Protein disulfide isomerase A6 promotes the repair of injured nerve through interactions with spastin.
Protein disulfide isomerase A6 promotes the repair of injured nerve through interactions with spastin.
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蛋白质二硫键异构酶 A6 通过与 spastin 相互作用促进受损神经的修复
DOI：
10.3389/fnmol.2022.950586
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发表时间：
2022
影响因子：
4.8
通讯作者：
Ji, Zhisheng
中科院分区：
文献类型：
--
作者：
Luo, Jianxian;Xie, Min;Peng, Cheng;Ma, Yanming;Wang, Ke;Lin, Gengxiong;Yang, Hua;Chen, Tianjun;Liu, Qiuling;Zhang, Guowei;Lin, Hongsheng;Ji, Zhisheng
维持适当的内质网（ER）稳态对有效的脊髓损伤（SCI）修复至关重要。在以前的报告中，蛋白质二硫键异构酶A6（PDIA 6）被证明是作为一个可逆的功能调节器的ER应激反应，而痉挛可以协调ER组织通过调节动态微管网络周围的这个细胞器。虽然PDIA 6和spastin都是ER的重要调节因子，但它们是否在SCI修复中相互作用仍需确定。在这里，蛋白质组学分析确定PDIA 6与SCI修复相关，蛋白质相互作用质谱进一步证实了PDIA 6和痉挛蛋白相互作用的能力。进一步进行下拉和免疫共沉淀测定以验证和表征这两种蛋白质之间的相互作用。基于RNA干扰的COS-7细胞PDIA 6基因敲除可抑制Spastin依赖性微管切割活性。PDIA 6也被发现促进受损神经元的修复，而痉挛素敲低则逆转了这种修复活性。总之，这些结果证实PDIA 6和痉挛蛋白共同作为神经修复的关键介质发挥作用，突出了它们作为促进SCI修复的有效靶点的潜在价值。
The maintenance of appropriate endoplasmic reticulum (ER) homeostasis is critical to effective spinal cord injury (SCI) repair. In previous reports, protein disulfide isomerase A6 (PDIA6) demonstrated to serve as a reversible functional modulator of ER stress responses, while spastin can coordinate ER organization through the modulation of the dynamic microtubule network surrounding this organelle. While both PDIA6 and spastin are thus important regulators of the ER, whether they interact with one another for SCI repair still needs to be determined. Here a proteomics analysis identified PDIA6 as being related to SCI repair, and protein interaction mass spectrometry further confirmed the ability of PDIA6 and spastin to interact with one another. Pull-down and co-immunoprecipitation assays were further performed to validate and characterize the interactions between these two proteins. The RNAi-based knockdown of PDIA6 in COS-7 cells inhibited the activity of spastin-dependent microtubule severing. PDIA6 was also found to promote injured neuron repair, while spastin knockdown reversed this reparative activity. Together, these results thus confirm that PDIA6 and spastin function together as critical mediators of nerve repair, highlighting their potential value as validated targets for efforts to promote SCI repair.
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影响因子：
6.2
作者：
Saraswat Ohri S;Howard RM;Liu Y;Andres KR;Shepard CT;Hetman M;Whittemore SR
通讯作者：
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影响因子：
3.8
作者：
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DOI：
10.1146/annurev-pathol-012513-104649
发表时间：
2015
期刊：
Annual review of pathology
影响因子：
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作者：
Oakes SA;Papa FR
通讯作者：
Papa FR
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