Of the many crucial functions of the ER, homeostasis of physiological calcium increase is critical for signaling. Plasma membrane (PM) injury causes a pathological calcium influx. Here, we show that the ER helps clear this surge in cytoplasmic calcium through an ER-resident calcium pump, SERCA, and a calcium-activated ion channel, Anoctamin 5 (ANO5). SERCA imports calcium into the ER, and ANO5 supports this by maintaining electroneutrality of the ER lumen through anion import. Preventing either of these transporter activities causes cytosolic calcium overload and disrupts PM repair (PMR). ANO5 deficit in limb girdle muscular dystrophy 2L (LGMD2L) patient cells compromises their cytosolic and ER calcium homeostasis. By generating a mouse model of LGMD2L, we find that PM injury causes cytosolic calcium overload and compromises the ability of ANO5-deficient myofibers to repair. Addressing calcium overload in ANO5-deficient myofibers enables them to repair, supporting the requirement of the ER in calcium homeostasis in injured cells and facilitating PMR.

中文翻译：

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内质网维持质膜修复所需的离子稳态。

在ER的许多关键功能中，生理性钙增加的体内平衡对于信号传递至关重要。质膜（PM）损伤导致病理性钙内流。在这里，我们表明ER通过驻留于ER的钙泵SERCA和钙激活的离子通道Anoctamin 5（ANO5）有助于清除细胞质钙的这种激增。SERCA将钙导入ER，而ANO5通过阴离子导入维持ER管腔的电中性来支持这一点。阻止这些转运蛋白活动之一会导致胞质钙超载并破坏PM修复（PMR）。肢带肌营养不良症2L（LGMD2L）患者细胞中的ANO5缺乏症会损害其胞质和ER钙稳态。通过生成LGMD2L的鼠标模型，我们发现，PM损伤会引起胞质钙超载，并损害缺乏ANO5的肌纤维的修复能力。解决ANO5缺乏的肌纤维中的钙超载使他们能够修复，从而支持ER对受损细胞中钙稳态的需求，并促进PMR。