Dual effects of insect nAChR chaperone RIC-3 on hybrid receptor: Promoting assembly on endoplasmic reticulum but suppressing transport to plasma membrane on Xenopus oocytes
Dual effects of insect nAChR chaperone RIC-3 on hybrid receptor: Promoting assembly on endoplasmic reticulum but suppressing transport to plasma membrane on Xenopus oocytes
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昆虫 nAChR 伴侣 RIC-3 对杂合受体的双重作用：促进内质网组装但抑制非洲爪蟾卵母细胞向质膜的运输
DOI：
10.1016/j.neuint.2017.10.007
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发表时间：
2018-05-01
影响因子：
4.2
通讯作者：
Liu, Zewen
中科院分区：
文献类型：
--
作者：
Bao, Haibo;Xu, Xixia;Liu, Zewen
对胆碱酯酶抑制剂 (RIC) -3 的抗性促进作为分子伴侣的神经元烟碱乙酰胆碱受体 (nAChR) 的成熟（折叠和组装）。 RIC-3对同聚α7 nAChR的调节作用始终是正向的，但其对异聚亚型的作用在报道中不一致。在这项研究中，从飞蝗中鉴定出了五种 RIC-3 亚型。四种亚型对非洲爪蟾卵母细胞中表达的杂种受体 Loc α 1/r β 2 表现出明显的影响。作为代表，RIC-3v4的共表达表现出卵母细胞上的激动剂反应（I-max）降低、质膜蛋白（PMP）上的特异性[H-3]epibatidine结合（B-max）降低以及PMP中的亚基水平降低，这表明质膜上的成熟Loc α1/rβ2因RIC-3的共表达而减少。相反，当与RIC-3v4共表达时，内质网膜蛋白(ERMP)中的[H-3]epibatidine结合和成熟Loc α 1/r β 2水平大大增加。总膜蛋白 (TMP) 中的 [H-3]epibatidine 结合和成熟 Loc α 1/r β 2 水平给出了与 ERMP 中相似的结果。综合数据，结果表明，RIC-3的共表达增加了非洲爪蟾卵母细胞ER上成熟Locα1/rβ2受体的水平，但这些成熟受体大多保留在ER上并抑制向质膜的转运。 (C) 2017 Elsevier Ltd. 保留所有权利。
Resistance to inhibitors of cholinesterase (RIC) -3 promotes the maturation (folding and assembly) of neuronal nicotinic acetylcholine receptors (nAChRs) as a molecular chaperone. The modulation effects of RIC-3 on homomeric alpha 7 nAChRs are always positive, but its effects on heteromeric subtypes are inconsistent among reports. In this study, five RIC-3 isoforms were identified from Locusta migratoria. Four isoforms showed obvious effects on hybrid receptor Loc alpha 1/r beta 2 expressed in Xenopus oocytes. As a representative, the co-expression of RIC-3v4 exhibited the decreased agonist responses (I-max) on oocytes, lower specific [H-3]epibatidine binding (B-max) on plasma membrane protein (PMP), and reduced subunit levels in PMP, which showed that the mature Loc alpha 1/r beta 2 on the plasma membrane was decreased by the co-expression of RIC-3. In contrast, the [H-3]epibatidine binding and mature Loc alpha 1/r beta 2 levels in the endoplasmic reticulum membrane protein (ERMP) were much increased when co-expressing with RIC-3v4. The [H-3]epibatidine binding and mature Loc alpha 1/r beta 2 levels in total membrane protein (TMP) gave the similar results as that in ERMP. Taking data together, the results showed that the co-expression of RIC-3 increased the mature Loc alpha 1/r beta 2 receptor levels on ER of Xenopus oocytes, but these mature receptors were mostly kept on ER and suppressed to transport to plasma membrane. (C) 2017 Elsevier Ltd. All rights reserved.