Mukherjee Shaeri, Chiu Raymond, Leung Som-Ming, Shields Dennis
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Traffic. 2007 Apr;8(4):369-78. doi: 10.1111/j.1600-0854.2007.00542.x.
The Golgi apparatus undergoes irreversible fragmentation during apoptosis, in part as a result of caspase-mediated cleavage of several Golgi-associated proteins. However, Golgi structure and orientation is also regulated by the cytoskeleton and cytoskeletal changes have been implicated in inducing apoptosis. Consequently, we have analyzed the role of actin filaments and microtubules in apoptotic Golgi fragmentation. We demonstrate that in Fas receptor-activated cells, fragmentation of the Golgi apparatus was an early event that coincided with release of cytochrome c from mitochondria. Significantly, Golgi fragmentation preceded major changes in the organization of both the actin cytoskeleton and microtubules. In staurosporine-treated cells, actin filament organization was rapidly disrupted; however, the Golgi apparatus maintained its juxtanuclear localization and underwent complete fragmentation only at later times. Attempts to stabilize actin filaments with jasplakinolide prior to treatment with staurosporine did not prevent Golgi fragmentation. Finally, in response to Fas receptor activation or staurosporine treatment the levels of beta-actin or alpha-tubulin remained unaltered, whereas several Golgi proteins, p115 and golgin-160, underwent caspase-mediated cleavage. Our data demonstrate that breakdown of the Golgi apparatus is an early event during apoptosis that occurs independently of major changes to the actin and tubulin cytoskeleton.
在细胞凋亡过程中，高尔基体经历不可逆的碎片化，部分原因是几种与高尔基体相关的蛋白质被半胱天冬酶介导裂解。然而，高尔基体的结构和方向也受细胞骨架调控，并且细胞骨架变化与诱导细胞凋亡有关。因此，我们分析了肌动蛋白丝和微管在凋亡性高尔基体碎片化中的作用。我们证明，在Fas受体激活的细胞中，高尔基体的碎片化是一个早期事件，与细胞色素c从线粒体释放同时发生。重要的是，高尔基体碎片化先于肌动蛋白细胞骨架和微管组织的主要变化。在星形孢菌素处理的细胞中，肌动蛋白丝组织迅速被破坏；然而，高尔基体保持其核周定位，仅在后期才发生完全碎片化。在用星形孢菌素处理之前用茉莉酸内酯稳定肌动蛋白丝的尝试并不能阻止高尔基体碎片化。最后，响应Fas受体激活或星形孢菌素处理，β-肌动蛋白或α-微管蛋白的水平保持不变，而几种高尔基体蛋白，p115和高尔基体蛋白-160，发生了半胱天冬酶介导的裂解。我们的数据表明，高尔基体的解体是细胞凋亡过程中的一个早期事件，其发生独立于肌动蛋白和微管蛋白细胞骨架的主要变化。
