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Publication : Intermittent Ca<sup>2+</sup> signals mediated by Orai1 regulate basal T cell motility.

First Author  Dong TX Year  2017
Journal  Elife Volume  6
PubMed ID  29239723 Mgi Jnum  J:254964
Mgi Id  MGI:6111042 Doi  10.7554/eLife.27827
Citation  Dong TX, et al. (2017) Intermittent Ca(2+) signals mediated by Orai1 regulate basal T cell motility. Elife 6:e27827
abstractText  Ca(2+) influx through Orai1 channels is crucial for several T cell functions, but a role in regulating basal cellular motility has not been described. Here, we show that inhibition of Orai1 channel activity increases average cell velocities by reducing the frequency of pauses in human T cells migrating through confined spaces, even in the absence of extrinsic cell contacts or antigen recognition. Utilizing a novel ratiometric genetically encoded cytosolic Ca(2+) indicator, Salsa6f, which permits real-time monitoring of cytosolic Ca(2+) along with cell motility, we show that spontaneous pauses during T cell motility in vitro and in vivo coincide with episodes of cytosolic Ca(2+) signaling. Furthermore, lymph node T cells exhibited two types of spontaneous Ca(2+) transients: short-duration ''sparkles'' and longer duration global signals. Our results demonstrate that spontaneous and self-peptide MHC-dependent activation of Orai1 ensures random walk behavior in T cells to optimize immune surveillance.
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