Document Detail


Store-operated Ca²+ signaling in dendritic cells occurs independently of STIM1.
MedLine Citation:
PMID:  20971921     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Bidhan C Bandyopadhyay; Sandeep C Pingle; Gerard P Ahern
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-10-22
Journal Detail:
Title:  Journal of leukocyte biology     Volume:  89     ISSN:  1938-3673     ISO Abbreviation:  J. Leukoc. Biol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-12     Completed Date:  2011-02-08     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  8405628     Medline TA:  J Leukoc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  57-62     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Georgetown University, 3900 Reservoir Rd., NW, Washington, DC 20007, USA. bcb@georgetown.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Calcium Channels / metabolism
Calcium Signaling* / drug effects
Dendritic Cells / cytology,  drug effects,  metabolism*
Immunological Synapses / drug effects,  metabolism
Membrane Glycoproteins / chemistry,  metabolism
Mice
Mice, Inbred C57BL
Protein Binding / drug effects
Protein Structure, Quaternary
Thapsigargin / pharmacology
Chemical
Reg. No./Substance:
0/Calcium Channels; 0/Membrane Glycoproteins; 0/Orai2 protein, mouse; 0/Stim1 protein, mouse; 0/Stim2 protein, mouse; 67526-95-8/Thapsigargin
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