دورية أكاديمية
أعرض في EDS

Rare Missense Variants of the Human β4 Subunit Alter Nicotinic α3β4 Receptor Plasma Membrane Localisation.

التفاصيل البيبلوغرافية
العنوان: Rare Missense Variants of the Human β4 Subunit Alter Nicotinic α3β4 Receptor Plasma Membrane Localisation.
المؤلفون: Colombo SF; CNR Institute of Neuroscience, 20854 Vedano al Lambro, Italy.; NeuroMi Milan Center for Neuroscience, University of Milano-Bicocca, 20126 Milan, Italy., Galli C; CNR Institute of Neuroscience, 20854 Vedano al Lambro, Italy.; NeuroMi Milan Center for Neuroscience, University of Milano-Bicocca, 20126 Milan, Italy., Crespi A; CNR Institute of Neuroscience, 20854 Vedano al Lambro, Italy.; NeuroMi Milan Center for Neuroscience, University of Milano-Bicocca, 20126 Milan, Italy., Renzi M; Department of Physiology and Pharmacology, 'Sapienza' University of Rome, 00185 Rome, Italy., Gotti C; CNR Institute of Neuroscience, 20854 Vedano al Lambro, Italy.; NeuroMi Milan Center for Neuroscience, University of Milano-Bicocca, 20126 Milan, Italy.
المصدر: Molecules (Basel, Switzerland) [Molecules] 2023 Jan 27; Vol. 28 (3). Date of Electronic Publication: 2023 Jan 27.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, c1995-
مواضيع طبية MeSH: Mutation, Missense* , Receptors, Nicotinic*/metabolism, Humans ; Ligands ; Nicotine/metabolism ; Cell Membrane/metabolism
مستخلص: α3β4 nicotinic acetylcholine receptors (nARs) are pentameric ligand-gated cation channels that function in peripheral tissue and in the peripheral and central nervous systems, where they are critical mediators of ganglionic synaptic transmission and modulators of reward-related behaviours. In the pentamer, two α3β4 subunit couples provide ligand-binding sites, and the fifth single (accessory) subunit (α3 or β4) regulates receptor trafficking from the endoplasmic reticulum to the cell surface. A number of rare missense variants of the human β4 subunit have recently been linked to nicotine dependence and/or sporadic amyotrophic lateral sclerosis, and altered responses to nicotine have been reported for these variants; however, it is unknown whether the effects of mutations depend on the subunit within the ligand-binding couples and/or on the fifth subunit. Here, by expressing single populations of pentameric receptors with fixed stoichiometry in cultured cells, we investigated the effect of β4 variants in the fifth position on the assembly and surface exposure of α3β4 nAChRs. The results demonstrate that the missense mutations in the accessory subunit alone, despite not affecting the assembly of α3β4 receptors, alter their trafficking and surface localisation. Thus, altered trafficking of an otherwise functional nAChR may underlie the pathogenic effects of these mutations.
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معلومات مُعتمدة: 2016 Fondazione Monzino, Milano, Italy
فهرسة مساهمة: Keywords: SNPs; nAChRs; stoichiometry; α3β4 nicotinic subtype; α3β4 trafficking
المشرفين على المادة: 0 (Ligands)
0 (Receptors, Nicotinic)
6M3C89ZY6R (Nicotine)
تواريخ الأحداث: Date Created: 20230211 Date Completed: 20230214 Latest Revision: 20230214
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC9919425
DOI: 10.3390/molecules28031247
PMID: 36770914
قاعدة البيانات: MEDLINE
الوصف
تدمد:1420-3049
DOI:10.3390/molecules28031247