Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I.
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.
Coleman
M L
ML
CRC Centre for Cell and Molecular Biology, Chester Beatty Laboratories, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
Sahai
E A
EA
Yeo
M
M
Bosch
M
M
Dewar
A
A
Olson
M F
MF
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002462:Cell Membrane / Q000473:pathology; D004247:DNA / Q000378:metabolism; D053938:DNA Fragmentation; D004789:Enzyme Activation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D014407:Tumor Cells, Cultured; D054460:rho-Associated Kinases
D061945:Caspase Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011993:Recombinant Fusion Proteins; D004247:DNA; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020169:Caspases