Institut National de la Santé et de la Recherche Médicale, Inserm UMR-S, Institut Universitaire d'Hématologie, Université Paris Diderot-Paris, France.
Biofactors. 2011 May-Jun;37(3):139-49. doi: 10.1002/biof.142. Epub 2011 Jun 14.
Endoplasmic reticulum calcium homeostasis is involved in a multitude of signaling, as well as "house-keeping" functions that control cell growth, differentiation or apoptosis in every human/eukaryotic cell. Calcium is actively accumulated in the endoplasmic reticulum by Sarco/Endoplasmic Reticulum Calcium transport ATPases (SERCA enzymes). SERCA-dependent calcium transport is the only calcium uptake mechanism in this organelle, and therefore the regulation of SERCA function by the cell constitutes a key mechanism to adjust calcium homeostasis in the endoplasmic reticulum depending on the cell type and its state of differentiation. The direct pharmacological modulation of SERCA activity affects cell differentiation and survival. SERCA expression levels can undergo significant changes during cell differentiation or tumorigenesis, leading to modified endoplasmic reticulum calcium storage. In several cell types such as cells of hematopoietic origin or various epithelial cells, two SERCA genes (SERCA2 and SERCA3) are simultaneously expressed. Expression levels of SERCA3, a lower calcium affinity calcium pump are highly variable. In several cell systems SERCA3 expression is selectively induced during differentiation, whereas during tumorigenesis and blastic transformation SERCA3 expression is decreased. These observations point at the existence of a cross-talk, via the regulation of SERCA3 levels, between endoplasmic reticulum calcium homeostasis and the control of cell differentiation, and show that endoplasmic reticulum calcium homeostasis itself can undergo remodeling during differentiation. The investigation of the anomalies of endoplasmic reticulum differentiation in tumor and leukemia cells may be useful for a better understanding of the contribution of calcium signaling to the establishment of malignant phenotypes.
内质网钙稳态参与多种信号转导，以及“管家”功能，控制细胞生长、分化或凋亡在每一个人类/真核细胞。钙是积极积累在内质网肌浆/内质网钙转运 ATP 酶（SERCA 酶）。SERCA 依赖的钙转运是唯一的钙摄取机制在这个细胞器，因此细胞的 SERCA 功能的调节构成了一个关键的机制，根据细胞类型和分化状态来调节内质网的钙稳态。SERCA 活性的直接药理调节影响细胞分化和存活。SERCA 表达水平在细胞分化或肿瘤发生过程中会发生显著变化，导致内质网钙储存的改变。在几种细胞类型中，如造血细胞或各种上皮细胞，同时表达两种 SERCA 基因（SERCA2 和 SERCA3）。SERCA3 的表达水平，一种较低的钙亲和力钙泵，变化很大。在几种细胞系统中，SERCA3 的表达在分化过程中是选择性诱导的，而在肿瘤发生和白血病转化过程中，SERCA3 的表达减少。这些观察结果表明，内质网钙稳态和细胞分化控制之间存在通过 SERCA3 水平调节的交叉对话，并且表明内质网钙稳态本身可以在分化过程中进行重塑。研究肿瘤和白血病细胞内质网分化的异常可能有助于更好地理解钙信号对恶性表型建立的贡献。
