A Golgi fragmentation pathway in neurodegeneration
A Golgi fragmentation pathway in neurodegeneration
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DOI：
10.1016/j.nbd.2007.08.015
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发表时间：
2008-02-01
影响因子：
6.1
通讯作者：
Lipton, Stuart A.
中科院分区：
文献类型：
--
作者：
Nakagomi, Saya;Barsoum, Mark J.;Lipton, Stuart A.
高尔基体处理细胞内蛋白，但在一些神经退行性疾病（如肌萎缩性侧索硬化症和阿尔茨海默病）的细胞凋亡过程中发生解体和断裂。众所周知，其他细胞器在细胞死亡途径中也起着重要作用。因此，我们假设高尔基断裂可能参与细胞死亡信号的转导。在这里，我们发现高尔基体碎片化和分散先于兴奋毒素、氧化/亚硝化损伤或内质网应激引发的神经元细胞死亡。高尔基蛋白相关蛋白Grasp65 c端片段的药物干预或过表达可抑制断裂并减少或延迟神经元细胞死亡。抑制线粒体或内质网细胞死亡途径也可减少高尔基体断裂，表明细胞器之间存在串扰，并提示高尔基体可能是细胞死亡的常见下游效应体。综上所述，这些发现暗示高尔基体是细胞死亡途径中应激信号的传感器。(C) 2007爱思唯尔公司版权所有。
The Golgi apparatus processes intracellular proteins, but undergoes disassembly and fragmentation during apoptosis in several neurodegenerative disorders such as amyotrophic lateral sclerosis and Alzheimer's disease. It is well known that other cytoplasmic organelles play important roles in cell death pathways. Thus, we hypothesized that Golgi fragmentation might participate in transduction of cell death signals. Here, we found that Golgi fragmentation and dispersal precede neuronal cell death triggered by excitotoxins, oxidative/nitrosative insults, or ER stress. Pharmacological intervention or overexpression of the C-terminal fragment of Grasp65, a Golgi-associated protein, inhibits fragmentation and decreases or delays neuronal cell death. Inhibition of mitochondrial or ER cell death pathways also decreases Golgi fragmentation, indicating crosstalk between organelles and suggesting that the Golgi may be a common downstream-effector of cell death. Taken together, these findings implicate the Golgi as a sensor of stress signals in cell death pathways. (C) 2007 Elsevier Inc. All rights reserved.