TY - JOUR
T1 - Calreticulin modulates capacitative Ca2+ influx by controlling the extent of inositol 1,4,5-trisphosphate-induced Ca2+ store depletion
AU - Xu, Wen
AU - Longo, Frank J.
AU - Wintermantel, Mary R.
AU - Jiang, Xueying
AU - Clark, Robert A.
AU - DeLisle, Sylvain
PY - 2000/11/24
Y1 - 2000/11/24
N2 - Calreticulin (CRT) is a highly conserved Ca2+-binding protein that resides in the lumen of the endoplasmic reticulum (ER). We overexpressed CRT in Xenopus oocytes to determine how it could modulate inositol 1,4,5-trisphosphate (InsP3)-induced Ca2+ influx. Under conditions where it did not affect the spatially complex elevations in free cytosolic Ca2+ concentration ([Ca2+](i)) due to InsP3-induced Ca2+ release, overexpressed CRT decreased by 46% the Ca2+-gated Cl- current due to Ca2+ influx. Deletion mutants revealed that CRT requires its high capacity Ca2+-binding domain to reduce the elevations of [Ca2+](i) due to Ca2+ influx. This functional domain was also required for CRT to attenuate the InsP3-induced decline in the free Ca2+ concentration within the ER lumen ([Ca2+](ER)), as monitored with a 'chameleon' indicator. Our data suggest that by buffering [Ca2+](ER) near resting levels, CRT may prevent InsP3 from depleting the intracellular stores sufficiently to activate Ca2+ influx.
AB - Calreticulin (CRT) is a highly conserved Ca2+-binding protein that resides in the lumen of the endoplasmic reticulum (ER). We overexpressed CRT in Xenopus oocytes to determine how it could modulate inositol 1,4,5-trisphosphate (InsP3)-induced Ca2+ influx. Under conditions where it did not affect the spatially complex elevations in free cytosolic Ca2+ concentration ([Ca2+](i)) due to InsP3-induced Ca2+ release, overexpressed CRT decreased by 46% the Ca2+-gated Cl- current due to Ca2+ influx. Deletion mutants revealed that CRT requires its high capacity Ca2+-binding domain to reduce the elevations of [Ca2+](i) due to Ca2+ influx. This functional domain was also required for CRT to attenuate the InsP3-induced decline in the free Ca2+ concentration within the ER lumen ([Ca2+](ER)), as monitored with a 'chameleon' indicator. Our data suggest that by buffering [Ca2+](ER) near resting levels, CRT may prevent InsP3 from depleting the intracellular stores sufficiently to activate Ca2+ influx.
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U2 - 10.1074/jbc.M002041200
DO - 10.1074/jbc.M002041200
M3 - Article
C2 - 10973951
AN - SCOPUS:0034711256
SN - 0021-9258
VL - 275
SP - 36676
EP - 36682
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 47
ER -