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- Title
STIM 1, an essential and conserved component of store-operated Ca<sub>2+</sub> channel function.
- Authors
Roos, Jack; Digregorio, Paul J.; Yeromin, Andriy V.; Ohlsen, Kari; Lioudyno, Maria; Zhang, Shenyuan; Safrina, Olga; Kozak, J. Ashot; Wagner, Steven L.; Cahalan, Michael D.; Veliçelebi, Gönül; Stauderman, Kenneth A.
- Abstract
Store-operated Ca2+ (SOC) channels regulate many cellular processes, but the underlying molecular components are not well defined. Using an RNA interference (RNAi)-based screen to identify genes that alter thapsigargin (IG)-dependent Ca2+ entry, we discovered a required and conserved role of Stim in SOC influx. RNAi-mediated knockdown of Stim in Drosophila S2 cells significantly reduced TG-dependent Ca2+ entry Patch-clamp recording revealed nearly complete suppression of the Drosophila Ca2+ release-activated Ca2+ (CRAC) current that has biophysical characteristics similar to CRAC current in human T cells. Similarly, knockdown of the human homologue STIM1 significantly reduced CRAC channel activity in Jurkat T cells. RNAi-mediated knock- down of STIM1 inhibited IG- or agonist-dependent Ca2+ entry in HEK293 or SH-SY5Y cells. Conversely, over- expression of STIM1 in HEK293 cells modestly enhanced TG-induced Ca2+ entry. We propose that STIM1, a ubiquitously expressed protein that is conserved from Drosophila to mammalian cells, plays an essential role in SOC influx and may be a common component of SOC and CRAC channels.
- Publication
Journal of Cell Biology, 2005, Vol 169, Issue 3, p435
- ISSN
0021-9525
- Publication type
Academic Journal
- DOI
10.1083/jcb.200502019