Calreticulin modulates capacitative Ca2+ influx by controlling the extent of inositol 1,4,5-trisphosphate-induced Ca2+ store depletion
Calreticulin modulates capacitative Ca2+ influx by controlling the extent of inositol 1,4,5-trisphosphate-induced Ca2+ store depletion
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DOI：
10.1074/jbc.m002041200
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发表时间：
2000-11-24
影响因子：
4.8
通讯作者：
DeLisle, S
中科院分区：
文献类型：
--
作者：
Xu, W;Longo, FJ;DeLisle, S
钙网蛋白（CRT）是一种高度保守的钙结合蛋白，存在于内质网（ER）的内腔。我们在非洲爪蟾卵母细胞中过表达CRT，以确定它如何调节1，4 -5-三磷酸肌醇（InsP（3））诱导的Ca 2+内流。在不影响因InsP（3）诱导的Ca 2+释放引起的胞质游离Ca 2+浓度（[Ca 2 +]（i））空间复杂升高的条件下，过表达的CRT使因Ca 2+内流引起的Ca 2+门控Cl-电流降低46%。缺失突变体显示CRT需要其高容量的Ca 2+结合结构域来降低由于Ca 2+内流引起的[Ca 2 +]（i）的升高。CRT也需要该功能域来减弱InsP（3）诱导的ER腔内游离Ca 2+浓度（[Ca 2 +]（ER））的下降，如“变色龙”指示剂所监测的。我们的数据表明，通过缓冲接近静息水平的[Ca 2 +]（ER），CRT可以防止InsP（3）耗尽细胞内储存足以激活Ca 2+内流。
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 (InsP(3))-induced Ca2+ influx. Under conditions where it did not affect the spatially complex elevations in free cytosolic Ca2+ concentration ([Ca2+](i)) due to InsP(3)-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 InsP(3)-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 InsP(3) from depleting the intracellular stores sufficiently to activate Ca2+ influx.