Sustained calcium signalling and caspase-3 activation involve NMDA receptors in thymocytes in contact with dendritic cells

P Affatcati, O. Mignen, F. Jambou, M-C Potier, I Klingel-Schmitt, J Degrouard, S Peineau, E Gouadon, GL Collingridge, R Liblau, T Capiod, S Cohen-Kaminsky

Research output: Contribution to journalArticle (Academic Journal)peer-review

34 Citations (Scopus)

Abstract

L-glutamate, the major excitatory neurotransmitter, also has a role in non-neuronal tissues and modulates immune responses. Whether NMDA receptor (NMDAR) signalling is involved in T-cell development is unknown. In this study, we show that mouse thymocytes expressed an array of glutamate receptors, including NMDARs subunits. Sustained calcium (Ca(2+)) signals and caspase-3 activation in thymocytes were induced by interaction with antigen-pulsed dendritic cells (DCs) and were inhibited by NMDAR antagonists MK801 and memantine. NMDARs were transiently activated, triggered the sustained Ca(2+) signal and were corecruited with the PDZ-domain adaptor postsynaptic density (PSD)-95 to thymocyte-DC contact zones. Although T-cell receptor (TCR) activation was sufficient for relocalization of NMDAR and PSD-95 at the contact zone, NMDAR could be activated only in a synaptic context. In these T-DC contacts, thymocyte activation occurred in the absence of exogenous glutamate, indicating that DCs could be a physiological source of glutamate. DCs expressed glutamate, glutamate-specific vesicular glutamate transporters and were capable of fast glutamate release through a Ca(2+)-dependent mechanism. We suggest that glutamate released by DCs could elicit focal responses through NMDAR-signalling in T cells undergoing apoptosis. Thus, synapses between T and DCs could provide a functional platform for coupling TCR activation and NMDAR signalling, which might reflect on T-cell development and modulation of the immune response
Translated title of the contributionSustained calcium signalling and caspase-3 activation involve NMDA receptors in thymocytes in contact with dendritic cells
Original languageEnglish
Article numberEpub
Pages (from-to)99 - 108
Number of pages9
JournalCell Death and Differentiation
Volume1
DOIs
Publication statusPublished - Jan 2011

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