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Fig. 8. (A) CD95 on the T-cell can polarize towards a CD95L-expressing cell. Raji cells transiently transfected with CD95L-GFP (green) were incubated with Jurkat cells. The mixture was then settled on polylysine-coated coverslips and was finally labeled for CD95 (red). Note that CD95 is polarized towards the CD95L-expressing cell. (B) CD95 capping could regulate the availability of CD95 at immunological synapses. In this model, CD95 triggering by CD95L expressed on an encountering cell leads to ROCK-dependent receptor capping with concomitant aggregation of lipid rafts and F-actin by a mechanism leading to polarization of the cell. When CD95 is polarized towards the synapse, the target cell would eventually die by apoptosis (1). It is also possible that CD95 would cap at the distal pole and the cell would live, unaffected by the CD95L expressed on the surface of the other cell (2). CD95 capping could also be mediated independently of its ligand by signals from the T cell receptor, costimulatory ligands, or anti-tumor drugs that would affect the sensitivity to cell-mediated killing. (C) CD95 capping is ROCK-dependent and uncoupled from apoptosis signaling. ROCK signaling promotes cytoskeletal reorganization and lipid raft aggregation and capping of CD95. In type I cells, ROCK activation could be mediated by caspase cleavage, which is required for both CD95 capping and apoptosis. In the type II cell CD95 engagement leads to RhoA activation, which in turn activates ROCK, actin reorganization, lipid raft aggregation and CD95 capping. The apoptotic pathway, involving caspase activation is separated from the CD95 capping pathway in the type II cell. However, also in these cells ROCK signaling is only required for CD95 capping and not apoptosis. In addition, ROCK signaling suppresses apoptosis in a feedback loop.
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