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.
CRC Centre for Cell and Molecular Biology, Chester Beatty Laboratories, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
M L
ML
Coleman
E A
EA
Sahai
M
M
Yeo
M
M
Bosch
A
A
Dewar
M F
MF
Olson
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