Subunit-selective contribution to channel gating of the M4 domain of the nicotinic receptor

Biophysical Journal
Cecilia BouzatSteven M Sine

Abstract

The muscle nicotinic receptor (AChR) is a pentamer of four different subunits, each of which contains four transmembrane domains (M1-M4). We recently showed that channel opening and closing rates of the AChR depend on a hydrogen bond involving a threonine at position 14' of the M4 domain in the alpha-subunit. To determine whether residues in equivalent positions in non-alpha-subunits contribute to channel gating, we mutated deltaT14', betaT14', and epsilonS14' and evaluated changes in the kinetics of acetylcholine-activated currents. The mutation epsilonS14'A profoundly slows the rate of channel closing, an effect opposite to that produced by mutation of alphaT14'. Unlike mutations of alphaT14', epsilonS14'A does not affect the rate of channel opening. Mutations in deltaT14' and betaT14' do not affect channel opening or closing kinetics, showing that conserved residues are not functionally equivalent in all subunits. Whereas alphaT14'A and epsilonS14'A subunits contribute additively to the closing rate, they contribute nonadditively to the opening rate. Substitution of residues preserving the hydrogen bonding ability at position 14' produce nearly normal gating kinetics. Thus, we identify subunit-specific contributions to chann...Continue Reading

References

Aug 5, 1990·Journal of Molecular Biology·A Horovitz, A R Fersht
Aug 1, 1981·Pflügers Archiv : European journal of physiology·O P HamillF J Sigworth
Oct 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·S M Sine

❮ Previous
Next ❯

Citations

Sep 21, 2010·Quarterly Reviews of Biophysics·Andrew J ThompsonSarah C R Lummis
Aug 1, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Cecilia BouzatSteven M Sine
May 8, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Diego RayesCecilia Bouzat
Mar 11, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Natalia AndersenCecilia Bouzat
May 17, 2005·British Journal of Pharmacology·Paola V PlazasAna Belén Elgoyhen
Oct 10, 2006·Biophysical Journal·Jeremías CorradiCecilia Bouzat
Mar 8, 2006·The International Journal of Biochemistry & Cell Biology·Hugo R AriasCecilia Bouzat
Sep 16, 2009·The Journal of Physiology·Remigijus LapeLucia G Sivilotti
May 11, 2006·Annals of Neurology·Xin-Ming ShenAndrew G Engel
May 9, 2009·British Journal of Pharmacology·Guillermo SpitzmaulCecilia Bouzat
Jun 24, 2008·Annals of the New York Academy of Sciences·Steven M SineAndrew G Engel
Mar 21, 2015·Biochimica Et Biophysica Acta·John E BaenzigerJiayin Sun
Nov 27, 2007·Biochimica Et Biophysica Acta·María José De RosaCecilia Bouzat
Sep 24, 2004·Physiological Reviews·Joseph W Lynch
Jul 11, 2006·Molecular Pharmacology·Mariana BartosCecilia Bouzat
Jul 20, 2002·Molecular Pharmacology·María José De RosaCecilia Bouzat
Aug 25, 2005·Molecular Pharmacology·Diego RayesCecilia Bouzat
Feb 23, 2007·Molecular Pharmacology·Diego RayesCecilia Bouzat
Dec 12, 2003·Molecular Membrane Biology·Guillermo SpitzmaulCecilia Bouzat
Jan 24, 2007·The Journal of Biological Chemistry·José David Otero-CruzJosé Antonio Lasalde-Dominicci
Dec 11, 2014·Molecular Pharmacology·Leonardo DionisioCecilia Bouzat
Jul 13, 2004·The Journal of Biological Chemistry·Alejandro Ortiz-AcevedoJosé A Lasalde-Dominicci
Oct 15, 2011·Journal of Physiology, Paris·Cecilia Bouzat

❮ 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.