Coleman, M.L. et al. Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I. Nat. Cell Biol. 3, 339-345

Institute of Cancer Research, Londinium, England, United Kingdom
Nature Cell Biology (Impact Factor: 20.06). 05/2001; 3(4):339-45. DOI: 10.1038/35070009
Source: PubMed

ABSTRACT The execution phase of apoptosis is characterized by marked changes in cell morphology that include contraction and membrane blebbing. The actin-myosin system has been proposed to be the source of contractile force that drives bleb formation, although the biochemical pathway that promotes actin-myosin contractility during apoptosis has not been identified. Here we show that the Rho effector protein ROCK I, which contributes to phosphorylation of myosin light-chains, myosin ATPase activity and coupling of actin-myosin filaments to the plasma membrane, is cleaved during apoptosis to generate a truncated active form. The activity of ROCK proteins is both necessary and sufficient for formation of membrane blebs and for re-localization of fragmented DNA into blebs and apoptotic bodies.

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    • "Considering that TNF-α is known to induce the disruption of actin cytoskeleton in endothelial cells [29] [30] and that the disruption of actin cytoskeleton is tightly related with the release of membrane vesicles [7] [31], it is possible that TNF-α activation caused the enlargement of the spaces among cytoskeletal filaments due to the local relaxation/ disruption of actin cytoskeleton and that some cytoplasmic matters were squeezed out through the enlarged spaces during air drying to form the particle-like structures. Taken together, our data indicate that cell-bound membrane vesicles are hemisphere-shaped and that the actin cortical network lies at the cytosolic opening of a vesicle instead of being closely attached to the inner side of the vesicle membrane. "
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    • "Several differences in activation and cellular function between these isoforms have also been identified. Specifically ROCK-1 is known to be cleaved via caspase-3 activity and ROCK-2 by granzyme B [Coleman et al., 2001]. ROCK-1 inactivation has been linked to terminal fusion of myoblasts [Nishiyama et al., 2004], whereas ROCK-2 has been suggested to be the dominant isoform required for myoblast migration, however, their roles differ across cell types and are specific to external guidance cues from the substrate [Yamada et al., 2003; Pelosi et al., 2007; Goetsch et al., 2011]. "
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    • "In this latter case, release is initiated by a sustained rise in intracellular calcium [1–3, 6]. The mechanism of calcium-stimulated microparticle release has been explored most extensively in platelets and erythrocytes where release requires reorganization of the cytoskeleton, translocation of phosphatidylserine (PS) and other phospholipids to the outer face of the cell membrane, and enhanced permeability to potassium with associated osmotic effects [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28]. In addition , recent work with erythrocytes has demonstrated that vesicle shedding also depends on physical characteristic of the cell membrane, which can be detected with fluorescent "
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