ArticleThe Journal of biological chemistry2016
Differential α4(+)/(-)β2 Agonist-binding Site Contributions to α4β2 Nicotinic Acetylcholine Receptor Function within and between Isoforms.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
- The Human Alpha3 Beta2 Neuronal Nicotinic Acetylcholine Receptor Can Form Two Distinguishable Subtypes.International journal of molecular sciences · 2025Article
- Alterations in Neuronal Nicotinic Acetylcholine Receptors in the Pathogenesis of Various Cognitive Impairments.CNS neuroscience & therapeutics · 2024Review
- Neuronal nicotinic acetylcholine receptor antibodies in autoimmune central nervous system disorders.Frontiers in immunology · 2024Article
- A potential cost of evolving epibatidine resistance in poison frogs.BMC biology · 2023Article
- SARS-CoV-2 spike ectodomain targets α7 nicotinic acetylcholine receptors.The Journal of biological chemistry · 2023Article
- Pharmacological characterization of 5-iodo-A-85380, a β2-selective nicotinic receptor agonist, in mice.Journal of psychopharmacology (Oxford, England) · 2022Article
- Coffee and cigarettes: Modulation of high and low sensitivity α4β2 nicotinic acetylcholine receptors by n-MP, a biomarker of coffee consumption.Neuropharmacology · 2022Article
- Concatemers to re-investigate the role of α5 in α4β2 nicotinic receptors.Cellular and molecular life sciences : CMLS · 2021Article
- Nicotinic Acetylcholine Receptor Accessory Subunits Determine the Activity Profile of Epibatidine Derivatives.Molecular pharmacology · 2020Article
- Heterologous expression of concatenated nicotinic ACh receptors: Pros and cons of subunit concatenation and recommendations for construct designs.British journal of pharmacology · 2020Article
- A novel fast-channel myasthenia caused by mutation in β subunit of AChR reveals subunit-specific contribution of the intracellular M1-M2 linker to channel gating.Experimental neurology · 2020Article
- Nicotinic acetylcholine receptors: Conventional and unconventional ligands and signaling.Neuropharmacology · 2020Review
- Heteromeric Neuronal Nicotinic Acetylcholine Receptors with MutantThe Journal of pharmacology and experimental therapeutics · 2019Article
- Potentiation of a neuronal nicotinic receptor via pseudo-agonist site.Cellular and molecular life sciences : CMLS · 2019Article
- Distinctive single-channel properties of α4β2-nicotinic acetylcholine receptor isoforms.PloS one · 2019Article
- Article
- The fifth subunit of the (α4β2)British journal of pharmacology · 2018Article
- Molecular and cellular characterization of nicotinic acetylcholine receptor subtypes in the arcuate nucleus of the mouse hypothalamus.The European journal of neuroscience · 2018Article
- Concatenated nicotinic acetylcholine receptors: A gift or a curse?The Journal of general physiology · 2018Article
- Interacting amino acid replacements allow poison frogs to evolve epibatidine resistance.Science (New York, N.Y.) · 2017Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Two α4β2 nicotinic acetylcholine receptor (α4β2-nAChR) isoforms exist with (α4)2(β2)3 and (α4)3(β2)2 subunit stoichiometries and high versus low agonist sensitivities (HS and LS), respectively. Both isoforms contain a pair of α4(+)/(-)β2 agonist-binding sites. The LS isoform also contains a unique α4(+)/(-)α4 site with lower agonist affinity than the α4(+)/(-)β2 sites. However, the relative roles of the conserved α4(+)/(-)β2 agonist-binding sites in and between the isoforms have not been studied. We used a fully linked subunit concatemeric nAChR approach to express pure populations of HS or LS isoform α4β2*-nAChR. This approach also allowed us to mutate individual subunit interfaces, or combinations thereof, on each isoform background. We used this approach to systematically mutate a triplet of β2 subunit (-)-face E-loop residues to their non-conserved α4 subunit counterparts or vice versa (β2HQT and α4VFL, respectively). Mutant-nAChR constructs (and unmodified controls) were expressed in Xenopus oocytes. Acetylcholine concentration-response curves and maximum function were measured using two-electrode voltage clamp electrophysiology. Surface expression was measured with (125)I-mAb 295 binding and was used to define function/nAChR. If the α4(+)/(-)β2 sites contribute equally to function, making identical β2HQT substitutions at either site should produce similar functional outcomes. Instead, highly differential outcomes within the HS isoform, and between the two isoforms, were observed. In contrast, α4VFL mutation effects were very similar in all positions of both isoforms. Our results indicate that the identity of subunits neighboring the otherwise equivalent α4(+)/(-)β2 agonist sites modifies their contributions to nAChR activation and that E-loop residues are an important contributor to this neighbor effect.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.