Store-operated Ca2 signaling in dendritic cells occurs independently of STIM1

SOCE via CRAC channels is a critical signaling event in immune cells. Recent studies have identified key pro-teins underlying this process; STIM is an ER Ca2 sen-sor that interacts with Orai, an intrinsic, pore-forming protein of the CRAC channel. In heterologous expres-sion systems, STIM1 regulates SOCE by interacting with Orai1,-2, and-3. In native tissues, however, the precise roles of STIM and Orai proteins are not well defined. Here, we have investigated the molecular components of SOCE signaling in mouse DCs. We show that DCs predominantly express STIM2 and only very low levels of STIM1 compared with T lymphocytes. Upon store de-pletion with Tg, STIM2 aggregates and interacts selec-tively with Orai2. In contrast, Tg fails to aggregate STIM1 or enhance STIM1-mediated interactions with Orai proteins. Consistent with this biochemical charac-terization, stimulation of DCs with the adhesion mole-cule ICAM-1 selectively recruits STIM2 and Orai2 to the IS. Together, these data demonstrate a novel, STIM2-dependent SOCE signaling pathway in DCs. J. Leukoc. Biol. 89: 000–000; 2011