Re-evaluation of the Role of Calcium Homeostasis Endoplasmic Reticulum Protein (CHERP) in Cellular Calcium Signaling
Re-evaluation of the Role of Calcium Homeostasis Endoplasmic Reticulum Protein (CHERP) in Cellular Calcium Signaling
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DOI：
10.1074/jbc.m112.405761
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发表时间：
2013-01-04
影响因子：
4.8
通讯作者：
Marchant, Jonathan S.
中科院分区：
文献类型：
--
作者：
Lin-Moshier, Yaping;Sebastian, Peter J.;Marchant, Jonathan S.
内质网内细胞内 Ca2+ 通道的激活导致细胞质 Ca2+ 浓度的变化，调节细胞生长和分化的多个方面。 Ca2+ 稳态内质网蛋白 (CHERP) 是一种普遍表达的蛋白质，已被提议作为内质网 Ca2+ 通道两个主要家族、肌醇 1,4,5-三磷酸受体 (IP(3)Rs) 和兰尼碱受体 (RyRs) 的调节剂，从而对有丝分裂周期产生影响。然而，CHERP 调节细胞内 Ca2+ 通道以影响细胞生长的方式尚不清楚。在此，我们对之前的研究结果提出质疑，即 CHERP 作为 IP(3)R 和 RyR 的直接细胞质调节剂，并提出 CHERP 在细胞核中发挥作用，通过调节 U2 snRNA 剪接体复合物的功能来影响细胞增殖。因此，之前报道的 CHERP 对细胞生长的影响可能是剪接体功能改变的间接影响，这与之前的数据一致，表明 U2 snRNP 成分功能丧失会干扰细胞生长并诱导细胞周期停滞。
Changes in cytoplasmic Ca2+ concentration, resulting from activation of intracellular Ca2+ channels within the endoplasmic reticulum, regulate several aspects of cellular growth and differentiation. Ca2+ homeostasis endoplasmic reticulum protein (CHERP) is a ubiquitously expressed protein that has been proposed as a regulator of both major families of endoplasmic reticulum Ca2+ channels, inositol 1,4,5-trisphosphate receptors (IP(3)Rs) and ryanodine receptors (RyRs), with resulting effects on mitotic cycling. However, the manner by which CHERP regulates intracellular Ca2+ channels to impact cellular growth is unknown. Here, we challenge previous findings that CHERP acts as a direct cytoplasmic regulator of IP(3)Rs and RyRs and propose that CHERP acts in the nucleus to impact cellular proliferation by regulating the function of the U2 snRNA spliceosomal complex. The previously reported effects of CHERP on cellular growth therefore are likely indirect effects of altered spliceosomal function, consistent with prior data showing that loss of function of U2 snRNP components can interfere with cell growth and induce cell cycle arrest.