Journal
ELIFE
Volume 10, Issue -, Pages -Publisher
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.72051
Keywords
ORAI1; S-Acylation; Jurkat; T cell activation; None
Categories
Funding
- Swiss National Science Foundation [310030_189042, 310030B_176393 F, 310030_192608 F]
- European Research Council FP/2007-2013 [340260]
- Swiss National Science Foundation (SNF) [310030_189042, 310030B_176393, 310030_192608] Funding Source: Swiss National Science Foundation (SNF)
- European Research Council (ERC) [340260] Funding Source: European Research Council (ERC)
Ask authors/readers for more resources
This study reveals the critical role of ORAI1 channels in the immune synapse, with S-acylation playing a key regulatory role in channel trafficking and function at the synapse. Additionally, ORAI1 S-acylation is found to enhance TCR recruitment to the 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available