PMID: 11181831Feb 22, 2001Paper

A single beta subunit M2 domain residue controls the picrotoxin sensitivity of alphabeta heteromeric glycine receptor chloride channels

Journal of Neurochemistry
Q ShanJ W Lynch

Abstract

This study investigated the residues responsible for the reduced picrotoxin sensitivity of the alphabeta heteromeric glycine receptor relative to the alpha homomeric receptor. By analogy with structurally related receptors, the beta subunit M2 domain residues P278 and F282 were considered the most likely candidates for mediating this effect. These residues align with G254 and T258 of the alpha subunit. The T258A, T258C and T258F mutations dramatically reduced the picrotoxin sensitivity of the alpha homomeric receptor. Furthermore, the converse F282T mutation in the beta subunit increased the picrotoxin sensitivity of the alphabeta heteromeric receptor. The P278G mutation in the beta subunit did not affect the picrotoxin sensitivity of the alphabeta heteromer. Thus, a ring of five threonines at the M2 domain depth corresponding to alpha subunit T258 is specifically required for picrotoxin sensitivity. Mutations to alpha subunit T258 also profoundly influenced the apparent glycine affinity. A substituted cysteine accessibility analysis revealed that the T258C sidechain increases its pore exposure in the channel open state. This provides further evidence for an allosteric mechanism of picrotoxin inhibition, but renders it unlikely...Continue Reading

References

Sep 22, 1992·Proceedings. Biological Sciences·A VillarroelB Sakmann
Nov 1, 1992·Neuroreport·A Devillers-ThiéryD Bertrand
Oct 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·D LangoschH Betz
Aug 1, 1987·Molecular and Cellular Biology·C Chen, H Okayama
Aug 1, 1981·Pflügers Archiv : European journal of physiology·O P HamillF J Sigworth
Nov 1, 1993·The Journal of Membrane Biology·A Devillers-ThiéryJ P Changeux
Sep 13, 1994·Proceedings of the National Academy of Sciences of the United States of America·N RundströmD Langosch
Jun 3, 1993·Nature·R H Ffrench-ConstantA E Chalmers
Dec 5, 1995·Proceedings of the National Academy of Sciences of the United States of America·T L WangG R Cutting
Dec 5, 1995·Proceedings of the National Academy of Sciences of the United States of America·D ZhangS A Lipton
Jan 1, 1997·Pharmacology & Therapeutics·S RajendraP R Schofield
Aug 26, 1998·Methods in Enzymology·A Karlin, M H Akabas

❮ Previous
Next ❯

Citations

Oct 15, 2009·Journal of Neural Transmission·Marina Sorrentino Hernandes, Lanfranco R P Troncone
Sep 21, 2010·Quarterly Reviews of Biophysics·Andrew J ThompsonSarah C R Lummis
Jul 31, 2007·Visual Neuroscience·Ping Li, Malcolm Slaughter
Sep 20, 2012·Chemical Reviews·Damien LemoineThomas Grutter
May 8, 2002·The European Journal of Neuroscience·Laurent NguyenJean-Michel Rigo
Apr 21, 2011·Molecular Pharmacology·A J ThompsonS C R Lummis
Sep 23, 2006·The Journal of Physiology·Anna SedelnikovaDavid S Weiss
Jun 30, 2006·Journal of Neurochemistry·Rebecca HawthorneJoseph W Lynch
Aug 30, 2005·Neuropharmacology·Elena L KondratskayaBodo Laube
Mar 5, 2017·British Journal of Pharmacology·Moawiah M NaffaaJane R Hanrahan
Sep 24, 2004·Physiological Reviews·Joseph W Lynch
Mar 1, 2005·The European Journal of Neuroscience·Anniina AlakuijalaMichael Pasternack
Aug 20, 2005·The Journal of Biological Chemistry·Rebecca Hawthorne, Joseph W Lynch
Nov 1, 2011·British Journal of Pharmacology·Robiul Islam, Joseph W Lynch
Oct 20, 2012·Neuroreport·Ping Li, Malcolm M Slaughter
Aug 15, 2013·British Journal of Pharmacology·Natascha SchaeferCarmen Villmann
Sep 20, 2002·The Journal of Biological Chemistry·Qiang ShanJoseph W Lynch
May 13, 2003·The Journal of Biological Chemistry·Simon T NevinJoseph W Lynch
Apr 30, 2016·British Journal of Pharmacology·Cesar O LaraGonzalo E Yévenes
Apr 9, 2005·The Journal of Pharmacology and Experimental Therapeutics·Paromita Das, Glenn H Dillon
Jul 29, 2020·Nature Communications·Arvind KumarSudha Chakrapani
Apr 22, 2009·Neurochemical Research·Nathan L AbsalomTrevor M Lewis
Sep 2, 2014·Parasite : Journal De La Société Française De Parasitologie·José Miguel Flores-FernándezMoisés Martínez-Velázquez
Jun 1, 2017·Frontiers in Molecular Neuroscience·Galyna MaleevaPiotr Bregestovski
Dec 14, 2005·The Journal of Biological Chemistry·Dian-Shi WangPascal Legendre

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.