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 proteins underlying this process; STIM is an ER Ca²+ sensor that interacts with Orai, an intrinsic, pore-forming protein of the CRAC channel. In heterologous expression 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 depletion with Tg, STIM2 aggregates and interacts selectively with Orai2. In contrast, Tg fails to aggregate STIM1 or enhance STIM1-mediated interactions with Orai proteins. Consistent with this biochemical characterization, stimulation of DCs with the adhesion molecule ICAM-1 selectively recruits STIM2 and Orai2 to the IS. Together, these data demonstrate a novel, STIM2-dependent SOCE signaling pathway in DCs.
Department of Pharmacology, Georgetown University, 3900 Reservoir Rd., NW, Washington, DC 20007, USA. bcb@georgetown.edu
Bidhan C
BC
Bandyopadhyay
Sandeep C
SC
Pingle
Gerard P
GP
Ahern
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D054992:Immunological Synapses / Q000187:drug effects / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000071741:ORAI2 Protein; D011485:Protein Binding / Q000187:drug effects; D020836:Protein Structure, Quaternary; D000071737:Stromal Interaction Molecule 1; D000071738:Stromal Interaction Molecule 2; D019284:Thapsigargin / Q000494:pharmacology
D015220:Calcium Channels; D008562:Membrane Glycoproteins; D000071741:ORAI2 Protein; C520431:Orai2 protein, mouse; C100757:Stim1 protein, mouse; C525024:Stim2 protein, mouse; D000071737:Stromal Interaction Molecule 1; D000071738:Stromal Interaction Molecule 2; D019284:Thapsigargin