TY - JOUR
T1 - Role of regulator of G protein signaling 2 (RGS2) in Ca2+ oscillations and adaptation of Ca2+ signaling to reduce excitability of RGS2-/- cells
AU - Wang, Xinhua
AU - Huang, Guojin
AU - Luo, Xiang
AU - Penninger, Josef M.
AU - Muallem, Shmuel
PY - 2004/10/1
Y1 - 2004/10/1
N2 - Regulators of G protein signaling (RGS) proteins accelerate the GTPase activity of Gα subunits to determine the duration of the stimulated state and control G protein-coupled receptor-mediated cell signaling. RGS2 is an RGS protein that shows preference toward Gαq. To better understand the role of RGS2 in Ca2+ signaling and Ca2+ oscillations, we characterized Ca2+ signaling in cells derived from RGS2 -/- mice. Deletion of RGS2 modified the kinetic of inositol 1,4,5-trisphosphate (IP3) production without affecting the peak level of IP3, but rather increased the steady-state level of IP 3 at all agonist concentrations. The increased steady-state level of IP3 led to an increased frequency of [Ca2+]i oscillations. The cells were adapted to deletion of RGS2 by reducing Ca 2+ signaling excitability. Reduced excitability was achieved by adaptation of all transporters to reduce Ca2+ influx into the cytosol. Thus, IP3 receptor 1 was down-regulated and IP3 receptor 3 was up-regulated in RGS2-/- cells to reduce the sensitivity for IP3 to release Ca2+ from the endoplasmic reticulum to the cytosol. Sarco/endoplasmic reticulum Ca2+ ATPase 2b was upregulated to more rapidly remove Ca2+ from the cytosol of RGS2-/- cells. Agonist-stimulated Ca2+ influx was reduced, and Ca2+ efflux by plasma membrane Ca2+ was up-regulated in RGS2-/- cells. The result of these adaptive mechanisms was the reduced excitability of Ca2+ signaling, as reflected by the markedly reduced response of RGS2-/- cells to changes in the endoplasmic reticulum Ca2+ load and to an increase in extracellular Ca 2+. These findings highlight the central role of RGS proteins in [Ca2+]i oscillations and reveal a prominent plasticity and adaptability of the Ca2+ signaling apparatus.
AB - Regulators of G protein signaling (RGS) proteins accelerate the GTPase activity of Gα subunits to determine the duration of the stimulated state and control G protein-coupled receptor-mediated cell signaling. RGS2 is an RGS protein that shows preference toward Gαq. To better understand the role of RGS2 in Ca2+ signaling and Ca2+ oscillations, we characterized Ca2+ signaling in cells derived from RGS2 -/- mice. Deletion of RGS2 modified the kinetic of inositol 1,4,5-trisphosphate (IP3) production without affecting the peak level of IP3, but rather increased the steady-state level of IP 3 at all agonist concentrations. The increased steady-state level of IP3 led to an increased frequency of [Ca2+]i oscillations. The cells were adapted to deletion of RGS2 by reducing Ca 2+ signaling excitability. Reduced excitability was achieved by adaptation of all transporters to reduce Ca2+ influx into the cytosol. Thus, IP3 receptor 1 was down-regulated and IP3 receptor 3 was up-regulated in RGS2-/- cells to reduce the sensitivity for IP3 to release Ca2+ from the endoplasmic reticulum to the cytosol. Sarco/endoplasmic reticulum Ca2+ ATPase 2b was upregulated to more rapidly remove Ca2+ from the cytosol of RGS2-/- cells. Agonist-stimulated Ca2+ influx was reduced, and Ca2+ efflux by plasma membrane Ca2+ was up-regulated in RGS2-/- cells. The result of these adaptive mechanisms was the reduced excitability of Ca2+ signaling, as reflected by the markedly reduced response of RGS2-/- cells to changes in the endoplasmic reticulum Ca2+ load and to an increase in extracellular Ca 2+. These findings highlight the central role of RGS proteins in [Ca2+]i oscillations and reveal a prominent plasticity and adaptability of the Ca2+ signaling apparatus.
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U2 - 10.1074/jbc.M406450200
DO - 10.1074/jbc.M406450200
M3 - Article
C2 - 15292238
AN - SCOPUS:4744342418
SN - 0021-9258
VL - 279
SP - 41642
EP - 41649
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 40
ER -