| Popis: |
Recent studies indicate that the reorganization of receptor molecules in distinct domains of the cell membrane constitutes an important and general mechanism that is required for the initiation of signaling via various receptor molecules. Studies on the CD95 receptor might serve as a paradigm for the mechanism mediating receptor clustering/aggregation. These studies revealed activation of the acid sphingomyelinase and a release of ceramide in the outer leaflet of the cell membrane upon stimulation of CD95. The unique biophysical properties of ceramide trigger the formation of large ceramide-enriched membrane platforms that serve to trap and cluster the receptor. This process results in a high density of CD95 within a distinct area of the cell membrane and amplifies the primary signal generated by binding of the CD95 ligand and, thus, permits the induction of apoptosis. Furthermore, ceramide-enriched membrane domains mediate the assembling of the receptor with intracellular signaling molecules, in particular FADD, caspase 8, and the potassium channel Kvl.3 that finally mediate apoptosis initiated by CD95 ligation. |
