PMID- 15866891 OWN - NLM STAT- MEDLINE DCOM- 20050811 LR - 20230508 IS - 0021-9525 (Print) IS - 1540-8140 (Electronic) IS - 0021-9525 (Linking) VI - 169 IP - 3 DP - 2005 May 9 TI - STIM1, an essential and conserved component of store-operated Ca2+ channel function. PG - 435-45 AB - 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 (TG)-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 knockdown of STIM1 inhibited TG- or agonist-dependent Ca2+ entry in HEK293 or SH-SY5Y cells. Conversely, overexpression 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. FAU - Roos, Jack AU - Roos J AD - Torrey Pines Therapeutics, Inc., La Jolla, CA 92037, USA. FAU - DiGregorio, Paul J AU - DiGregorio PJ FAU - Yeromin, Andriy V AU - Yeromin AV FAU - Ohlsen, Kari AU - Ohlsen K FAU - Lioudyno, Maria AU - Lioudyno M FAU - Zhang, Shenyuan AU - Zhang S FAU - Safrina, Olga AU - Safrina O FAU - Kozak, J Ashot AU - Kozak JA FAU - Wagner, Steven L AU - Wagner SL FAU - Cahalan, Michael D AU - Cahalan MD FAU - Velicelebi, Gonul AU - Velicelebi G FAU - Stauderman, Kenneth A AU - Stauderman KA LA - eng GR - R01 NS014609/NS/NINDS NIH HHS/United States GR - R37 NS014609/NS/NINDS NIH HHS/United States GR - R56 NS014609/NS/NINDS NIH HHS/United States GR - NS14609/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20050502 PL - United States TA - J Cell Biol JT - The Journal of cell biology JID - 0375356 RN - 0 (Calcium Channels) RN - 0 (Drosophila Proteins) RN - 0 (Enzyme Inhibitors) RN - 0 (Membrane Proteins) RN - 0 (Neoplasm Proteins) RN - 0 (STIM1 protein, human) RN - 0 (Stim protein, Drosophila) RN - 0 (Stromal Interaction Molecule 1) RN - 67526-95-8 (Thapsigargin) RN - SY7Q814VUP (Calcium) SB - IM CIN - J Cell Biol. 2005 May 9;169(3):381-2. PMID: 15866892 MH - Animals MH - Calcium/*metabolism MH - Calcium Channels/*metabolism MH - Calcium Signaling/drug effects/*physiology MH - Cell Line MH - Cell Membrane/*metabolism MH - Conserved Sequence/physiology MH - Drosophila MH - Drosophila Proteins/genetics/isolation & purification/*metabolism MH - Enzyme Inhibitors/pharmacology MH - Evolution, Molecular MH - Humans MH - Jurkat Cells MH - Membrane Proteins/genetics/isolation & purification/*metabolism MH - Neoplasm Proteins/genetics/*metabolism MH - Patch-Clamp Techniques MH - RNA Interference MH - Stromal Interaction Molecule 1 MH - Thapsigargin/pharmacology PMC - PMC2171946 EDAT- 2005/05/04 09:00 MHDA- 2005/08/12 09:00 PMCR- 2005/11/09 CRDT- 2005/05/04 09:00 PHST- 2005/05/04 09:00 [pubmed] PHST- 2005/08/12 09:00 [medline] PHST- 2005/05/04 09:00 [entrez] PHST- 2005/11/09 00:00 [pmc-release] AID - jcb.200502019 [pii] AID - 200502019 [pii] AID - 10.1083/jcb.200502019 [doi] PST - ppublish SO - J Cell Biol. 2005 May 9;169(3):435-45. doi: 10.1083/jcb.200502019. Epub 2005 May 2.