily as SN1. Differences between System N and A transporters in coupling to H+ thus contribute to the delivery of glutamine from glia to neurons. Nonetheless, although they are not transported, H+ inhibit SA1 and SA2 by competing with Na+.
authors.affiliation: Department of Neurology, University of California San Francisco School of Medicine, San Francisco, California 94143-0435, USA.
authors.forename: Farrukh A
authors.initials: FA
authors.lastname: Chaudhry
authors.forename: Dietmar
authors.initials: D
authors.lastname: Schmitz
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Reimer
authors.forename: Peter
authors.initials: P
authors.lastname: Larsson
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Gray
authors.forename: Roger
authors.initials: R
authors.lastname: Nicoll
authors.forename: Michael
authors.initials: M
authors.lastname: Kavanaugh
authors.forename: Robert H
authors.initials: RH
authors.lastname: Edwards
mesh_terms: D026924:Amino Acid Transport System A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D026921:Amino Acid Transport Systems, Neutral; D000818:Animals; D001667:Binding, Competitive / Q000502:physiology; D001692:Biological Transport / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D005973:Glutamine / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D006624:Hippocampus; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D009433:Neural Inhibition / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009928:Organ Specificity; D011485:Protein Binding / Q000502:physiology; D011522:Protons; D051381:Rats; D012964:Sodium / Q000378:metabolism; D014162:Transfection; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D026924:Amino Acid Transport System A; D026921:Amino Acid Transport Systems, Neutral; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D011522:Protons; C445761:SLC38A1 protein, human; C498797:SLC38A2 protein, human; C486716:Slc38a1 protein, rat; C412568:Slc38a2 protein, rat; C403222:system N protein 1; D005973:Glutamine; D015091:beta-Alanine; C012924:2,2-dimethyl-beta-alanine; D012964:Sodium