NACHO Engages N-Glycosylation ER Chaperone Pathways for α7 Nicotinic Receptor Assembly
Summary: The α7 nicotinic acetylcholine receptor participates in diverse aspects of brain physiology and disease. Neurons tightly control α7 assembly, which relies upon NACHO, an endoplasmic reticulum (ER)-localized integral membrane protein. By constructing α7 chimeras and mutants, we find that NAC...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-08-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112472031010X |
| _version_ | 1819226538158063616 |
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| author | Hae-Jin Kweon Shenyan Gu Emily Witham Madhurima Dhara Hong Yu Elodie Desuzinges Mandon Anass Jawhari David S. Bredt |
| author_facet | Hae-Jin Kweon Shenyan Gu Emily Witham Madhurima Dhara Hong Yu Elodie Desuzinges Mandon Anass Jawhari David S. Bredt |
| author_sort | Hae-Jin Kweon |
| collection | DOAJ |
| description | Summary: The α7 nicotinic acetylcholine receptor participates in diverse aspects of brain physiology and disease. Neurons tightly control α7 assembly, which relies upon NACHO, an endoplasmic reticulum (ER)-localized integral membrane protein. By constructing α7 chimeras and mutants, we find that NACHO requires the α7 ectodomain to promote receptor assembly and surface trafficking. Also critical are two amino acids in the α7 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 α7 intracellular loop. Proteomics indicates that NACHO associates with the ER oligosaccharyltransferase machinery and with calnexin. Accordingly, NACHO-mediated effects on α7 assembly and channel function require N-glycosylation and calnexin chaperone activity. These studies identify ER pathways that mediate α7 assembly by NACHO and provide insights into novel pharmacological strategies for these crucial nicotinic receptors. |
| first_indexed | 2024-12-23T10:27:05Z |
| format | Article |
| id | doaj.art-841ce8e290134a80aef0f8d9ed38a998 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-23T10:27:05Z |
| publishDate | 2020-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-841ce8e290134a80aef0f8d9ed38a9982022-12-21T17:50:31ZengElsevierCell Reports2211-12472020-08-01326108025NACHO Engages N-Glycosylation ER Chaperone Pathways for α7 Nicotinic Receptor AssemblyHae-Jin Kweon0Shenyan Gu1Emily Witham2Madhurima Dhara3Hong Yu4Elodie Desuzinges Mandon5Anass Jawhari6David S. Bredt7Neuroscience Discovery, Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, USANeuroscience Discovery, Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, USANeuroscience Discovery, Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, USANeuroscience Discovery, Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, USANeuroscience Discovery, Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, USACALIXAR, 60 Avenue Rockefeller, 69008 Lyon, FranceCALIXAR, 60 Avenue Rockefeller, 69008 Lyon, FranceNeuroscience Discovery, Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, USA; Corresponding authorSummary: The α7 nicotinic acetylcholine receptor participates in diverse aspects of brain physiology and disease. Neurons tightly control α7 assembly, which relies upon NACHO, an endoplasmic reticulum (ER)-localized integral membrane protein. By constructing α7 chimeras and mutants, we find that NACHO requires the α7 ectodomain to promote receptor assembly and surface trafficking. Also critical are two amino acids in the α7 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 α7 intracellular loop. Proteomics indicates that NACHO associates with the ER oligosaccharyltransferase machinery and with calnexin. Accordingly, NACHO-mediated effects on α7 assembly and channel function require N-glycosylation and calnexin chaperone activity. These studies identify ER pathways that mediate α7 assembly by NACHO and provide insights into novel pharmacological strategies for these crucial nicotinic receptors.http://www.sciencedirect.com/science/article/pii/S221112472031010Xnicotinic acetylcholine receptor α7nAChRNACHOchaperoneassemblytrafficking |
| spellingShingle | Hae-Jin Kweon Shenyan Gu Emily Witham Madhurima Dhara Hong Yu Elodie Desuzinges Mandon Anass Jawhari David S. Bredt NACHO Engages N-Glycosylation ER Chaperone Pathways for α7 Nicotinic Receptor Assembly Cell Reports nicotinic acetylcholine receptor α7 nAChR NACHO chaperone assembly trafficking |
| title | NACHO Engages N-Glycosylation ER Chaperone Pathways for α7 Nicotinic Receptor Assembly |
| title_full | NACHO Engages N-Glycosylation ER Chaperone Pathways for α7 Nicotinic Receptor Assembly |
| title_fullStr | NACHO Engages N-Glycosylation ER Chaperone Pathways for α7 Nicotinic Receptor Assembly |
| title_full_unstemmed | NACHO Engages N-Glycosylation ER Chaperone Pathways for α7 Nicotinic Receptor Assembly |
| title_short | NACHO Engages N-Glycosylation ER Chaperone Pathways for α7 Nicotinic Receptor Assembly |
| title_sort | nacho engages n glycosylation er chaperone pathways for α7 nicotinic receptor assembly |
| topic | nicotinic acetylcholine receptor α7 nAChR NACHO chaperone assembly trafficking |
| url | http://www.sciencedirect.com/science/article/pii/S221112472031010X |
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