MPP+ impairs autophagic clearance of alpha-synuclein by impairing the activity of dynein
MPP+ impairs autophagic clearance of alpha-synuclein by impairing the activity of dynein
复制标题
MPP 通过损害动力蛋白的活性来损害 α-突触核蛋白的自噬清除
DOI：
10.1097/wnr.0b013e32832986c4
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发表时间：
2009-04-22
期刊：
影响因子：
1.7
通讯作者：
Liu, Chun-Feng
中科院分区：
文献类型：
--
作者：
Cai, Zeng-Lin;Shi, Ji-Jun;Liu, Chun-Feng
越来越多的证据表明，动力蛋白在自噬清除错误折叠的蛋白质中起重要作用。在这里，我们表明，1-甲基-4-苯基吡啶鎓（MPP+）的细胞治疗引起α-突触核蛋白的过度表达和聚集，导致自噬空泡的积累和LC 3-II的招聘这些空泡在细胞质中。MPP+处理后，动力蛋白表达减少，主要聚集在细胞质的周边，失去了与α-突触核蛋白和lamp 1的共定位，表明动力蛋白失去了其在攻击体形成中的功能，并且不能将自噬体和溶酶体返回到细胞中心进行降解。我们认为动力蛋白在自噬清除聚集蛋白中起着重要作用。NeuroReport 20：569-573（C）2009年威科健康垂直酒吧Lippincott威廉姆斯&威尔金斯。
Increasing evidence suggests that dynein has an important role in the clearance of misfolded proteins by autophagy. Here we show that treatment of cells with 1-methyl-4-phenylpyridinium (MPP+) cause alpha-synuclein overexpression and aggregation, leading to the accumulation of autophagic vacuoles and the recruitment of LC3-II to these vacuoles in the cytoplasm. After MPP+ treatment dynein expression decreased and was mainly aggregated at the periphery of cytoplasm and lost its colocalization with alpha-synuclein and lamp1, indicating that dynein lost its function in the aggresome formation and failed to return autophagosome and lysosomes to the center of the cell for degradation. We consider that dynein plays an important role in the autophagic clearance of aggregate-prone proteins. NeuroReport 20:569-573 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.