Premium
CD95 (APO‐1/Fas) linkage to the actin cytoskeleton through ezrin in human T lymphocytes: a novel regulatory mechanism of the CD95 apoptotic pathway
Author(s) -
Parlato Stefania,
Giammarioli Anna Maria,
Logozzi Mariantonia,
Lozupone Francesco,
Matarrese Paola,
Luciani Francesca,
Falchi Mario,
Malorni Walter,
Fais Stefano
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.19.5123
Subject(s) - humanities , biology , art
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 apoptosis. Here we show that human T cells that are susceptible to CD95‐mediated apoptosis, exhibit a constitutive polarized morphology, and that CD95 colocalizes 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‐mediated apoptosis, but not in short‐term activated T lymphocytes, which are refractory to the same stimuli, even expressing equal levels of CD95 on the cell membrane. Pre‐treatment with ezrin antisense oligonucleotides specifically protected from the CD95‐mediated apoptosis. Moreover, we show that the actin cytoskeleton integrity is essential for this function. These findings strongly suggest that the CD95 cell membrane polarization, through an ezrin‐mediated association with the actin cytoskeleton, is a key intracellular mechanism in rendering human T lymphocytes susceptible to the CD95‐mediated apoptosis.