Ezrin is a negative regulator of death receptor-induced apoptosis.
Ezrin links cortical actin filaments with the cell membrane, and has a critical role in many membrane-initiated events. Fas is directly associated with ezrin, but conflicting results have been reported for the involvement of ezrin in Fas-induced cell death. In this study we show that ezrin was associated with Fas in T cells before stimulation and was released shortly after Fas ligand (FasL) engagement. The knockdown of ezrin moderately increased Fas-triggered or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-triggered cell death in normal T lymphocytes and in H9 cells, but had no effect on death receptor-induced apoptosis in type II cells, such as Jurkat and CEM. Expression of a dominant-negative form of ezrin also led to an increased Fas-induced apoptosis in H9 cells. Ezrin deficiency did not affect the internalization of Fas after Fas ligation. Instead, an enhanced formation of death-inducing signaling complex (DISC) was observed in H9 cells with ezrin knockdown, leading to accelerated caspase-8 activation. Together, our results suggest that ezrin has a negative role in the recruitment of Fas into signaling complexes in type I T cells. Loss of ezrin likely removes the constraint imposed by ezrin and facilitates the assembly of death receptor complex in T cells.
Kuo
W-C
WC
Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
Yang
K-T
KT
Hsieh
S-L
SL
Lai
M-Z
MZ
D017209:Apoptosis / Q000502:physiology*; D053181:Caspase 8 / Q000378:metabolism; D016923:Cell Death; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D053222:Fas Ligand Protein / Q000276:immunology* / Q000502:physiology; D006801:Humans; D053218:Receptors, Death Domain / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes; D053221:TNF-Related Apoptosis-Inducing Ligand; D000099149:Ezrin
D053181:Caspase 8; D003598:Cytoskeletal Proteins; D053222:Fas Ligand Protein; D053218:Receptors, Death Domain; D053221:TNF-Related Apoptosis-Inducing Ligand; D000099149:Ezrin