NACHO and 14-3-3 promote expression of distinct subunit stoichiometries of the α4ß2 acetylcholine receptor.
Cell Mol Life Sci
; 78(4): 1565-1575, 2021 Feb.
Article
em En
| MEDLINE
| ID: mdl-32676916
ABSTRACT
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 ß-subunits. Furthermore, the subunits α4 and ß2 assemble in two predominant stoichiometric forms, (α4)2(ß2)3 and (α4)3(ß2)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 the expression of the (α4)2(ß2)3 stoichiometry, whereas the cytosolic molecular chaperone 14-3-3η selectively promotes the expression of the (α4)3(ß2)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 α4ß2 nAChRs such as nicotine dependence and epilepsy.
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Base de dados:
MEDLINE
Assunto principal:
Receptores Nicotínicos
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Subunidades Proteicas
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Proteínas 14-3-3
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Neurônios
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article