NACHO and 14-3-3 promote expression of distinct subunit stoichiometries of the α4β2 acetylcholine receptor
| Autor: | Sara T. Whiteman, Steven M. Sine, Simone Mazzaferro, Arthur Beyder, Constanza Alcaino |
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| Rok vydání: | 2020 |
| Předmět: |
Patch-Clamp Techniques
Protein subunit Allosteric regulation Receptors Nicotinic Ligands Article 03 medical and health sciences Cellular and Molecular Neuroscience Animals Humans Nicotinic Agonists Receptor Molecular Biology Ion channel Acetylcholine receptor Neurons Pharmacology Oxadiazoles 0303 health sciences Chemistry 030302 biochemistry & molecular biology Cell Biology Acetylcholine Cell biology Protein Subunits Nicotinic agonist 14-3-3 Proteins Molecular Medicine Ligand-gated ion channel Heterologous expression |
| Zdroj: | Cell Mol Life Sci |
| ISSN: | 1420-9071 1420-682X |
| Popis: | Nicotinic acetylcholine receptors (nAChRs) belong to the superfamily of pentameric ligand-gated ion channels, and in neuronal tissues, are assembled from various types of α- and β-subunits. Furthermore, the subunits α4 and β2 assemble in two predominant stoichiometric forms, (α4)(2)(β2)(3) and (α4)(3)(β2)(2), forming receptors with dramatically different sensitivity to agonists and allosteric modulators. However, mechanisms by which the two stoichiometric forms are regulated are not known. Here, using heterologous expression in mammalian cells, single-channel patch clamp electrophysiology, and calcium imaging, we show that the ER resident protein NACHO selectively promotes expression of the (α4)(2)(β2)(3) stoichiometry, whereas the cytosolic molecular chaperone 14-3-3η selectively promotes expression of the (α4)(3)(β2)(2) stoichiometry. Thus, NACHO and 14-3-3η are potential physiological regulators of subunit stoichiometry, and are potential drug targets for re-balancing the stoichiometry in pathological conditions involving α4β2 nAChRs such as nicotine dependence and epilepsy. |
| Databáze: | OpenAIRE |
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