RT Journal Article SR Electronic T1 Cell-intrinsic activation of Orai1 regulates human T cell motility JF bioRxiv FD Cold Spring Harbor Laboratory SP 128595 DO 10.1101/128595 A1 Tobias X. Dong A1 Milton L. Greenberg A1 Sabrina Leverrier A1 Ying Yu A1 Ian Parker A1 Joseph L. Dynes A1 Michael D. Cahalan YR 2017 UL http://biorxiv.org/content/early/2017/04/18/128595.abstract AB 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.