Rho kinase regulates fragmentation and phagocytosis of apoptotic cells
Rho kinase regulates fragmentation and phagocytosis of apoptotic cells
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DOI：
10.1016/j.yexcr.2005.09.012
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发表时间：
2006-01-01
影响因子：
3.7
通讯作者：
Pittman, RN
中科院分区：
文献类型：
--
作者：
Orlando, KA;Stone, NL;Pittman, RN
在细胞凋亡的执行阶段，细胞经历细胞质和细胞核的变化，为死亡和吞噬做准备。执行阶段的终点是细胞凝聚成单个凋亡小体或分裂成多个凋亡小体。碎片被认为有助于吞噬；然而，调控碎片化的机制尚不清楚。Rho激酶的一种异构体ROCK-I通过激活肌动蛋白-肌球蛋白收缩来驱动膜起泡；这提出了rock - 1可能调节其他执行阶段事件的可能性，例如细胞分裂。在这里，我们发现COS-7细胞在凋亡过程中分裂成许多小的凋亡小体；使用岩石抑制剂（Y-27632或H-1152）可防止碎裂。干预肌动蛋白收缩的药物Latrunculin B和blebbistatin也能抑制碎片化。在细胞凋亡过程中，ROCK-I被半胱天冬酶裂解并激活，而ROCK-II不被激活，而是易位到细胞骨架部分。siRNA敲低ROCK-I而不敲低ROCK-II可抑制死亡细胞的断裂，这与ROCK-I是凋亡断裂所必需的一致。最后，在ROCK抑制剂Y-27632存在下死亡的细胞不能被有效吞噬。这些数据表明，ROCK在凋亡细胞的破碎和吞噬中起着至关重要的作用。(c) 2005爱思唯尔公司版权所有。
During the execution phase of apoptosis, a cell undergoes cytoplasmic and nuclear changes that prepare it for death and phagocytosis. The end-point of the execution phase is condensation into a single apoptotic body or fragmentation into multiple apoptotic bodies. Fragmentation is thought to facilitate phagocytosis; however, mechanisms regulating fragmentation are unknown. An isoform of Rho kinase, ROCK-I, drives membrane blebbing through its activation of actin-myosin contraction; this raises the possibility that ROCK-I may regulate other execution phase events, such as cellular fragmentation. Here, we show that COS-7 cells fragment into a number of small apoptotic bodies during apoptosis; treating with ROCK inhibitors (Y-27632 or H-1152) prevents fragmentation. Latrunculin B and blebbistatin, drugs that interfere with actin-myosin contraction, also inhibit fragmentation. During apoptosis, ROCK-I is cleaved and activated by caspases, while ROCK-II is not activated, but rather translocates to a cytoskeletal fraction. siRNA knock-down of ROCK-I but not ROCK-II inhibits fragmentation of dying cells, consistent with ROCK-I being required for apoptotic fragmentation. Finally, cells dying in the presence of the ROCK inhibitor Y-27632 are not efficiently phagocytized. These data show that ROCK plays an essential role in fragmentation and phagocytosis of apoptotic cells. (c) 2005 Elsevier Inc. All rights reserved.