| First Author | Kweon HJ | Year | 2020 |
| Journal | Cell Rep | Volume | 32 |
| Issue | 6 | Pages | 108025 |
| PubMed ID | 32783947 | Mgi Jnum | J:304156 |
| Mgi Id | MGI:6694364 | Doi | 10.1016/j.celrep.2020.108025 |
| Citation | Kweon HJ, et al. (2020) NACHO Engages N-Glycosylation ER Chaperone Pathways for alpha7 Nicotinic Receptor Assembly. Cell Rep 32(6):108025 |
| abstractText | The alpha7 nicotinic acetylcholine receptor participates in diverse aspects of brain physiology and disease. Neurons tightly control alpha7 assembly, which relies upon NACHO, an endoplasmic reticulum (ER)-localized integral membrane protein. By constructing alpha7 chimeras and mutants, we find that NACHO requires the alpha7 ectodomain to promote receptor assembly and surface trafficking. Also critical are two amino acids in the alpha7 second transmembrane domain. NACHO-mediated assembly is independent and separable from that induced by cholinergic ligands or RIC-3 protein, the latter of which acts on the large alpha7 intracellular loop. Proteomics indicates that NACHO associates with the ER oligosaccharyltransferase machinery and with calnexin. Accordingly, NACHO-mediated effects on alpha7 assembly and channel function require N-glycosylation and calnexin chaperone activity. These studies identify ER pathways that mediate alpha7 assembly by NACHO and provide insights into novel pharmacological strategies for these crucial nicotinic receptors. |
