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The fifth subunit in α3β4 nicotinic receptor is more than an accessory subunit
Author(s) -
Crespi Arianna,
Plutino Simona,
Sciaccaluga Miriam,
Righi Marco,
Borgese Nica,
Fucile Sergio,
Gotti Cecilia,
Colombo Sara Francesca
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201701377r
Subject(s) - protein subunit , gamma aminobutyric acid receptor subunit alpha 1 , interleukin 10 receptor, alpha subunit , nicotinic acetylcholine receptor , chemistry , receptor , nicotinic agonist , biology , biochemistry , g alpha subunit , gene
The α3ß4 subtype is the predominant neuronal nicotinic acetylcholine receptor present in the sensory and autonomic ganglia and in a subpopulation of brain neurons. This subtype can form pentameric receptors with either 2 or 3 ß4 subunits that have different pharmacologic and functional properties. To further investigate the role of the fifth subunit, we coexpressed a dimeric construct coding for a single polypeptide containing the ß4and α3 subunit sequences, with different monomeric subunits. With this strategy, which allowed the formation of single populations of receptors with unique stoichiometry, we demonstrated with immunofluorescence and biochemical and functional assays that only the receptors with 3 ß4 subunits are efficiently expressed at the plasma membrane. Moreover, the LFM export motif of ß4 subunit in the fifth position exerts a unique function in the regulation of the intracellular trafficking of the receptors, their exposure at the cell surface, and consequently, their function, whereas the same export motif present in the ß4 subunits forming the acetylcholine binding site is dispensable.—Crespi, A., Plutino, S., Sciaccaluga, M., Righi, M., Borgese, N., Fucile, S., Gotti, C., Colombo, S. F. The fifth subunit in α3ß4 nicotinic receptor is more than an accessory subunit. FASEB J . 32, 4190–4202 (2018). www.fasebj.org