Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I

  title={Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I},
  author={Mathew L. Coleman and Erik Sahai and Margaret Yeo and Marta Bosch and Ann Dewar and Michael F. Olson},
  journal={Nature Cell Biology},
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… 
Actin-myosin–based contraction is responsible for apoptotic nuclear disintegration
It is shown that apoptotic nuclear disintegration requires actin-myosin contractile force and lamin proteolysis, making apoptosis analogous to, but distinct from, mitosis wherenuclear disintegration results from microtubule-based forces and from lamin phosphorylation and depolymerization.
ROCK-II-induced membrane blebbing and chromatin condensation require actin cytoskeleton.
Findings suggest that the activation of actin-myosin contractility is responsible for membrane blebbing and chromatin condensation and implicate ROCK II as a potential mediator of the morphological changes associated with apoptosis.
Independence of plasma membrane blebbing from other biochemical and biological characteristics of apoptotic cells.
Results indicate that blebbing of the plasma membrane occurs independently from other apoptotic changes and is not involved in the recognition and engulfment of apoptotic cells by macrophages.
Myosin light chain kinase plays a role in the regulation of epithelial cell survival
A newly discovered role for MLCK is demonstrated in the generation of pro-survival signals in both untransformed and transformed epithelial cells and supports previous work suggesting distinct cellular roles for Rho-kinase- and MLCk-dependent regulation of myosin II.
Cell motility through plasma membrane blebbing
It is proposed that in a physiological context, bleb-associated cell motility reflects a cell's response to reduced substratum adhesion and the importance of blebbing as a functional protrusion is underscores by the existence of multiple molecular mechanisms that govern actin-mediated bleb retraction.
Death‐associated protein kinase (DAPK) and signal transduction: blebbing in programmed cell death
The conservation of blebbing phenomenon suggests a fundamental role in metazoans and DAPK offers a door to further dissect this fascinating process.
Direct cleavage of ROCK II by granzyme B induces target cell membrane blebbing in a caspase-independent manner
It is shown here that grB directly cleaves ROCK II, a ROCK family member encoded by a separate gene and closely related to ROCK I, and this causes constitutive kinase activity and bleb formation, thus defining two independent pathways with similar phenotypic consequences in the cells.
The RhoA/ROCK-I/MLC pathway is involved in the ethanol-induced apoptosis by anoikis in astrocytes
It is shown that astrocytes exposed to ethanol undergo morphological changes associated with anoikis, including the peripheral reorganization of both focal adhesions and actin-myosin system, cell contraction, membrane blebbing and chromatin condensation.


Apoptotic Membrane Blebbing Is Regulated by Myosin Light Chain Phosphorylation
The model system described here should facilitate future studies of MLCK, Rho, and other signal transduction pathways activated during the execution phase of apoptosis and also implicate Rho signaling in these active morphological changes.
The actin-myosin cytoskeleton mediates reversible agonist-induced membrane blebbing.
Studies using cytoskeletal antagonistic drugs indicate that bleb formation and motility require actin remodeling concomitant with an activation of myosin II, and this aberrant activation and reorganization of the actin-myosin cytoskeleton is likely to have detrimental effects on acinar cell function.
Caspase-mediated activation of PAK2 during apoptosis: proteolytic kinase activation as a general mechanism of apoptotic signal transduction?
  • G. Bokoch
  • Biology
    Cell Death and Differentiation
  • 1998
PAK2 activity is implicated in regulation of the biochemistry and morphology of the apoptotic cell, and it is hypothesized that this may reflect their important role in regulating the controlled and orderly demise of the dying cell.
Formation of Actin Stress Fibers and Focal Adhesions Enhanced by Rho-Kinase
Rho-kinase appears to mediate signals from Rho and to induce the formation of stress fibers and focal adhesions.
Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase.
Results indicate that phosphorylation of LIM-kinase by ROCK and consequently increased phosphorylated of cofilin by LIM- Kinase contribute to Rho-induced reorganization of the actin cytoskeleton.
Regulation of the small GTP‐binding protein Rho by cell adhesion and the cytoskeleton
The results show that ECM, cytoskeletal structures and soluble factors all contribute to regulation of Rho activity, and both cytochalasin D and colchicine trigger Rho activation despite their opposite effects on stress fibers and focal adhesions.
Proteolytic activation of PKN by caspase-3 or related protease during apoptosis.
Results indicate that PKN is cleaved by caspase-3 or related protease during apoptosis, and the major proteolysis took place between the amino- terminal regulatory domain and the carboxyl-terminal catalytic domain, and it generated a constitutively active kinase fragment.
Rho GTPases and the actin cytoskeleton.
Members of the Rho family of small guanosine triphosphatases have emerged as key regulators of the actin cytoskeleton, and through their interaction with multiple target proteins, they ensure coordinated control of other cellular activities such as gene transcription and adhesion.
Regulation of Myosin Phosphatase by Rho and Rho-Associated Kinase (Rho-Kinase)
Rho appears to inhibit myosin phosphatase through the action of Rho-kinase, which is activated by GTP·RhoA, phosphorylation of MBS and MLC in NIH 3T3 cells.