Institut National de la Santé et de la Recherche Médicale, Inserm UMR U978, UFR SMBH Université Paris 13-Paris Nord, 74, rue Marcel Cachin 93000 Bobigny, France.
Service d'Anatomie et Cytologie Pathologique, Hôpital Lariboisière, 1, rue Ambroise Paré, 75010 Paris, France.
Biomolecules. 2012 Mar 5;2(1):165-86. doi: 10.3390/biom2010165.
The endoplasmic reticulum (ER) is a major intracellular calcium storage pool and a multifunctional organelle that accomplishes several calcium-dependent functions involved in many homeostatic and signaling mechanisms. Calcium is accumulated in the ER by Sarco/Endoplasmic Reticulum Calcium ATPase (SERCA)-type calcium pumps. SERCA activity can determine ER calcium content available for intra-ER functions and for calcium release into the cytosol, and can shape the spatiotemporal characteristics of calcium signals. SERCA function therefore constitutes an important nodal point in the regulation of cellular calcium homeostasis and signaling, and can exert important effects on cell growth, differentiation and survival. In several cell types such as cells of hematopoietic origin, mammary, gastric and colonic epithelium, SERCA2 and SERCA3-type calcium pumps are simultaneously expressed, and SERCA3 expression levels undergo significant changes during cell differentiation, activation or immortalization. In addition, SERCA3 expression is decreased or lost in several tumor types when compared to the corresponding normal tissue. These observations indicate that ER calcium homeostasis is remodeled during cell differentiation, and may present defects due to decreased SERCA3 expression in tumors. Modulation of the state of differentiation of the ER reflected by SERCA3 expression constitutes an interesting new aspect of cell differentiation and tumor biology.
内质网（ER）是细胞内主要的钙储存池和多功能细胞器，完成了涉及多种内稳态和信号机制的几个依赖钙的功能。内质网中的钙是由肌浆/内质网钙 ATP 酶（SERCA）型钙泵积累的。SERCA 活性可以决定内质网中可用于内质网功能和向细胞质中释放钙的钙含量，并可以塑造钙信号的时空特征。因此，SERCA 功能构成了细胞内钙稳态和信号调节的重要节点，并对细胞生长、分化和存活产生重要影响。在几种细胞类型中，如造血细胞、乳腺、胃和结肠上皮细胞，同时表达 SERCA2 和 SERCA3 型钙泵，并且在细胞分化、激活或永生化过程中，SERCA3 的表达水平发生显著变化。此外，与相应的正常组织相比，在几种肿瘤类型中，SERCA3 的表达减少或丢失。这些观察结果表明，细胞分化过程中内质网钙稳态发生重构，并且由于肿瘤中 SERCA3 表达减少，可能存在缺陷。SERCA3 表达反映的内质网分化状态的调节构成了细胞分化和肿瘤生物学的一个有趣的新方面。
