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由隧道纳米管介导的Tau蛋白和β-淀粉样蛋白的细胞间转运。

Intercellular transport of Tau protein and β-amyloid mediated by tunneling nanotubes.

作者信息

Zhang Kejia, Sun Zehui, Chen Xinyu, Zhang Yifan, Guo Angyang, Zhang Yan

机构信息

State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University Beijing 100871, China.

Duke Kunshan University Kunshan 215316, Jiangsu, China.

出版信息

Am J Transl Res. 2021 Nov 15;13(11):12509-12522. eCollection 2021.

Abstract

Tunneling nanotubes (TNTs) are thin channel-like structures connecting distant cells, providing a route for intercellular communication. In this study, we investigated the physical properties, including the cytoskeletal components, length and diameter, of the TNTs formed by HEK293T, U87 MG, and U251 cell lines. We found that organelles such as lysosomes, mitochondria, and Golgi bodies can be transported through TNTs, indicating that TNTs can mediate material transport. Moreover, we investigated the transport of the Tau protein and β-amyloid (Aβ), which are both closely related to Alzheimer's disease (AD) pathology, through TNTs. The results showed that TNTs formed by various neuronal cell lines can mediate the transport of different forms of the Tau protein and fluorescently labeled Aβ and that this transport is bidirectional, with different velocities in various cell lines. Our results confirmed the transport of the Tau protein and Aβ between cells and provided a possible explanation for the cascade of cell death in specific brain regions during the progression of AD. Our findings suggest new possibilities for the treatment of AD.

摘要

隧道纳米管(TNTs)是连接远距离细胞的薄通道样结构,为细胞间通讯提供了一条途径。在本研究中,我们调查了由HEK293T、U87 MG和U251细胞系形成的TNTs的物理特性,包括细胞骨架成分、长度和直径。我们发现,溶酶体、线粒体和高尔基体等细胞器可通过TNTs运输,这表明TNTs可介导物质运输。此外,我们研究了与阿尔茨海默病(AD)病理密切相关的 Tau 蛋白和β-淀粉样蛋白(Aβ)通过TNTs的运输。结果表明,由各种神经元细胞系形成的TNTs可介导不同形式的Tau蛋白和荧光标记的Aβ的运输,且这种运输是双向的,在各种细胞系中的速度不同。我们的结果证实了细胞间Tau蛋白和Aβ的运输,并为AD进展过程中特定脑区细胞死亡级联反应提供了一种可能的解释。我们的发现为AD的治疗提出了新的可能性。

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