Journal
EXPERIMENTAL CELL RESEARCH
Volume 312, Issue 1, Pages 5-15Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2005.09.012
Keywords
Rho kinase; ROCK; fragmentation; apoptotic body; execution phase; apoptosis; phagocytosis; actin; myosin; cytoskeleton
Categories
Funding
- NIA NIH HHS [T32AG00255] Funding Source: Medline
- NINDS NIH HHS [NS32465] Funding Source: Medline
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS032465] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [T32AG000255] Funding Source: NIH RePORTER
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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.
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