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Cell Mol Life Sci
2018 Jul 01;7513:2457-2471. doi: 10.1007/s00018-017-2741-4.
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Molecular function of the novel α7β2 nicotinic receptor.
Nielsen BE
,
Minguez T
,
Bermudez I
,
Bouzat C
.
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The α7 nicotinic receptor is a promising drug target for neurological and inflammatory disorders. Although it is the homomeric member of the family, a novel α7β2 heteromeric receptor has been discovered. To decipher the functional contribution of the β2 subunit, we generated heteromeric receptors with fixed stoichiometry by two different approaches comprising concatenated and unlinked subunits. Receptors containing up to three β2 subunits are functional. As the number of β2 subunits increases in the pentameric arrangement, the durations of channel openings and activation episodes increase progressively probably due to decreased desensitization. The prolonged activation episodes conform the kinetic signature of α7β2 and may have an impact on neuronal excitability. For activation of α7β2 receptors, an α7/α7 binding-site interface is required, thus indicating that the three β2 subunits are located consecutively in the pentameric arrangement. α7-positive allosteric modulators (PAMs) are emerging as novel therapeutic drugs. The presence of β2 in the pentamer affects neither type II PAM potentiation nor activation by an allosteric agonist whereas it impairs type I PAM potentiation. This first single-channel study provides fundamental basis required to decipher the role and function of the novel α7β2 receptor and opens doors to develop selective therapeutic drugs.
Andersen,
Stoichiometry for activation of neuronal α7 nicotinic receptors.
2013, Pubmed
Andersen,
Stoichiometry for activation of neuronal α7 nicotinic receptors.
2013,
Pubmed
Andersen,
Exploring the positive allosteric modulation of human α7 nicotinic receptors from a single-channel perspective.
2016,
Pubmed
Andersen,
Functional relationships between agonist binding sites and coupling regions of homomeric Cys-loop receptors.
2011,
Pubmed
Arias,
Positive and negative modulation of nicotinic receptors.
2010,
Pubmed
Aryal,
Hydrophobic gating in ion channels.
2015,
Pubmed
Benallegue,
The additional ACh binding site at the α4(+)/α4(-) interface of the (α4β2)2α4 nicotinic ACh receptor contributes to desensitization.
2013,
Pubmed
,
Xenbase
Bertrand,
Allosteric modulation of nicotinic acetylcholine receptors.
2007,
Pubmed
Bouzat,
Structural basis of the different gating kinetics of fetal and adult acetylcholine receptors.
1994,
Pubmed
Bouzat,
Molecular function of α7 nicotinic receptors as drug targets.
2018,
Pubmed
Bouzat,
The interface between extracellular and transmembrane domains of homomeric Cys-loop receptors governs open-channel lifetime and rate of desensitization.
2008,
Pubmed
Bouzat,
Nicotinic acetylcholine receptors at the single-channel level.
2018,
Pubmed
Carbone,
Pentameric concatenated (alpha4)(2)(beta2)(3) and (alpha4)(3)(beta2)(2) nicotinic acetylcholine receptors: subunit arrangement determines functional expression.
2009,
Pubmed
,
Xenbase
Changeux,
Nicotinic receptors, allosteric proteins and medicine.
2008,
Pubmed
Chatzidaki,
Allosteric modulation of nicotinic acetylcholine receptors.
2015,
Pubmed
Corradi,
Single-channel kinetic analysis for activation and desensitization of homomeric 5-HT(3)A receptors.
2009,
Pubmed
Corradi,
Understanding the Bases of Function and Modulation of α7 Nicotinic Receptors: Implications for Drug Discovery.
2016,
Pubmed
Dineley,
Nicotinic ACh receptors as therapeutic targets in CNS disorders.
2015,
Pubmed
Ericksen,
Tandem couture: Cys-loop receptor concatamer insights and caveats.
2007,
Pubmed
Freedman,
α7-nicotinic acetylcholine receptor agonists for cognitive enhancement in schizophrenia.
2014,
Pubmed
Gill,
Agonist activation of alpha7 nicotinic acetylcholine receptors via an allosteric transmembrane site.
2011,
Pubmed
,
Xenbase
Gill,
Contrasting properties of α7-selective orthosteric and allosteric agonists examined on native nicotinic acetylcholine receptors.
2013,
Pubmed
Hassaine,
X-ray structure of the mouse serotonin 5-HT3 receptor.
2014,
Pubmed
Hurst,
A novel positive allosteric modulator of the alpha7 neuronal nicotinic acetylcholine receptor: in vitro and in vivo characterization.
2005,
Pubmed
,
Xenbase
Kabbani,
Are nicotinic acetylcholine receptors coupled to G proteins?
