Fas stimulation of T lymphocytes promotes rapid intercellular exchange of death signals via membrane nanotubes

Peter D. Arkwright, Francesca Luchetti, Julien Tour, Charlotte Roberts, Rahna Ayub, Ana P. Morales, José J. Rodríguez, Andrew Gilmore, Barbara Canonico, Stefano Papa, Mauro Degli Esposti

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    Abstract

    The Fas/CD95 surface receptor mediates rapid death of various cell types, including autoreactive T cells with the potential for triggering autoimmunity. Here, we present novel aspects of Fas signalling that define a 'social' dimension to receptor-induced apoptosis. Fas stimulation rapidly induces extensive membrane nanotube formation between neighbouring T cells. This is critically dependent on Rho GTPases but not on caspase activation. Bidirectional transfer of membrane and cytosolic elements including active caspases can be observed to occur via these nanotubes. Nanotube formation and intercellular exchanges of death signals are defective in T lymphocytes from patients with autoimmune lymphoproliferative syndrome harbouring mutations in the Fas receptor. We conclude that nanotube-mediated exchanges constitute a novel form of intercellular communication that augments the propagation of death signalling between neighbouring T cells. © 2010 IBCB, SIBS, CAS All rights reserved.
    Original languageEnglish
    Pages (from-to)72-88
    Number of pages16
    JournalCell Research
    Volume20
    Issue number1
    DOIs
    Publication statusPublished - Jan 2010

    Keywords

    • Fas
    • Intercellular communication
    • Membrane nanotubes
    • T cells

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