Early activation of CD95 is limited and localized to the cytotoxic synapse

MURAD, FABRONIA; GARCÍA-SÁEZ, ANA J.; SÁNCHEZ, M. FLORENCIA; MARTIN-VILLALBA, ANA; GÜLCÜLER BALTA, GÜLCE S.; CARRER, DOLORES C.

FEBS JOURNAL

WILEY-BLACKWELL PUBLISHING, INC

Año: 2018 vol. 285 p. 2813 - 2827

1742-464X

The cytotoxic synapse formed between cytotoxic T lymphocytes or Natural Killer cells expressingCD95L and target cells with CD95 on their surface is a key pathway for apoptosis induction by theimmune system. Despite similarities with the immune synapse in antigen presenting cells, little is knownabout the role of the spatiotemporal organization of agonistic proteins/receptor interactions for CD95signaling. Here we have developed an artificial cytotoxic synapse to examine how mobility and geometryof an anti-CD95 agonistic antibody affect receptor aggregation and mobility, ie the first step of receptoractivation. By measuring the distribution, diffusion coefficient and fraction of immobile CD95 receptor inliving cells, we show that at short times, the initial activation of CD95 occurs locally and is limited to thecontact region of the cytotoxic synapse. This anisotropic activation of apoptotic signaling supports a rolefor confined interactions on the efficiency of signal transduction that may have implications forbiomedical applications of extrinsic apoptosis induction