The gamma secretase catalytic subunit presenilin 1 (PS1) is expressed in the endoplasmic reticulum (ER) of neurons, where it regulates Ca²⁺ signaling. PS1 is also expressed in heart, but its role in regulation of cardiac Ca²⁺ transport remains unknown. Since the type 2 sarco/endoplasmic reticulum Ca²⁺ ATPase (SERCA2a) plays a central role in cardiac Ca²⁺ homeostasis, we studied whether PS1 regulates the cardiac SERCA2a function. The experiments were conducted in an inducible human SERCA2a stable T-Rex-293 cell line transfected with fluorescently labeled PS1 and the ER Ca²⁺ sensor R-CEPIA1er. Confocal imaging showed that that PS1 is localized predominantly in the ER membrane. Fluorescent resonance energy transfer (FRET) experiments in HEK293 cells transfected with fluorescently labeled SERCA2a and PS1 revealed that the two proteins directly interact with a 1:1 stoichiometry. The functional significance of this interaction was investigated in a heterologous cellular environment using a novel approach to directly measure ER Ca²⁺ dynamics. Measurements of SERCA2a-mediated Ca²⁺ transport showed that PS1 enhanced Ca²⁺ uptake at low ER Ca²⁺ loads (<0.15 mM) and reduced uptake at high loads (>0.35 mM). The results of this study revealed that PS1 could act as an important regulator of the cardiac Ca²⁺ pump function with a complex stimulatory/inhibitory profile.

γ 分泌酶催化亚基早老素 1 (PS1) 在神经元的内质网 (ER) 中表达，它调节 Ca ²⁺信号传导。PS1 也在心脏中表达，但其在调节心脏 Ca ²⁺转运中的作用仍然未知。由于 2 型肉瘤/内质网 Ca ²⁺ ATP 酶 (SERCA2a) 在心脏 Ca ²⁺稳态中起核心作用，我们研究了 PS1 是否调节心脏 SERCA2a 功能。实验在用荧光标记的 PS1 和 ER Ca ^{2+转染的诱导型人 SERCA2a 稳定 T-Rex-293 细胞系中进行}传感器 R-CEPIA1er。共聚焦成像显示 PS1 主要位于 ER 膜中。在转染了荧光标记的 SERCA2a 和 PS1 的 HEK293 细胞中进行的荧光共振能量转移 (FRET) 实验表明，这两种蛋白质以 1:1 的化学计量比直接相互作用。^{使用一种直接测量ER Ca 2+}动力学的新方法在异源细胞环境中研究了这种相互作用的功能意义。SERCA2a 介导的 Ca ²⁺转运的测量结果表明，PS1在低 ER Ca ^{2+负载（<0.15 mM）下增强 Ca 2+}摄取，并在高负载（>0.35 mM）下减少摄取。这项研究的结果表明，PS1 可以作为心脏 Ca²⁺泵功能，具有复杂的刺激/抑制特性。