Mechanism of Cl- selection by a glutamate-gated chloride (GluCl) receptor revealed through mutations in the selectivity filter

The Journal of Biological Chemistry
Morten SunesenYoav Paas

Abstract

To learn about the mechanism of ion charge selectivity by invertebrate glutamate-gated chloride (GluCl) channels, we swapped segments between the GluClbeta receptor of Caenorhabditis elegans and the vertebrate cationic alpha7-acetylcholine receptor and monitored anionic/cationic permeability ratios. Complete conversion of the ion charge selectivity in a set of receptor microchimeras indicates that the selectivity filter of the GluClbeta receptor is created by a sequence connecting the first with the second transmembrane segments. A single substitution of a negatively charged residue within this sequence converted the selectivity of the GluClbeta receptor's pore from anionic to cationic. Unexpectedly, elimination of the charge of each basic residue of the selectivity filter, one at a time or concomitantly, moderately reduced the P(Cl)/P(Na) ratios, but the GluClbeta receptor's mutants retained high capacity to select Cl(-) over Na(+). These results indicate that, unlike the proposed case of anionic Gly- and gamma-aminobutyric acid-gated ion channels, positively charged residues do not play the key role in the selection of ionic charge by the GluClbeta receptor. Taken together with measurements of the effective open pore diameter...Continue Reading

References

Apr 1, 1992·Biophysical Journal·A Villarroel, B Sakmann
Oct 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·B W MatthewsW J Becktel
May 1, 1995·Trends in Pharmacological Sciences·G B Smith, R W Olsen
Jul 22, 1993·Proceedings. Biological Sciences·K Fatima-Shad, P H Barry
Sep 13, 1994·Proceedings of the National Academy of Sciences of the United States of America·N RundströmD Langosch
Jun 10, 1993·Nature
Dec 16, 1998·Science·C I Bargmann
Dec 3, 1999·The Journal of Physiology·V E WotringD S Weiss
Feb 12, 2002·Nature Reviews. Neuroscience·Arthur Karlin
May 1, 2002·The Journal of General Physiology·Andrew J MoorhousePeter H Barry
Aug 15, 2002·The Journal of Biological Chemistry·Marianne L JensenPhilip K Ahring
Mar 11, 2003·The Journal of Physiology·V E WotringD S Weiss
Jun 27, 2003·Nature·Atsuo MiyazawaNigel Unwin
Sep 13, 2003·British Journal of Pharmacology·Andrew J Thompson, Sarah C R Lummis
Nov 1, 2003·Annals of the New York Academy of Sciences·Sara FuchsEphraim Katchalski-Katzir
May 29, 2004·Trends in Neurosciences·Henry A LesterDennis A Dougherty
Aug 4, 2004·Progress in Biophysics and Molecular Biology·Angelo KeramidasPeter H Barry
Oct 26, 2005·Proceedings of the National Academy of Sciences of the United States of America·Yoav PaasBernard Attali

❮ Previous
Next ❯

Citations

Jun 26, 2009·Journal of Molecular Evolution·JacSue KehoeJonathan Bradley
Sep 21, 2010·Quarterly Reviews of Biophysics·Andrew J ThompsonSarah C R Lummis
Sep 2, 2009·Nature Reviews. Drug Discovery·Antoine TalyJean-Pierre Changeux
Jan 9, 2010·Annual Review of Pharmacology and Toxicology·Jean-Pierre Changeux
May 30, 2008·Frontiers in Bioscience : a Journal and Virtual Library·Gregg B Wells
Aug 15, 2013·British Journal of Pharmacology·Natascha SchaeferCarmen Villmann
Oct 30, 2016·Proceedings of the National Academy of Sciences of the United States of America·Gisela D Cymes, Claudio Grosman
Mar 5, 2010·Journal of Neurophysiology·Daniel JanssenEmmy Van Kerkhove
Aug 18, 2020·Journal of Chemical Information and Modeling·Grazia CottoneLuca Maragliano
Apr 1, 2021·Proceedings of the National Academy of Sciences of the United States of America·Gisela D Cymes, Claudio Grosman
Oct 24, 2012·The Journal of Physical Chemistry. B·Mary Hongying Cheng, Rob D Coalson

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.