STIM1, but not STIM2, is required for proper agonist-induced Ca2+ signaling

Cell Calcium. 2010 Aug-Sep;48(2-3):161-7. doi: 10.1016/j.ceca.2010.08.003.

Abstract

The stromal interaction molecules STIM1 and STIM2 sense a decreasing Ca(2+) concentration in the lumen of the endoplasmic reticulum and activate Ca(2+) channels in the plasma membrane. In addition, at least 2 reports suggested that STIM1 may also interact with the inositol 1,4,5-trisphosphate (IP(3)) receptor. Using embryonic fibroblasts from Stim1(-/-), Stim2(-/-) and wild-type mice, we now tested the hypothesis that STIM1 and STIM2 would also regulate the IP(3) receptor. We investigated whether STIM1 or STIM2 would be the luminal Ca(2+) sensor that controls the loading dependence of the IP(3)-induced Ca(2+) release. Partial emptying of the stores in plasma-membrane permeabilized cells resulted in an increased EC(50) and a decreased Hill coefficient for IP(3)-induced Ca(2+) release. This effect occurred both in the presence and absence of STIM proteins, indicating that these proteins were not the luminal Ca(2+) sensor for the IP(3) receptor. Although Stim1(-/-) cells displayed a normal IP(3)-receptor function, agonist-induced Ca(2+) release was reduced. This finding suggests that the presence of STIM1 is required for proper agonist-induced Ca(2+) signaling. Our data do not provide experimental evidence for the suggestion that STIM proteins would directly control the function of the IP(3) receptor.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / antagonists & inhibitors
  • Calcium / physiology*
  • Calcium Channels
  • Calcium Signaling / genetics
  • Calcium Signaling / physiology*
  • Cells, Cultured
  • Endoplasmic Reticulum / genetics
  • Endoplasmic Reticulum / metabolism
  • Fibroblasts / metabolism*
  • Inositol 1,4,5-Trisphosphate / agonists
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Inositol 1,4,5-Trisphosphate Receptors / biosynthesis
  • Inositol 1,4,5-Trisphosphate Receptors / genetics
  • Inositol 1,4,5-Trisphosphate Receptors / physiology
  • Membrane Glycoproteins / agonists
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Knockout
  • Protein Isoforms / agonists
  • Protein Isoforms / deficiency
  • Protein Isoforms / physiology
  • Stromal Interaction Molecule 1
  • Stromal Interaction Molecule 2

Substances

  • Calcium Channels
  • Inositol 1,4,5-Trisphosphate Receptors
  • Membrane Glycoproteins
  • Protein Isoforms
  • Stim1 protein, mouse
  • Stim2 protein, mouse
  • Stromal Interaction Molecule 1
  • Stromal Interaction Molecule 2
  • Inositol 1,4,5-Trisphosphate
  • Calcium