Calcium ions (Ca2+) are prominent cell signaling effectors that regulate a wide variety of cellular processes. Among the different players in Ca2+ homeostasis, primary active Ca2+ transporters are responsible for keeping low basal Ca2+ levels in the cytosol while establishing steep Ca2+ gradients across intracellular membranes or the plasma membrane. This review summarizes our current knowledge on the three types of primary active Ca2+-ATPases: the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) pumps, the secretory pathway Ca2+- ATPase (SPCA) isoforms, and the plasma membrane Ca2+-ATPase (PMCA) Ca2+-transporters. We first discuss the Ca2+ transport mechanism of SERCA1a, which serves as a reference to describe the Ca2+ transport of other Ca2+ pumps. We further highlight the common and unique features of each isoform and review their structure-function relationship, expression pattern, regulatory mechanisms, and specific physiological roles. Finally, we discuss the increasing genetic and in vivo evidence that links the dysfunction of specific Ca2+-ATPase isoforms to a broad range of human pathologies, and highlight emerging therapeutic strategies that target Ca2+ pumps.

中文翻译：

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健康和疾病中的主要活性 Ca2+ 运输系统。

钙离子 (Ca2+) 是重要的细胞信号传导效应物，可调节多种细胞过程。在 Ca2+ 稳态的不同参与者中，主要的活性 Ca2+ 转运蛋白负责在细胞质中保持较低的基础 Ca2+ 水平，同时在细胞内膜或质膜上建立陡峭的 Ca2+ 梯度。这篇综述总结了我们目前对三种主要活性 Ca2+-ATP 酶的认识：肌（内）质网 Ca2+-ATP 酶（SERCA）泵、分泌途径 Ca2+-ATP 酶（SPCA）亚型和质膜 Ca2+-ATP 酶(PMCA) Ca2+-转运蛋白。我们首先讨论 SERCA1a 的 Ca2+ 转运机制，作为描述其他 Ca2+ 泵的 Ca2+ 转运的参考。我们进一步强调了每种亚型的共同和独特特征，并回顾了它们的结构-功能关系、表达模式、调节机制和特定的生理作用。最后，我们讨论了越来越多的遗传和体内证据，这些证据将特定 Ca2+-ATPase 异构体的功能障碍与广泛的人类病理联系起来，并强调了针对 Ca2+ 泵的新兴治疗策略。