%0 Journal Article %A Tobias X. Dong %A Milton L. Greenberg %A Sabrina Leverrier %A Ying Yu %A Ian Parker %A Joseph L. Dynes %A Michael D. Cahalan %T Cell-intrinsic activation of Orai1 regulates human T cell motility %D 2017 %R 10.1101/128595 %J bioRxiv %P 128595 %X Ca2+ signaling through the store-operated Ca2+ channel, Orai1, is crucial for T cell function, but a role in regulating T cell motility in lymph nodes has not been previously reported. Tracking human T cells in immunodeficient mouse lymph nodes and in microfabricated PDMS channels, we show that inhibition of Orai1 channel activity with a dominant-negative Orai1-E106A construct increases average T cell velocities by reducing the frequency of pauses in motile T cells. Orai1-dependent motility arrest occurs spontaneously during confined motility in vitro, even in the absence of extrinsic cell contacts or antigen recognition. Utilizing a novel ratiometric genetically encoded cytosolic Ca2+ indicator, Salsa6f, we show these spontaneous pauses during T cell motility in vitro coincide with episodes of spontaneous cytosolic Ca2+ signaling. Our results demonstrate that Orai1, activated in a cell-intrinsic manner, regulates T cell motility patterns that accompany immune surveillance. %U https://www.biorxiv.org/content/biorxiv/early/2017/04/18/128595.full.pdf