Research ArticleCalcium signaling

ORAI1, STIM1/2, and RYR1 shape subsecond Ca2+ microdomains upon T cell activation

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Science Signaling  18 Dec 2018:
Vol. 11, Issue 561, eaat0358
DOI: 10.1126/scisignal.aat0358

A snapshot after T cell activation

Stimulation of the T cell receptor (TCR) initially elicits local Ca2+ signals at the plasma membrane that propagate to trigger global Ca2+ signals that fully activate T cells. Using high-resolution imaging and biochemical techniques to analyze mouse T cells and a human T cell line, Diercks et al. identified the proteins that generate Ca2+ signals within the first second after T cell activation. In unstimulated cells, the plasma membrane–localized Ca2+ channel ORAI1 was constitutively associated with the ER-localized Ca2+ sensors STIM1 and STIM2 and generated brief, spontaneous, and small-amplitude Ca2+ signals. Stimulation of the TCR induced production of the second messenger NAADP, which promoted Ca2+ release through the ryanodine receptor RYR1, ensuring the Ca2+ influx required for the sustained T cell activation. These results identify the Ca2+-handling proteins and show how they are poised to respond to TCR stimulation.

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