Primary structure and functional characterization of a high-affinity glutamate transporter.
Glutamate transport across plasma membranes of neurons, glial cells and epithelial cells of the small intestine and kidney proceeds by high- and low-affinity transport systems. High-affinity (Km 2-50 microM) transport systems have been described that are dependent on Na+ but not Cl- ions and have a preference for L-glutamate and D- and L-aspartate. In neurons high-affinity glutamate transporters are essential for terminating the postsynaptic action of glutamate by rapidly removing released glutamate from the synaptic cleft. We have isolated a complementary DNA encoding an electrogenic Na(+)- but not Cl(-)-dependent high-affinity glutamate transporter (named EAAC1) from rabbit small intestine by expression in Xenopus oocytes. We find EAAC1 transcripts in specific neuronal structures in the central nervous system as well as in the small intestine, kidney, liver and heart. The function and pharmacology of the expressed protein are characteristic of the high-affinity glutamate transporter already identified in neuronal tissues. The abnormal glutamate transport that is associated with certain neurodegenerative diseases and which occurs during ischaemia and anoxia could be due to abnormalities in the function of this protein.
D000595:Amino Acid Sequence; D027322:Amino Acid Transport System X-AG; D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005971:Glutamates / Q000378:metabolism*; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism*; D017403:In Situ Hybridization; D007421:Intestine, Small / Q000378:metabolism*; D007583:Jejunum / Q000378:metabolism; D007700:Kinetics; D008961:Models, Structural; D008969:Molecular Sequence Data; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009838:Oligodeoxyribonucleotides; D009865:Oocytes / Q000502:physiology; D016366:Open Reading Frames; D009928:Organ Specificity; D011487:Protein Conformation; D012313:RNA / Q000032:analysis / Q000235:genetics / Q000302:isolation & purification; D015347:RNA Probes; D011817:Rabbits; D014981:Xenopus
D027322:Amino Acid Transport System X-AG; D005971:Glutamates; D006023:Glycoproteins; D009838:Oligodeoxyribonucleotides; D015347:RNA Probes; D012313:RNA; D004247:DNA