Institut National de la Santé et de la Recherche Médicale, UMR U976, Institut Saint-Louis, 75010 Paris, France.
Institut de Recherche Saint-Louis, Hôpital Saint-Louis, Université de Paris, 75010 Paris, France.
Int J Mol Sci. 2020 May 9;21(9):3351. doi: 10.3390/ijms21093351.
Endoplasmic reticulum (ER) calcium homeostasis plays an essential role in cellular calcium signaling, intra-ER protein chaperoning and maturation, as well as in the interaction of the ER with other organelles. Calcium is accumulated in the ER by sarco/endoplasmic reticulum calcium ATPases (SERCA enzymes) that generate by active, ATP-dependent transport, a several thousand-fold calcium ion concentration gradient between the cytosol (low nanomolar) and the ER lumen (high micromolar). SERCA enzymes are coded by three genes that by alternative splicing give rise to several isoforms, which can display isoform-specific calcium transport characteristics. SERCA expression levels and isoenzyme composition vary according to cell type, and this constitutes a mechanism whereby ER calcium homeostasis is adapted to the signaling and metabolic needs of the cell, depending on its phenotype, its state of activation and differentiation. As reviewed here, in several normal epithelial cell types including bronchial, mammary, gastric, colonic and choroid plexus epithelium, as well as in mature cells of hematopoietic origin such as pumps are simultaneously expressed, whereas in corresponding tumors and leukemias SERCA3 expression is selectively down-regulated. SERCA3 expression is restored during the pharmacologically induced differentiation of various cancer and leukemia cell types. SERCA3 is a useful marker for the study of cell differentiation, and the loss of SERCA3 expression constitutes a previously unrecognized example of the remodeling of calcium homeostasis in tumors.
内质网（ER）钙稳态在细胞钙信号转导、内质网内蛋白伴侣和成熟以及 ER 与其他细胞器的相互作用中起着至关重要的作用。肌浆/内质网钙 ATP 酶（SERCA 酶）通过主动的、ATP 依赖性的运输将钙积累在内质网中，在细胞质（低纳摩尔）和内质网腔（高微摩尔）之间产生了几千倍的钙离子浓度梯度。SERCA 酶由三个基因编码，通过选择性剪接产生了几个同工型，这些同工型可以显示出同工型特异性的钙转运特性。SERCA 的表达水平和同工酶组成根据细胞类型而变化，这是一种机制，通过这种机制，内质网钙稳态可以根据细胞的表型、激活状态和分化来适应细胞的信号转导和代谢需求。正如这里所综述的，在几种正常的上皮细胞类型中，包括支气管、乳腺、胃、结肠和脉络丛上皮，以及造血来源的成熟细胞如泵，同时表达，而在相应的肿瘤和白血病中，SERCA3 的表达被选择性地下调。在各种癌症和白血病细胞类型的药理学诱导分化过程中，SERCA3 的表达得到恢复。SERCA3 是研究细胞分化的有用标志物，SERCA3 表达的丧失构成了肿瘤中钙稳态重塑的一个以前未被认识到的例子。
