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8.A.179.  The Novel Acetylcholine Receptor Chaperone (NACHO) Family

NACHO (TMEM35A) is a molecular chaperone that mediates the proper assembly and functional expression of nicotinic acetylcholine receptors (nAChRs) throughout the brain (Gu et al. 2016, Rex et al. 2017, Kweon et al. 2020). It is 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 (Gu et al. 2016, , Matta et al. 2017, Deshpande et al. 2020, Kweon et al. 2020). It  stably associates with ribophorin-1 (RPN1) and ribophorin-2 (RPN2) (components of the oligosaccharyl transferase (OST) complex; TC# 9.B.142.3.17) and with calnexin (CANX; TC# 8.A.165), all of which are critical for NACHO-mediated effects on CHRNA7 assembly and function. NACHO 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 (Matta et al. 2017). It promotes the expression of the alpha-42:beta-23 stoichiometric form over the alpha-43:beta-22 form (Mazzaferro et al. 2021).




References associated with 8.A.179 family:

Deshpande, A., R.M. Vinayakamoorthy, B.K. Garg, J.P. Thummapudi, G. Oza, K. Adhikari, A. Agarwal, P. Dalvi, S. Iyer, S. Thulasi Raman, V. Ramesh, A. Rameshbabu, A. Rezvaya, S. Sukumaran, S. Swaminathan, B. Tilak, Z. Wang, P.V. Tran, and R.H. Loring. (2020). Why Does Knocking Out NACHO, But Not RIC3, Completely Block Expression of α7 Nicotinic Receptors in Mouse Brain? Biomolecules 10:. 32204458
Gu, S., J.A. Matta, B. Lord, A.W. Harrington, S.W. Sutton, W.B. Davini, and D.S. Bredt. (2016). Brain α7 Nicotinic Acetylcholine Receptor Assembly Requires NACHO. Neuron. 89: 948-955. 26875622
Hoffman, J.L., S. Faccidomo, B.L. Saunders, S.M. Taylor, M. Kim, and C.W. Hodge. (2021). Inhibition of AMPA receptors (AMPARs) containing transmembrane AMPAR regulatory protein γ-8 with JNJ-55511118 shows preclinical efficacy in reducing chronic repetitive alcohol self-administration. Alcohol Clin Exp Res 45: 1424-1435. 34086361
Kweon, H.J., S. Gu, E. Witham, M. Dhara, H. Yu, E.D. Mandon, A. Jawhari, and D.S. Bredt. (2020). NACHO Engages N-Glycosylation ER Chaperone Pathways for α7 Nicotinic Receptor Assembly. Cell Rep 32: 108025. 32783947
Ma, X., M. Li, G. Lu, R. Wang, Y. Wei, Y. Guo, Y. Yu, and C. Jiang. (2021). Anti-inflammation of epicatechin mediated by TMEM35A and TMPO in bovine mammary epithelial cell line cells and mouse mammary gland. J Dairy Sci 104: 12925-12938. 34593235
Matta, J.A., S. Gu, W.B. Davini, B. Lord, E.R. Siuda, A.W. Harrington, and D.S. Bredt. (2017). NACHO Mediates Nicotinic Acetylcholine Receptor Function throughout the Brain. Cell Rep 19: 688-696. 28445721
Mazzaferro, S., S.T. Whiteman, C. Alcaino, A. Beyder, and S.M. Sine. (2021). NACHO and 14-3-3 promote expression of distinct subunit stoichiometries of the α4β2 acetylcholine receptor. Cell Mol Life Sci 78: 1565-1575. 32676916
Rex, E.B., N. Shukla, S. Gu, D. Bredt, and D. DiSepio. (2017). A Genome-Wide Arrayed cDNA Screen to Identify Functional Modulators of α7 Nicotinic Acetylcholine Receptors. SLAS Discov 22: 155-165. 27789755