An excitatory amino-acid transporter with properties of a ligand-gated chloride channel.
Excitatory amino-acid transporters (EAATs) in the central nervous system maintain extracellular glutamate concentrations below excitotoxic levels and may limit the activation of glutamate receptors. Here we report the cloning of a novel human aspartate/glutamate transporter, EAAT4, which is expressed predominantly in the cerebellum. The transport activity encoded by EAAT4 has high apparent affinity for L-aspartate and L-glutamate, and has a pharmacological profile consistent with previously described cerebellar transport activities. In Xenopus oocytes expressing EAAT4, L-aspartate and L-glutamate elicited a current predominantly carried by chloride ions. This chloride conductance was not blocked by components that block endogenous oocyte chloride channels. Thus EAAT4 combines the re-uptake of neurotransmitter with a mechanism for increasing chloride permeability, both of which could regulate excitatory neurotransmission.
Fairman
W A
WA
Howard Hughes Medical Institute, Oregon Health Sciences University, Portland 97201, USA.
Vandenberg
R J
RJ
Arriza
J L
JL
Kavanaugh
M P
MP
Amara
S G
SG
D000595:Amino Acid Sequence; D027322:Amino Acid Transport System X-AG; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001483:Base Sequence; D002478:Cells, Cultured; D002531:Cerebellum / Q000378:metabolism*; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D018076:DNA, Complementary; D050581:Excitatory Amino Acid Transporter 4; D050491:Glutamate Plasma Membrane Transport Proteins; D006801:Humans; D015640:Ion Channel Gating; D008024:Ligands; D008564:Membrane Potentials; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D017459:Receptors, Amino Acid / Q000235:genetics / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D012964:Sodium / Q000378:metabolism; D027981:Symporters; D014981:Xenopus
D027322:Amino Acid Transport System X-AG; D018118:Chloride Channels; D002712:Chlorides; D018076:DNA, Complementary; D050581:Excitatory Amino Acid Transporter 4; D050491:Glutamate Plasma Membrane Transport Proteins; D008024:Ligands; D017459:Receptors, Amino Acid; D017470:Receptors, Glutamate; C493391:SLC1A6 protein, human; D027981:Symporters; C031959:aspartic acid receptor; D001224:Aspartic Acid; D012964:Sodium