Endogenous neurotoxin-like protein Ly6H inhibits alpha7 nicotinic acetylcholine receptor currents at the plasma membrane

• Published in: Scientific reports 2020-07, Vol.10 (1), p.11996, Article 11996
• Main Authors: Moriwaki, Yasuhiro, Kubo, Natsuki, Watanabe, Mizuho, Asano, Shinsuke, Shinoda, Tomoki, Sugino, Taro, Ichikawa, Daiju, Tsuji, Shoutaro, Kato, Fusao, Misawa, Hidemi
• Format: Article
• Language: English
• Subjects: 631/378/2586; 631/378/340; Acetylcholine receptors (nicotinic); alpha7 Nicotinic Acetylcholine Receptor - metabolism; Alzheimer's disease; Animals; Cell lines; Cell Membrane - drug effects; Cell Membrane - metabolism; Cell membranes; Central nervous system; Channel gating; Chickens; Choline - pharmacology; HEK293 Cells; Humanities and Social Sciences; Humans; Intracellular; Ion Channel Gating - drug effects; Membrane Glycoproteins - metabolism; Membrane proteins; Membranes; Mental disorders; multidisciplinary; Mutant Proteins - metabolism; Neurodegenerative diseases; Neurotoxins; Permissive cells; Phosphoinositide Phospholipase C - metabolism; Plasma membranes; Protein Binding - drug effects; Proteins; Schizophrenia; Science; Science (multidisciplinary); Solubility; Therapeutic applications
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-68947-7

α7 nicotinic acetylcholine receptors (nAChRs) are widely expressed in the central nervous system and regarded as potential therapeutic targets for neurodegenerative conditions, such as Alzheimer’s disease and schizophrenia. Yet, despite the assumed pathophysiological importance of the α7 nAChR, molecular physiological characterization remains poorly advanced because α7 nAChR cannot be properly folded and sorted to the plasma membranes in most mammalian cell lines, thus preventing the analyses in heterologous expression system. Recently, ER-resident membrane protein NACHO was discovered as a strong chaperone for the functional expression of α7 nAChR in non-permissive cells. Ly6H, a brain-enriched GPI-anchored neurotoxin-like protein, was reported as a novel modulator regulating intracellular trafficking of α7 nAChR. In this study, we established cell lines that stably and robustly express surface α7 nAChR by introducing α7 nAChR, Ric-3, and NACHO cDNA into HEK293 cells ( T riple α 7 nAChR/ R IC-3/NACH O cells; TARO cells), and re-evaluated the function of Ly6H. We report here that Ly6H binds with α7 nAChRs on the cell membrane and modulates the channel activity without affecting intracellular trafficking of α7 nAChR.