EFhd2 is a conserved calcium-binding protein that is highly expressed in the central nervous system. We have shown that EFhd2 interacts with tau protein, a key pathological hallmark in Alzheimer's disease and related dementias. However, EFhd2’s physiological and pathological functions in the brain are still poorly understood. To gain insights into its physiological function, we identified proteins that co-immunoprecipitated with EFhd2 from mouse forebrain and hindbrain, using tandem mass spectrometry (MS). In addition, quantitative mass spectrometry was used to detect protein abundance changes due to the deletion of the Efhd2 gene in mouse forebrain and hindbrain regions. Our data show that mouse EFhd2 is associated with cytoskeleton components, vesicle trafficking modulators, cellular stress response-regulating proteins, and metabolic proteins. Moreover, proteins associated with the cytoskeleton, vesicular transport, calcium signaling, stress response, and metabolic pathways showed differential abundance in Efhd2^(−/−) mice. This study presents, for the first time, an EFhd2 brain interactome that it is associated with different cellular and molecular processes. These findings will help prioritize further studies to investigate the mechanisms by which EFhd2 modulates these processes in physiological and pathological conditions of the nervous system.

中文翻译：

---

EFhd2 脑相互作用组揭示其与不同细胞和分子过程的关联

EFhd2 是一种保守的钙结合蛋白，在中枢神经系统中高度表达。我们已经证明 EFhd2 与 tau 蛋白相互作用，tau 蛋白是阿尔茨海默病和相关痴呆症的关键病理标志。然而，EFhd2 在大脑中的生理和病理功能仍知之甚少。为了深入了解其生理功能，我们使用串联质谱法 (MS) 鉴定了与来自小鼠前脑和后脑的 EFhd2 共免疫沉淀的蛋白质。此外，定量质谱用于检测由于Efhd2缺失引起的蛋白质丰度变化 小鼠前脑和后脑区域的基因。我们的数据显示小鼠 EFhd2 与细胞骨架成分、囊泡运输调节剂、细胞应激反应调节蛋白和代谢蛋白相关。此外，与细胞骨架、囊泡转运、钙信号、应激反应和代谢途径相关的蛋白质在 Efhd2 ^(−/−)小鼠中表现出差异丰度。这项研究首次提出了 EFhd2 大脑相互作用组，它与不同的细胞和分子过程相关。这些发现将有助于确定进一步研究的优先顺序，以研究 EFhd2 在神经系统的生理和病理条件下调节这些过程的机制。