NACHO Mediates Nicotinic Acetylcholine Receptor Function throughout the Brain - PubMed (original) (raw)
NACHO Mediates Nicotinic Acetylcholine Receptor Function throughout the Brain
Jose A Matta et al. Cell Rep. 2017.
Free article
Abstract
Neuronal nicotinic acetylcholine receptors (nAChRs) participate in diverse aspects of brain function and mediate behavioral and addictive properties of nicotine. Neuronal nAChRs derive from combinations of α and β subunits, whose assembly is tightly regulated. NACHO was recently identified as a chaperone for α7-type nAChRs. Here, we find NACHO mediates assembly of all major classes of presynaptic and postsynaptic nAChR tested. NACHO acts at early intracellular stages of nAChR subunit assembly and then synergizes with RIC-3 for receptor surface expression. NACHO knockout mice show profound deficits in binding sites for α-bungarotoxin, epibatidine, and conotoxin MII, illustrating essential roles for NACHO in proper assembly of α7-, α4β2-, and α6-containing nAChRs, respectively. By contrast, GABAA receptors are unaffected consistent with NACHO specifically modulating nAChRs. NACHO knockout mice show abnormalities in locomotor and cognitive behaviors compatible with nAChR deficiency and underscore the importance of this chaperone for physiology and disease associated with nAChRs.
Keywords: Alzheimer’s; NACHO; RIC3; acetylcholine; chaperone; learning; nicotine; receptor; synapse.
Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Similar articles
- Genetic deletion of the adenosine A(2A) receptor prevents nicotine-induced upregulation of α7, but not α4β2* nicotinic acetylcholine receptor binding in the brain.
Metaxas A, Al-Hasani R, Farshim P, Tubby K, Berwick A, Ledent C, Hourani S, Kitchen I, Bailey A. Metaxas A, et al. Neuropharmacology. 2013 Aug;71:228-36. doi: 10.1016/j.neuropharm.2013.03.023. Epub 2013 Apr 11. Neuropharmacology. 2013. PMID: 23583933 - Brain α7 Nicotinic Acetylcholine Receptor Assembly Requires NACHO.
Gu S, Matta JA, Lord B, Harrington AW, Sutton SW, Davini WB, Bredt DS. Gu S, et al. Neuron. 2016 Mar 2;89(5):948-55. doi: 10.1016/j.neuron.2016.01.018. Epub 2016 Feb 11. Neuron. 2016. PMID: 26875622 - High-affinity epibatidine binding of functional, human alpha7-nicotinic acetylcholine receptors stably and heterologously expressed de novo in human SH-EP1 cells.
Peng JH, Fryer JD, Hurst RS, Schroeder KM, George AA, Morrissy S, Groppi VE, Leonard SS, Lukas RJ. Peng JH, et al. J Pharmacol Exp Ther. 2005 Apr;313(1):24-35. doi: 10.1124/jpet.104.079004. Epub 2004 Dec 8. J Pharmacol Exp Ther. 2005. PMID: 15590768 - The subtypes of nicotinic acetylcholine receptors on dopaminergic terminals of mouse striatum.
Grady SR, Salminen O, Laverty DC, Whiteaker P, McIntosh JM, Collins AC, Marks MJ. Grady SR, et al. Biochem Pharmacol. 2007 Oct 15;74(8):1235-46. doi: 10.1016/j.bcp.2007.07.032. Epub 2007 Jul 27. Biochem Pharmacol. 2007. PMID: 17825262 Free PMC article. Review. - Speculation on How RIC-3 and Other Chaperones Facilitate α7 Nicotinic Receptor Folding and Assembly.
Loring RH. Loring RH. Molecules. 2022 Jul 15;27(14):4527. doi: 10.3390/molecules27144527. Molecules. 2022. PMID: 35889400 Free PMC article. Review.
Cited by
- Nicotinic α7 acetylcholine receptor (α7nAChR) in human airway smooth muscle.
Borkar NA, Roos B, Prakash YS, Sathish V, Pabelick CM. Borkar NA, et al. Arch Biochem Biophys. 2021 Jul 30;706:108897. doi: 10.1016/j.abb.2021.108897. Epub 2021 May 15. Arch Biochem Biophys. 2021. PMID: 34004182 Free PMC article. - Serine residues in the α4 nicotinic acetylcholine receptor subunit regulate surface α4β2* receptor expression and clustering.
Zambrano CA, Escobar D, Ramos-Santiago T, Bollinger I, Stitzel J. Zambrano CA, et al. Biochem Pharmacol. 2019 Jan;159:64-73. doi: 10.1016/j.bcp.2018.11.008. Epub 2018 Nov 9. Biochem Pharmacol. 2019. PMID: 30414940 Free PMC article. - Novel Cell-Based Assay for Alpha-3 Nicotinic Receptor Antibodies Detects Antibodies Exclusively in Autoimmune Autonomic Ganglionopathy.
Karagiorgou K, Dandoulaki M, Mantegazza R, Andreetta F, Furlan R, Lindstrom J, Zisimopoulou P, Chroni E, Kokotis P, Anagnostou E, Tzanetakos D, Breza M, Katsarou Z, Amoiridis G, Mastorodemos V, Bregianni M, Bonakis A, Tsivgoulis G, Voumvourakis K, Tzartos S, Tzartos J. Karagiorgou K, et al. Neurol Neuroimmunol Neuroinflamm. 2022 Mar 29;9(3):e1162. doi: 10.1212/NXI.0000000000001162. Print 2022 May. Neurol Neuroimmunol Neuroinflamm. 2022. PMID: 35351814 Free PMC article. - NACHO and 14-3-3 promote expression of distinct subunit stoichiometries of the α4β2 acetylcholine receptor.
Mazzaferro S, Whiteman ST, Alcaino C, Beyder A, Sine SM. Mazzaferro S, et al. Cell Mol Life Sci. 2021 Feb;78(4):1565-1575. doi: 10.1007/s00018-020-03592-x. Epub 2020 Jul 16. Cell Mol Life Sci. 2021. PMID: 32676916 Free PMC article. - CHRFAM7A: A human specific fusion gene, accounts for the translational gap for cholinergic strategies in Alzheimer's disease.
Szigeti K, Ihnatovych I, Birkaya B, Chen Z, Ouf A, Indurthi DC, Bard JE, Kann J, Adams A, Chaves L, Sule N, Reisch JS, Pavlik V, Benedict RHB, Auerbach A, Wilding G. Szigeti K, et al. EBioMedicine. 2020 Sep;59:102892. doi: 10.1016/j.ebiom.2020.102892. Epub 2020 Aug 17. EBioMedicine. 2020. PMID: 32818803 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases