Ric-3 promotes alpha7 nicotinic receptor assembly and trafficking through the ER subcompartment of dendrites
The function of Ric-3, which is required for nicotinic acetylcholine receptor (nAChR) expression in C. elegans, is unclear. Here we found that Ric-3 can promote or inhibit cell-surface delivery of alpha-bungarotoxin-binding nAChRs (BgtRs) composed of alpha7 subunits. At low levels, Ric-3 promoted BgtR assembly, endoplasmic reticulum (ER) release, and cell-surface delivery without trafficking from the ER. At high Ric-3 levels, Ric-3 suppressed BgtR surface delivery, but not its assembly, and BgtRs were retained in the ER or in Ric-3-containing aggregates. In PC12 cells, native BgtRs trafficked to the cell surface from the ER where low levels of endogenous Ric-3 were observed. In cultured neurons, native Ric-3 levels were higher than in PC12 cells, and Ric-3 and alpha7 subunits were found in somata and dendrites, but not axons, of inhibitory interneurons. Ric-3 trafficked with alpha7 subunits in rapidly moving vesicles to dendrites, where it was restricted to the ER subcompartment. We conclude that Ric-3 has two potential functions. At low levels, Ric-3 interactions are short-lived and promote BgtR assembly and ER release. At higher levels, Ric-3 interactions are longer-lived and mediate ER retention. In neurons, Ric-3 ER retention appears to promote transport within the dendritic ER subcompartment, thereby restricting alpha7 trafficking to dendrites and preventing axonal transport.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2010 |
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| Erschienen: |
2010 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:30 |
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| Enthalten in: |
The Journal of neuroscience : the official journal of the Society for Neuroscience - 30(2010), 30 vom: 28. Juli, Seite 10112-26 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Alexander, John K [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 20.08.2010 Date Revised 09.03.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.1523/JNEUROSCI.6344-09.2010 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM199924856 |
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| 100 | 1 | |a Alexander, John K |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Ric-3 promotes alpha7 nicotinic receptor assembly and trafficking through the ER subcompartment of dendrites |
| 264 | 1 | |c 2010 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 20.08.2010 | ||
| 500 | |a Date Revised 09.03.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The function of Ric-3, which is required for nicotinic acetylcholine receptor (nAChR) expression in C. elegans, is unclear. Here we found that Ric-3 can promote or inhibit cell-surface delivery of alpha-bungarotoxin-binding nAChRs (BgtRs) composed of alpha7 subunits. At low levels, Ric-3 promoted BgtR assembly, endoplasmic reticulum (ER) release, and cell-surface delivery without trafficking from the ER. At high Ric-3 levels, Ric-3 suppressed BgtR surface delivery, but not its assembly, and BgtRs were retained in the ER or in Ric-3-containing aggregates. In PC12 cells, native BgtRs trafficked to the cell surface from the ER where low levels of endogenous Ric-3 were observed. In cultured neurons, native Ric-3 levels were higher than in PC12 cells, and Ric-3 and alpha7 subunits were found in somata and dendrites, but not axons, of inhibitory interneurons. Ric-3 trafficked with alpha7 subunits in rapidly moving vesicles to dendrites, where it was restricted to the ER subcompartment. We conclude that Ric-3 has two potential functions. At low levels, Ric-3 interactions are short-lived and promote BgtR assembly and ER release. At higher levels, Ric-3 interactions are longer-lived and mediate ER retention. In neurons, Ric-3 ER retention appears to promote transport within the dendritic ER subcompartment, thereby restricting alpha7 trafficking to dendrites and preventing axonal transport | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Autoantigens |2 NLM | |
| 650 | 7 | |a Bungarotoxins |2 NLM | |
| 650 | 7 | |a Cholinergic Agents |2 NLM | |
| 650 | 7 | |a Chrna7 protein, human |2 NLM | |
| 650 | 7 | |a Chrna7 protein, mouse |2 NLM | |
| 650 | 7 | |a Chrna7 protein, rat |2 NLM | |
| 650 | 7 | |a Cyan Fluorescent Protein |2 NLM | |
| 650 | 7 | |a Golgin subfamily A member 2 |2 NLM | |
| 650 | 7 | |a Iodine Isotopes |2 NLM | |
| 650 | 7 | |a Membrane Proteins |2 NLM | |
| 650 | 7 | |a Molecular Chaperones |2 NLM | |
| 650 | 7 | |a Receptors, Nicotinic |2 NLM | |
| 650 | 7 | |a Ric-3 protein, mouse |2 NLM | |
| 650 | 7 | |a alpha7 Nicotinic Acetylcholine Receptor |2 NLM | |
| 650 | 7 | |a Green Fluorescent Proteins |2 NLM | |
| 650 | 7 | |a 147336-22-9 |2 NLM | |
| 650 | 7 | |a Glutamate Decarboxylase |2 NLM | |
| 650 | 7 | |a EC 4.1.1.15 |2 NLM | |
| 650 | 7 | |a Protein Disulfide-Isomerases |2 NLM | |
| 650 | 7 | |a EC 5.3.4.1 |2 NLM | |
| 650 | 7 | |a Acetylcholine |2 NLM | |
| 650 | 7 | |a N9YNS0M02X |2 NLM | |
| 700 | 1 | |a Sagher, Daphna |e verfasserin |4 aut | |
| 700 | 1 | |a Krivoshein, Arcadius V |e verfasserin |4 aut | |
| 700 | 1 | |a Criado, Manuel |e verfasserin |4 aut | |
| 700 | 1 | |a Jefford, Gregory |e verfasserin |4 aut | |
| 700 | 1 | |a Green, William N |e verfasserin |4 aut | |
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| 856 | 4 | 0 | |u http://dx.doi.org/10.1523/JNEUROSCI.6344-09.2010 |3 Volltext |
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