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

The cytotoxic synapse formed between cytotoxic T lymphocytes or natural killer cells expressing CD95L and target cells with CD95 on their surface is a key pathway for apoptosis induction by the immune system. Despite similarities with the immune synapse in antigen presenting cells, little is known a...

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Bibliographic Details
Main Authors: Sánchez, María (Author) , Gülcüler Balta, Gülce Sıla (Author)
Format: Article (Journal)
Language:English
Published: 24 May 2018
In: The FEBS journal
Year: 2018, Volume: 285, Issue: 15, Pages: 2813-2827
ISSN:1742-4658
DOI:10.1111/febs.14518
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1111/febs.14518
Verlag, lizenzpflichtig, Volltext: https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.14518
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Author Notes:María Florencia Sánchez, Fabronia Murad, Gülce S. Gülcüler Balta, Ana Martin-Villalba, Ana J. García-Sáez and Dolores C. Carrer
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Summary:The cytotoxic synapse formed between cytotoxic T lymphocytes or natural killer cells expressing CD95L and target cells with CD95 on their surface is a key pathway for apoptosis induction by the immune system. Despite similarities with the immune synapse in antigen presenting cells, little is known about the role of the spatiotemporal organization of agonistic proteins/receptor interactions for CD95 signaling. Here, we have developed an artificial cytotoxic synapse to examine how mobility and geometry of an anti-CD95 agonistic antibody affect receptor aggregation and mobility, ie the first step of receptor activation. By measuring the distribution, diffusion coefficient, and fraction of immobile CD95 receptor in living cells, we show that at short times, the initial activation of CD95 occurs locally and is limited to the contact region of the cytotoxic synapse. This anisotropic activation of apoptotic signaling supports a role for confined interactions on the efficiency of signal transduction that may have implications for biomedical applications of extrinsic apoptosis induction.
Item Description:Gesehen am 15.05.2020
Physical Description:Online Resource
ISSN:1742-4658
DOI:10.1111/febs.14518

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