Decay - Accelerating Factor - Release from Cell Membrane

Decay-accelerating factor (DAF) ~ is a membrane protein that inhibits amplification of the complement cascade on cell surfaces. By binding to C3b or C4b complement fragments that accidentally deposit on the cell membrane, DAF blocks the assembly of both the classical and alternative C3 and C5 convertases (1-3). In this manner, DAF protects host cells from damage by autologous complement. DAF is deficient in a rare acquired disorder of blood cells, paroxysmal nocturnal hemoglobinuria (PNH) (4, 5), characterized by increased sensitivity of erythrocytes to complement-mediated lysis (6). The DAF-deficient blood cells probably originate from the expansion of abnormal bone marrow clones (7, 8), but the nature of the molecular defect is unknown. Other membrane abnormalities have been found in PNH, including the absence of acetylcholinesterase (ACHE) in the population of complement-sensitive erythrocytes (9). These two apparently unrelated proteins, DAF and ACHE, share the property of being able, in a purified form, to reincorporate into the lipid bilayer of cell membranes or into phospholipid vesicles (3, 10, 11). The amphipathic properties of AChE are known to be due to an unusual type of membrane anchor, the diacylglycerol moiety of a phosphatidylinositol (PI) molecule that is covalently attached to the protein (11, 12). The structure of this membrane-seeking domain was revealed, in part, by the observation that AChE is released from the cell surface by phosphatidylinositol-specific phosholipase C (PIPLC) (13, 14). In view of the above-mentioned similarity between the amphipathic properties of DAF