PMID: 9435265Jan 22, 1998Paper

Molecular determinant of ion selectivity of a (Na+ + K+)-coupled rat brain glutamate transporter

Proceedings of the National Academy of Sciences of the United States of America
Y ZhangB I Kanner

Abstract

Glutamate transporters remove this neurotransmitter from the synaptic cleft by a two-stage electrogenic process, in which glutamate is first cotransported with three sodium ions and a proton. Subsequently, the cycle is completed by translocation of a potassium ion in the opposite direction. Recently, we have identified an amino acid residue of the glutamate transporter GLT-1 (Glu-404) that influences potassium coupling. We have now analyzed the effect of seven other amino acid residues in the highly conserved region surrounding this site. One of these residues, Tyr-403, also proved important for potassium coupling, because mutation to Phe (Y403F) resulted in an electroneutral obligate exchange mode of glutamate transport. This mutation in the transporter also caused an approximately 8-fold increase in the apparent sodium affinity, with no change in the apparent affinity for L-glutamate or D-aspartate. Strikingly, although exchange catalyzed by the wild-type transporter is strictly dependent on sodium, the selectivity of Y403F mutant transporters is altered so that sodium can be replaced by other alkaline metal cations including lithium and cesium. These results indicate the presence of interacting sites in or near the transport...Continue Reading

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Citations

Nov 26, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·A W WolkoffB F Scharschmidt
Apr 10, 2007·The Journal of Membrane Biology·Baruch I Kanner
Nov 13, 2003·European Journal of Pharmacology·Yoshikatsu Kanai, Matthias A Hediger
May 23, 2001·Progress in Neurobiology·N C Danbolt
Sep 12, 2001·Trends in Biochemical Sciences·D J SlotboomJ S Lolkema
Sep 10, 2013·Nature Structural & Molecular Biology·Sonja JensenDirk Jan Slotboom
Oct 8, 2013·Nature Structural & Molecular Biology·Baruch I Kanner
Aug 27, 2009·Proceedings of the National Academy of Sciences of the United States of America·Shlomit TeichmanBaruch I Kanner
Apr 29, 2010·The Journal of Biological Chemistry·Noa Rosental, Baruch I Kanner
Nov 26, 2010·The Journal of Biological Chemistry·Ariane LeinenweberChristoph Fahlke
Aug 6, 2008·The Journal of Biological Chemistry·Indira H ShrivastavaIvet Bahar
May 31, 2007·The Journal of General Physiology·Shlomit Teichman, Baruch I Kanner
Jan 22, 2005·Journal of Bacteriology·Svetlana N Yurgel, Michael L Kahn
May 20, 1999·Annual Review of Pharmacology and Toxicology·R P Seal, S G Amara
Mar 20, 2014·PloS One·Germano Heinzelmann, Serdar Kuyucak
Dec 10, 1999·Proceedings of the National Academy of Sciences of the United States of America·D J SlotboomJ S Lolkema
Dec 26, 2001·Proceedings of the National Academy of Sciences of the United States of America·R P SealS G Amara
Feb 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·Y Zhang, B I Kanner
Aug 17, 2010·Neuropharmacology·Jie Jiang, Susan G Amara
Sep 18, 2004·FEMS Microbiology Reviews·Svetlana N Yurgel, Michael L Kahn
Oct 20, 2001·The Journal of Veterinary Medical Science·K SatoK Kagota
Jul 23, 2004·The Journal of Chemical Physics·Timothy D Vaden, James M Lisy
Aug 1, 2006·The Journal of Biological Chemistry·Barbara H LeightonSusan G Amara
Nov 5, 2003·The Journal of Biological Chemistry·Lars Borre, Baruch I Kanner
Nov 2, 2017·The Journal of General Physiology·Valentina ArkhipovaDirk-Jan Slotboom
Jun 1, 2006·American Journal of Physiology. Renal Physiology·Yohannes HagosBirgitta C Burckhardt
Dec 17, 2008·The Journal of Biological Chemistry·Shiwei HuangRobert J Vandenberg
Oct 19, 2013·Physiological Reviews·Robert J Vandenberg, Renae M Ryan

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