Quantitative analysis on secretion level of CDNF regulated by two key alpha-helices in CDNF protein
Quantitative analysis on secretion level of CDNF regulated by two key alpha-helices in CDNF protein
复制标题
CDNF蛋白两个关键α螺旋调控CDNF分泌水平的定量分析
DOI：
10.1002/cbin.11082
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发表时间：
2019
影响因子：
3.9
通讯作者：
Gong Lei
中科院分区：
文献类型：
--
作者：
Liu Hao;Zhong Lin;Zhao Chunling;Tang Xiaolei;Yang Jun;Gong Lei
脑多巴胺神经营养因子（CDNF）可促进中脑多巴胺能神经元的存活，被认为是治疗帕金森病（PD）的有效药物。CDNF除了像其他经典的神经营养因子（NTFs）一样从细胞中分泌外，还可以定位于内质网（ER），作为ER应激反应蛋白调节ER应激。在我们以前的研究中，我们发现了两个螺旋，α1和α7，它们可以调节CDNF的细胞内运输和分泌。α1破坏可使CDNF蛋白明显滞留在ER内，而α7破坏则使大部分CDNF蛋白分泌到细胞外。而α1和α7则调节对侧的蛋白运输和分泌。然而，受α1或α7影响的CDNF的确切分泌水平尚未被灵敏地定量。在这项研究中，我们使用纳米荧光素酶来定量CDNF蛋白的分泌水平，以便我们可以评估α1和α7对CDNF分泌或功能的影响。
Cerebral dopamine neurotrophic factor (CDNF) has been considered as potent candidates for the therapy of Parkinson's disease (PD) for which can promote the survival of midbrain dopaminergic neurons. In addition to secret out from cells like other classical neurotrophic factors (NTFs), CDNF can locate in the endoplasmatic reticulum (ER), where they can function as ER stress response protein to regulate ER stress. In our previous studies, we have found two helices, α1 and α7, which can regulate the intracellular trafficking and secretion of CDNF. α1 distruction can significantly retain CDNF protein in the ER, but α7 distruction induce most CDNF protein secreting out the cells. Then α1 and α7 regulate protein trafficking and secretion in opposite side. However, the exact secretion level of CDNF affected by α1 or α7 have not been sensitively quantified. In this study, we used nanoluciferase to quantify the secretion level of CDNF protein so that we could evaluate the impact of α1 and α7 on CDNF secretion or function.