The fifth subunit in α3β4 nicotinic receptor is more than an accessory subunit

What is it about?

Heteromeric neuronal nicotinic acetylcholine receptors (nAChRs) are pentameric cation channels with two orthosteric ACh- nicotine-binding sites formed at the interface between an α and a β subunit in two αβsubunit pairs and a fifth subunit, termed "accessory subunit", that does not directly participate in forming the binding site. We were interested in studying the α3β4 nicotinic receptor, a subtype that is rare in brain but predominant in the autonomic nervous system, and whose mRNA is expressed also in non-neuronal cells like in lung carcinoma cells. This subtype has an important role in nicotine addiction and the expression of this receptor has been involved in the risk of nicotine dependence, smoking and lung cancer. In order to exert their functions these receptors synthesised in the endoplasmic reticulum must be localised at the cell surface. In this work we developed a strategy to express single receptor types with a defined accessory subunit in heterologous cells. Our results highlight that the so-called accessory subunit indeed exerts a unique function in the regulation of the intracellular trafficking of the receptors, of their exposure at the cell surface and consequently of their physiological functional activity.

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