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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
Neurochemistry international ( IF 4.2 ) Pub Date : 2017-10-12 , DOI: 10.1016/j.neuint.2017.10.007
Haibo Bao , Xixia Xu , Wei Liu , Na Yu , Zewen Liu

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 α7 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 Locα1/rβ2 expressed in Xenopus oocytes. As a representative, the co-expression of RIC-3v4 exhibited the decreased agonist responses (Imax) on oocytes, lower specific [3H]epibatidine binding (Bmax) on plasma membrane protein (PMP), and reduced subunit levels in PMP, which showed that the mature Locα1/rβ2 on the plasma membrane was decreased by the co-expression of RIC-3. In contrast, the [3H]epibatidine binding and mature Locα1/rβ2 levels in the endoplasmic reticulum membrane protein (ERMP) were much increased when co-expressing with RIC-3v4. The [3H]epibatidine binding and mature Locα1/rβ2 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 Locα1/rβ2 receptor levels on ER of Xenopus oocytes, but these mature receptors were mostly kept on ER and suppressed to transport to plasma membrane.



中文翻译:

昆虫nAChR伴侣RIC-3对杂种受体的双重影响:促进内质网的装配,但抑制爪蟾卵母细胞向质膜的转运。

对胆碱酯酶(RIC)-3抑制剂的抗性促进了作为分子伴侣的神经元烟碱型乙酰胆碱受体(nAChRs)的成熟(折叠和组装)。RIC-3对同型α7nAChRs的调节作用始终是积极的,但在报道中其对异聚体亚型的作用却不一致。在这项研究中,从东方蝗中鉴定出五种RIC-3同工型。四种同工型对非洲爪蟾卵母细胞中表达的杂合受体Locα1/rβ2具有明显的作用。作为代表,RIC-3v4的共表达在卵母细胞上显示出降低的激动剂反应(I max),较低的特异性[ 3 H] epibatidine结合(B max)和质膜蛋白(PMP)中亚基水平的降低,表明RIC-3的共表达降低了质膜上成熟Locα1/rβ2的表达。相反,当与RIC-3v4共表达时,内质网膜蛋白(ERMP)中的[ 3 H] epibatidine结合和成熟Locα1/rβ2水平大大增加。总膜蛋白(TMP)中的[ 3 H] epibatidine结合和成熟的Locα1/rβ2水平产生了与ERMP中相似的结果。综上所述,结果表明RIC-3的共表达增加了非洲爪蟾卵母细胞ER上成熟的Locα1/rβ2受体水平,但这些成熟受体大部分保留在ER上并被抑制转运至质膜。

更新日期:2017-10-12
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