Novel acetylcholine receptor chaperone

Definition:

Molecular chaperone which mediates the proper assembly and functional expression of the nicotinic acetylcholine receptors (nAChRs) throughout the brain. Essential for the proper folding, assembly, function and surface trafficking of alpha-7 (CHRNA7), alpha-4-beta-2, alpha-3-beta-2 and alpha-3-beta-4 receptors. Stably associates with ribophorin-1 (RPN1) and ribophorin-2 (RPN2) (components of the oligosaccharyl transferase (OST) complex) and with calnexin (CANX), both of which are critical for NACHO-mediated effects on CHRNA7 assembly and function (By similarity). Facilitates the proper folding and assembly of alpha-6-beta-2 and alpha-6-beta-2-beta-3 receptors and acts at early stages of the nAChRs subunit assembly. Promotes the expression of the alpha-4(2):beta-2(3) stoichiometric form over the alpha-4(3):beta-2(2) form.

References:

[1]. Shenyan Gu, et al. Brain α7 Nicotinic Acetylcholine Receptor Assembly Requires NACHO. Neuron. 2016 Mar 2;89(5):948-55. [Content Brief]

[2]. Jose A Matta, et al. NACHO Mediates Nicotinic Acetylcholine Receptor Function throughout the Brain. Cell Rep. 2017 Apr 25;19(4):688-696. [Content Brief]

[3]. Hae-Jin Kweon, et al. NACHO Engages N-Glycosylation ER Chaperone Pathways for α7 Nicotinic Receptor Assembly. Cell Rep. 2020 Aug 11;32(6):108025. [Content Brief]

[4]. Elizabeth B Rex, et al. A Genome-Wide Arrayed cDNA Screen to Identify Functional Modulators of α7 Nicotinic Acetylcholine Receptors. SLAS Discov. 2017 Feb;22(2):155-165. [Content Brief]

[5]. Anish Deshpande, et al. Why Does Knocking Out NACHO, But Not RIC3, Completely Block Expression of α7 Nicotinic Receptors in Mouse Brain?. Biomolecules. 2020 Mar 19;10(3):470. [Content Brief]

[6]. Simone Mazzaferro, et al. NACHO and 14-3-3 promote expression of distinct subunit stoichiometries of the α4β2 acetylcholine receptor. Cell Mol Life Sci. 2021 Feb;78(4):1565-1575. [Content Brief]

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