AI Article Synopsis
- Ric-3 plays a dual role in the trafficking of alpha7 nAChRs, promoting their assembly and delivery to the cell membrane at low levels, while inhibiting their surface delivery at high levels by retaining them in the endoplasmic reticulum (ER).
- In PC12 cells, low levels of endogenous Ric-3 allow BgtR trafficking to the cell surface, whereas in cultured neurons, higher Ric-3 levels are associated with specific localization in somata and dendrites.
- The findings suggest that Ric-3's function may involve facilitating the transport of nAChRs within dendrites while preventing their movement into axons, indicating a complex regulatory mechanism in neuronal environments.
Article Abstract
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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945888 | PMC |
| http://dx.doi.org/10.1523/JNEUROSCI.6344-09.2010 | DOI Listing |
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