CD95 capping is ROCK-dependent and dispensable for apoptosis.
Upon engagement, the CD95 receptor is rapidly clustered into cellular 'caps'. This receptor capping is one of the first events to take place following activation and it has been proposed to be important for the initiation of apoptotic signaling. As the biological roles of CD95 capping are still elusive, we explored in detail the role of capping in induction of apoptosis in lymphocytes. CD95 capping was shown to be uncoupled from apoptosis, as apoptosis could occur in the absence of CD95 capping and, vice versa, capping could occur without inducing apoptosis. CD95 capping occurred concomitantly with reorganization of the actin cytoskeleton and aggregation of lipid rafts. While inhibition of actin polymerization and caspase-8 activity had cell type-specific effects on capping in type I and type II cells, the rapid CD95-mediated cellular polarization, as visualized by the orchestrated reorganization of CD95, F-actin and lipid rafts, was shown to be dependent on signaling by Rho kinase (ROCK) in both cell types, however, by distinct activation mechanisms in the respective cell type. CD95 activated RhoA exclusively in the type II cell, whereas ROCK activation was caspase-dependent in the type I cell. Taken together, our results imply that CD95 capping and the subsequent cellular polarization is a ROCK signaling-regulated process that does not correlate with the induction of apoptosis, but is more likely to be involved in the emerging non-apoptotic functions of CD95.
Söderström
Thomas S
TS
Department of Biology, Abo Akademi University, FI-20520, Turku, Finland.
Nyberg
Sofia D
SD
Eriksson
John E
JE
D000199:Actins / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology*; D053181:Caspase 8; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D016764:Cell Polarity / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D021962:Membrane Microdomains / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology; D019014:fas Receptor / Q000378:metabolism*; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D000199:Actins; D047908:Intracellular Signaling Peptides and Proteins; D019014:fas Receptor; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; C505530:CASP8 protein, human; D053181:Caspase 8; D020169:Caspases; D020742:rhoA GTP-Binding Protein