2013,
Pubmed
Kelley,
A cytoplasmic region determines single-channel conductance in 5-HT3 receptors.
2003,
Pubmed
Liu,
Functional α7β2 nicotinic acetylcholine receptors expressed in hippocampal interneurons exhibit high sensitivity to pathological level of amyloid β peptides.
2012,
Pubmed
Liu,
A novel nicotinic acetylcholine receptor subtype in basal forebrain cholinergic neurons with high sensitivity to amyloid peptides.
2009,
Pubmed
,
Xenbase
Liu,
A novel nicotinic mechanism underlies β-amyloid-induced neuronal hyperexcitation.
2013,
Pubmed
Mazzaferro,
Additional acetylcholine (ACh) binding site at alpha4/alpha4 interface of (alpha4beta2)2alpha4 nicotinic receptor influences agonist sensitivity.
2011,
Pubmed
,
Xenbase
Mazzaferro,
α4β2 Nicotinic Acetylcholine Receptors: RELATIONSHIPS BETWEEN SUBUNIT STOICHIOMETRY AND FUNCTION AT THE SINGLE CHANNEL LEVEL.
2017,
Pubmed
Moretti,
The novel α7β2-nicotinic acetylcholine receptor subtype is expressed in mouse and human basal forebrain: biochemical and pharmacological characterization.
2014,
Pubmed
,
Xenbase
Moroni,
Non-agonist-binding subunit interfaces confer distinct functional signatures to the alternate stoichiometries of the alpha4beta2 nicotinic receptor: an alpha4-alpha4 interface is required for Zn2+ potentiation.
2008,
Pubmed
,
Xenbase
Mowrey,
Insights into distinct modulation of α7 and α7β2 nicotinic acetylcholine receptors by the volatile anesthetic isoflurane.
2013,
Pubmed
Murray,
α7β2 nicotinic acetylcholine receptors assemble, function, and are activated primarily via their α7-α7 interfaces.
2012,
Pubmed
,
Xenbase
Nelson,
Alternate stoichiometries of alpha4beta2 nicotinic acetylcholine receptors.
2003,
Pubmed
,
Xenbase
Nordman,
An interaction between α7 nicotinic receptors and a G-protein pathway complex regulates neurite growth in neural cells.
2012,
Pubmed
Paulo,
Proteomic analysis of an alpha7 nicotinic acetylcholine receptor interactome.
2009,
Pubmed
Pałczyńska,
Activation of α7 nicotinic receptors by orthosteric and allosteric agonists: influence on single-channel kinetics and conductance.
2012,
Pubmed
,
Xenbase
Rayes,
Number and locations of agonist binding sites required to activate homomeric Cys-loop receptors.
2009,
Pubmed
Revah,
Mutations in the channel domain alter desensitization of a neuronal nicotinic receptor.
1991,
Pubmed
,
Xenbase
Shytle,
Cholinergic modulation of microglial activation by alpha 7 nicotinic receptors.
2004,
Pubmed
Thomsen,
α7 and β2 Nicotinic Acetylcholine Receptor Subunits Form Heteromeric Receptor Complexes that Are Expressed in the Human Cortex and Display Distinct Pharmacological Properties.
2015,
Pubmed
,
Xenbase
Thomsen,
Cognitive improvement by activation of alpha7 nicotinic acetylcholine receptors: from animal models to human pathophysiology.
2010,
Pubmed
Uteshev,
The therapeutic promise of positive allosteric modulation of nicotinic receptors.
2014,
Pubmed
Wallace,
Targeting the nicotinic alpha7 acetylcholine receptor to enhance cognition in disease.
2011,
Pubmed
Williams,
Positive allosteric modulators as an approach to nicotinic acetylcholine receptor-targeted therapeutics: advantages and limitations.
2011,
Pubmed
Wu,
Heteromeric α7β2 Nicotinic Acetylcholine Receptors in the Brain.
2016,
Pubmed
Young,
Potentiation of alpha7 nicotinic acetylcholine receptors via an allosteric transmembrane site.
2008,
Pubmed
,
Xenbase
Zwart,
Unique pharmacology of heteromeric α7β2 nicotinic acetylcholine receptors expressed in Xenopus laevis oocytes.
2014,
Pubmed
,
Xenbase
daCosta,
Single-channel and structural foundations of neuronal α7 acetylcholine receptor potentiation.
2011,
Pubmed
daCosta,
Stoichiometry for drug potentiation of a pentameric ion channel.
2013,
Pubmed
daCosta,
Stoichiometry for α-bungarotoxin block of α7 acetylcholine receptors.
2015,
Pubmed
