CD95 (APO-1/Fas) linkage to the actin cytoskeleton through ezrin in human T lymphocytes: a novel regulatory mechanism of the CD95 apoptotic pathway

CD95 (APO-1/Fas) is a member of the tumor necrosis factor receptor family, which can trigger apoptosis in a variety of cell types, However, little is known of the mechanisms underlying cell susceptibility to CD95-mediated apo ptosis, Here we show that human T cells that are susceptible to CD95-mediat ed apoptosis, exhibit a constitutive polarized morphology, and that CD95 co localizes with ezrin at the site of cellular polarization, In fact, CD95 co -immunoprecipitates with ezrin exclusively in lymphoblastoid CD4(+) T cells and primary long-term activated T lymphocytes, which are prone to CD95-med iated apoptosis, but not in short-term activated T lymphocytes, which are r efractory to the same stimuli, even expressing equal levels of CD95 on the cell membrane, Pre-treatment with ezrin antisense oligonucleotides specific ally protected from the CD95-mediated apoptosis, Moreover, we show that the actin cytoskeleton integrity is essential for this function. These finding s strongly suggest that the CD95 cell membrane polarization, through an ezr in-mediated association with the actin cytoskeleton, is a key intracellular mechanism in rendering human T lymphocytes susceptible to the CD95-mediate d apoptosis.