Ric-3 promotes alpha7 nicotinic receptor assembly and trafficking through the ER subcompartment of dendrites.
Ric-3 promotes alpha7 nicotinic receptor assembly and trafficking through the ER subcompartment of dendrites.
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DOI：
10.1523/jneurosci.6344-09.2010
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发表时间：
2010-07-28
期刊：
影响因子：
--
通讯作者：
Green WN
中科院分区：
文献类型：
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作者：
Alexander JK;Sagher D;Krivoshein AV;Criado M;Jefford G;Green WN
Ric-3是烟碱乙酰胆碱受体（nAChR）在C. elegans，不清楚。在这里，我们发现Ric-3可以促进或抑制由α7亚基组成的α-银环蛇毒素结合nAChR（BgtR）的细胞表面递送。在低水平下，Ric-3促进BgtR组装、内质网（ER）释放和细胞表面递送，而不从ER运输。在高Ric-3水平下，Ric-3抑制BgtR表面递送，但不抑制其组装，并且BgtR保留在ER或含Ric-3的聚集体中。在PC 12细胞中，天然BgtR从ER运输到细胞表面，在ER中观察到低水平的内源性Ric-3。在培养的神经元中，天然Ric-3水平高于PC 12细胞，并且Ric-3和α7亚基在抑制性中间神经元的胞体和树突中被发现，而不是轴突。Ric-3在快速移动的囊泡中与α7亚基一起运输到树突，在树突中它被限制在ER亚区室。我们得出结论，Ric-3有两个潜在的功能。在低水平下，Ric-3相互作用是短暂的，并促进BgtR组装和ER释放。在更高的水平，Ric-3相互作用是更长的寿命和介导的ER保留。在神经元中，Ric-3 ER保留似乎促进树突ER亚隔室内的转运，从而限制α7向树突的运输并阻止轴突转运。
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 α-Bungarotoxin-binding nAChRs (BgtRs) composed of α7 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 α7 subunits were found in somata and dendrites, but not axons, of inhibitory interneurons. Ric-3 trafficked with α7 subunits in rapidly moving vesicles to dendrites where it was restricted to the ER sub-compartment. 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 sub-compartment, thereby restricting α7 trafficking to dendrites and preventing axonal transport.