STIM1, but not STIM2, is required for proper agonist-induced Ca2+ signaling.
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.
Decuypere
Jean-Paul
JP
Department of Molecular Cell Biology, Leuven, Belgium.
Monaco
Giovanni
G
Kiviluoto
Santeri
S
Oh-hora
Masatsugu
M
Luyten
Tomas
T
De Smedt
Humbert
H
Parys
Jan B
JB
Missiaen
Ludwig
L
Bultynck
Geert
G
D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000502:physiology*; D015220:Calcium Channels; D020013:Calcium Signaling / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000819:agonists / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D008562:Membrane Glycoproteins / Q000819:agonists / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D020033:Protein Isoforms / Q000819:agonists / Q000172:deficiency / Q000502:physiology; D000071737:Stromal Interaction Molecule 1; D000071738:Stromal Interaction Molecule 2
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008562:Membrane Glycoproteins; D020033:Protein Isoforms; C100757:Stim1 protein, mouse; C525024:Stim2 protein, mouse; D000071737:Stromal Interaction Molecule 1; D000071738:Stromal Interaction Molecule 2; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium