TY - JOUR T1 - Cell-intrinsic activation of Orai1 regulates human T cell motility JF - bioRxiv DO - 10.1101/128595 SP - 128595 AU - Tobias X. Dong AU - Milton L. Greenberg AU - Sabrina Leverrier AU - Ying Yu AU - Ian Parker AU - Joseph L. Dynes AU - Michael D. Cahalan Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/04/18/128595.abstract N2 - 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. ER -