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STIM1, an essential and conserved component of store-operated Ca2+ channel function.

  • Author(s): 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
  • et al.
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 (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.

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