Research ArticleCalcium signaling

Frontrunners of T cell activation: Initial, localized Ca2+ signals mediated by NAADP and the type 1 ryanodine receptor

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Sci. Signal.  13 Oct 2015:
Vol. 8, Issue 398, pp. ra102
DOI: 10.1126/scisignal.aab0863

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Calcium signals down to the millisecond

Engagement of the T cell receptor (TCR) stimulates Ca2+ signaling, which is required for T cell activation. The earliest Ca2+ signals are short-lived and localized near the sites of TCR stimulation; later events are longer-lasting and more widespread. Wolf et al. used a combination of fluorescent indicator dyes and microscopy to perform high-resolution imaging of Ca2+ signals that occurred within milliseconds of the TCR stimulation of live mouse and human T cells. Microinjection of cells with the second messenger NAADP, which is generated upon T cell activation, produced a similar spatiotemporal pattern of Ca2+ signals in the absence of TCR activation. Both TCR- and NAADP-dependent signals were markedly reduced by depletion of ryanodine receptors, which are localized in the endoplasmic reticulum, implicating this internal calcium store as a source for the early Ca2+ signals required for T cell activation.