Plasma membrane Ca2+ ATPases as dynamic regulators of cellular calcium handling
Plasma membrane Ca2+ ATPases as dynamic regulators of cellular calcium handling
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DOI：
10.1196/annals.1387.023
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发表时间：
2007-01-01
期刊：
影响因子：
--
通讯作者：
Enyedi, Agnes
中科院分区：
文献类型：
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作者：
Strehler, Emanuel E.;Caride, Ariel J.;Enyedi, Agnes
质膜Ca~(2+)-ATPase(PMCA)是调节和微调细胞内Ca~(2+)浓度的细胞工具箱的重要组成部分。从历史上看，PMCA在维持细胞内钙动态平衡方面扮演着看家的角色。最近的工作揭示了大量令人困惑的PMCA异构体和选择性剪接变异体，提出了它们在不同钙负荷条件下在钙处理中的具体作用的问题。对单个异构体的动力学研究，结合表达和定位研究表明，PMCA根据组织和细胞的特定需求优化了钙调节功能。不同的PMCA亚型有助于控制某些细胞中缓慢而紧张性的钙信号，以及其他细胞中快速、有效的钙排出。局部的钙离子处理需要将泵定位于特定的细胞位置，如耳蜗毛细胞的顶膜或肾上皮细胞的基侧膜。最近的研究表明，PMCA中的选择性剪接区负责其独特的靶向、膜定位和信号串扰。PMCA的受控部署和从特定膜上的回收为细胞提供了一个动态系统，以响应不断变化的钙调节需求。
Plasma membrane Ca2+ ATPases (PMCAs) are essential components of the cellular toolkit to regulate and fine-tune cytosolic Ca2+ concentrations. Historically, the PMCAs have been assigned a housekeeping role in the maintenance of intracellular Ca2+ homeostasis. More recent work has revealed a perplexing multitude of PMCA isoforms and alternative splice variants, raising questions about their specific role in Ca2+ handling under conditions of varying Ca2+ loads. Studies on the kinetics of individual isoforms, combined with expression and localization studies suggest that PMCAs are optimized to function in Ca2+ regulation according to tissue- and cell-specific demands. Different PMCA isoforms help control slow, tonic Ca2+ signals in some cells and rapid, efficient Ca2+ extrusion in others. Localized Ca2+ handling requires targeting of the pumps to specialized cellular locales, such as the apical membrane of cochlear hair cells or the basolateral membrane of kidney epithelial cells. Recent studies suggest that alternatively spliced regions in the PMCAs are responsible for their unique targeting, membrane localization, and signaling cross-talk. The regulated deployment and retrieval of PMCAs from specific membranes provide a dynamic system for a cell to respond to changing needs of Ca2+ regulation.