ArticleNeuropharmacology2014
A signal peptide missense mutation associated with nicotine dependence alters α2*-nicotinic acetylcholine receptor function.
Article in Neuropharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 19 citations in OpenAlex.
- Shared genetic architecture of psychoactive substance use and pan-cancer: insights from a large‑scale genome‑wide cross‑trait analysis.BMC medicine · 2026Article
- Probing effects of the SARS-CoV-2 E protein on membrane curvature and intracellular calcium.Biochimica et biophysica acta. Biomembranes · 2022Article
- Structural Insights into the Role of β3 nAChR Subunit in the Activation of Nicotinic Receptors.Molecules (Basel, Switzerland) · 2022Article
- Nicotinic Acetylcholine Receptors of PC12 Cells.Cellular and molecular neurobiology · 2021Review
- Involvement of Interferon Regulatory Factor 7 in Nicotine's Suppression of Antiviral Immune Responses.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2019Article
- Maternal overnutrition programs hedonic and metabolic phenotypes across generations through sperm tsRNAs.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Understanding structure-function relationships of the human neuronal acetylcholine receptor: insights from the first crystal structures of neuronal subunits.British journal of pharmacology · 2018Review
- Cholinergic receptor nicotinic alpha 5 subunit polymorphisms are associated with smoking cessation success in women.BMC medical genetics · 2018Article
- Insights Into Nicotinic Receptor Signaling in Nicotine Addiction: Implications for Prevention and Treatment.Current neuropharmacology · 2018Review
- Associations of rare nicotinic cholinergic receptor gene variants to nicotine and alcohol dependence.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2016Article
- Crystal structure of a human neuronal nAChR extracellular domain in pentameric assembly: Ligand-bound α2 homopentamer.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Converging findings from linkage and association analyses on susceptibility genes for smoking and other addictions.Molecular psychiatry · 2016Review
- Article
- Nicotine withdrawal.Current topics in behavioral neurosciences · 2015Review
- Two rare variations, D478N and D478E, that occur at the same amino acid residue in nicotinic acetylcholine receptor (nAChR) α2 subunit influence nAChR function.Neuropharmacology · 2014Article
- Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
A cytosine to thymidine (C → T) missense mutation in the signal peptide (SP) sequence (rs2472553) of the nicotinic acetylcholine receptor (nAChR) α2 subunit produces a threonine-to-isoleucine substitution (T22I) often associated with nicotine dependence (ND). We assessed effects on function of α2*-nAChR ('*'indicates presence of additional subunits) of this mutation, which could alter SP cleavage, RNA/protein secondary structure, and/or efficiency of transcription, translation, subunit assembly, receptor trafficking or cell surface expression. Two-electrode voltage clamp analyses indicate peak current responses to ACh or nicotine are decreased 2.8-5.8-fold for putative low sensitivity (LS; 10:1 ratio of α:β subunit cRNAs injected) α2β2- or α2β4-nAChR and increased for putative high sensitivity (HS; 1:10 α:β subunit ratio) α2β2- (5.7-15-fold) or α2β4- (1.9-2.2-fold) nAChR as a result of the mutation. Agonist potencies are decreased 1.6-4-fold for putative LS or HS α2(T22I)β2-nAChR or for either α2*-nAChR subtype formed in the presence of equal amounts of subunit cRNA, slightly decreased for LS α2(T22I)β4-nAChR, but increased 1.4-2.4-fold for HS α2(T22I)β4-nAChR relative to receptors containing wild-type α2 subunits. These effects suggest that the α2 subunit SP mutation generally favors formation of LS receptor isoforms. We hypothesize that lower sensitivity of human α2*-nAChR to nicotine could contribute to increased susceptibility to ND. To our knowledge this is the first report of a SP mutation having a functional effect in a member of cys-loop family of ligand-gated ion channels.
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