S-acylation by ZDHHC20 targets ORAI1 channels to lipid rafts for efficient Ca2+ signaling by Jurkat T cell receptors at the immune synapse
Copyright policy )S-acylation by ZDHHC20 targets ORAI1 channels to lipid rafts for efficient Ca2+ signaling by Jurkat T cell receptors at the immune synapse
Efficient immune responses require Ca2+ fluxes across ORAI1 channels during engagement of T cell receptors (TCR) at the immune synapse (IS) between T cells and antigen presenting cells. Here, we show that ZDHHC20-mediated S-acylation of the ORAI1 channel at residue Cys143 promotes TCR recruitment and signaling at the IS. Cys143 mutations reduced ORAI1 currents and store-operated Ca2+ entry in HEK-293 cells and nearly abrogated long-lasting Ca2+ elevations, NFATC1 translocation, and IL-2 secretion evoked by TCR engagement in Jurkat T cells. The acylation-deficient channel remained in cholesterol-poor domains upon enforced ZDHHC20 expression and was recruited less efficiently to the IS along with actin and TCR. Our results establish S-acylation as a critical regulator of ORAI1 channel trafficking and function at the IS and reveal that ORAI1 S-acylation enhances TCR recruitment to the synapse.
- University of Geneva Switzerland
- École Polytechnique Fédérale de Lausanne EPFL Switzerland
- Yonsei University Korea (Republic of)
- Swiss National Science Foundation Switzerland
Calcium / metabolism, ORAI1 Protein / metabolism, ORAI1 Protein, QH301-705.5, Science, Acylation, T-Lymphocytes, Immunology, Receptors, Antigen, T-Cell, Antigen-Presenting Cells, 612, Acyltransferases / genetics, Jurkat Cells, Immunology and Inflammation, Membrane Microdomains, None, Humans, Biology (General), Antigen-Presenting Cells / metabolism, Jurkat Cells / metabolism, Inflammation, Jurkat, T cell activation, Q, R, Acyltransferases / metabolism, ORAI1, HEK293 Cells, Membrane Microdomains / metabolism, ORAI1 Protein / genetics, Medicine, Receptors, Antigen, T-Cell / metabolism, S-Acylation, Calcium, Sulfur / metabolism, T-Lymphocytes / metabolism, Acyltransferases, Sulfur, Signal Transduction, ddc: ddc:612
Calcium / metabolism, ORAI1 Protein / metabolism, ORAI1 Protein, QH301-705.5, Science, Acylation, T-Lymphocytes, Immunology, Receptors, Antigen, T-Cell, Antigen-Presenting Cells, 612, Acyltransferases / genetics, Jurkat Cells, Immunology and Inflammation, Membrane Microdomains, None, Humans, Biology (General), Antigen-Presenting Cells / metabolism, Jurkat Cells / metabolism, Inflammation, Jurkat, T cell activation, Q, R, Acyltransferases / metabolism, ORAI1, HEK293 Cells, Membrane Microdomains / metabolism, ORAI1 Protein / genetics, Medicine, Receptors, Antigen, T-Cell / metabolism, S-Acylation, Calcium, Sulfur / metabolism, T-Lymphocytes / metabolism, Acyltransferases, Sulfur, Signal Transduction, ddc: ddc:612
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