EFhd2 brain interactome reveals its association with different cellular and molecular processes.

EFhd2 brain interactome reveals its association with different cellular and molecular processes.
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DOI:
10.1111/jnc.15517
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发表时间:
2021-12
影响因子:
4.7
通讯作者:
Vega, Irving E.
Vega, Irving E.
中科院分区:
医学2区
文献类型:
--
作者:
Soliman, Ahlam S.;Umstead, Andrew;Grabinski, Tessa;Kanaan, Nicholas M.;Lee, Andy;Ryan, John;Lamp, Jared;Vega, Irving E.

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EFhd 2是一种在中枢神经系统中高度表达的保守的钙结合蛋白。我们已经证明EFhd 2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,EFhd 2在大脑中的生理和病理功能仍然知之甚少。为了深入了解其生理功能,我们使用串联质谱法(MS)鉴定了与小鼠前脑和后脑EFhd 2共免疫沉淀的蛋白质。此外,定量质谱法被用来检测蛋白质丰度的变化,由于Efhd 2基因在小鼠前脑和后脑区域的缺失。我们的数据表明,小鼠EFhd 2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。此外,与细胞骨架、囊泡运输、钙信号传导、应激反应和代谢途径相关的蛋白质在Efhd 2(-/-)小鼠中表现出不同的丰度。这项研究首次提出了EFhd 2脑相互作用组,它与不同的细胞和分子过程有关。这些发现将有助于优先进行进一步的研究,以探讨EFhd 2在神经系统的生理和病理条件下调节这些过程的机制。
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.
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