Department of Cell and Chemical Biology, Leiden University Medical Center LUMC, Einthovenweg 20, 2300RC Leiden, The Netherlands.
Department of Cell and Chemical Biology, Leiden University Medical Center LUMC, Einthovenweg 20, 2300RC Leiden, The Netherlands
J Cell Sci. 2020 Dec 29;133(24):jcs249136. doi: 10.1242/jcs.249136.
Calcium is the third most abundant metal on earth, and the fundaments of its homeostasis date back to pre-eukaryotic life forms. In higher organisms, Ca serves as a cofactor for a wide array of (enzymatic) interactions in diverse cellular contexts and constitutes the most important signaling entity in excitable cells. To enable responsive behavior, cytosolic Ca concentrations are kept low through sequestration into organellar stores, particularly the endoplasmic reticulum (ER), but also mitochondria and lysosomes. Specific triggers are then used to instigate a local release of Ca on demand. Here, communication between organelles comes into play, which is accomplished through intimate yet dynamic contacts, termed membrane contact sites (MCSs). The field of MCS biology in relation to cellular Ca homeostasis has exploded in recent years. Taking advantage of this new wealth of knowledge, in this Review, we invite the reader on a journey of Ca flux through the ER and its associated MCSs. New mechanistic insights and technological advances inform the narrative on Ca acquisition and mobilization at these sites of communication between organelles, and guide the discussion of their consequences for cellular physiology.
钙是地球上含量第三丰富的金属，其体内平衡的基础可以追溯到原核生命形式。在高等生物中，钙作为许多（酶）相互作用的辅助因子存在于不同的细胞环境中，并构成可兴奋细胞中最重要的信号实体。为了实现响应性行为，通过将细胞质中的钙隔离到细胞器储存库中，特别是内质网（ER），但也包括线粒体和溶酶体，来保持低的细胞溶质钙浓度。然后，使用特定的触发因素按需引发局部钙释放。在这里，细胞器之间的通讯发挥作用，这是通过称为膜接触位点（MCS）的紧密但动态的接触来实现的。近年来，与细胞内钙稳态相关的 MCS 生物学领域取得了飞速发展。利用这些新知识，在这篇综述中，我们邀请读者踏上钙流经内质网及其相关 MCS 的旅程。新的机制见解和技术进步为这些细胞器间通讯位点的钙获取和动员提供了信息，并指导了对其对细胞生理学影响的讨论。
