肌球蛋白1d通过隧道纳米管促进α-突触核蛋白从脑微血管内皮细胞向周细胞的转移。
Myo1d promotes alpha-synuclein transfer from brain microvascular endothelial cells to pericytes through tunneling nanotubes.
作者信息
Duan Qingrui, Zhang Qingxi, Nie Kun, Huang Rui, Yang Jianhua, He Peikun, Tie Zihui, Huang Haifeng, Ma Guixian, Zhang Yuhu, Gao Yuyuan, Wang Lijuan
机构信息
School of Medicine, South China University of Technology, Guangzhou 510006, China.
Department of Neurology, Guangdong Neuroscience Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China.
出版信息
iScience. 2023 Jul 22;26(8):107458. doi: 10.1016/j.isci.2023.107458. eCollection 2023 Aug 18.
α-Synuclein preformed fibrils (α-syn PFF) in the blood can cross the blood-brain barrier and invade the central nervous system. Our previous study proved that α-syn PFF can be taken up by brain microvascular endothelial cells (BMVECs). Here, we found that α-syn PFF spread from BMVECs to pericytes with the highest transmission efficiency. We observed abundant tunneling nanotubes (TNTs) connecting BMVECs and pericytes, and α-syn PFF transmitted through these TNTs. Furthermore, α-syn PFF accumulation in BMVECs did not promote TNT formation, but activated the molecular motor Myo1d. Inhibition of Myo1d prevented α-syn PFF transfer from BMVECs to pericytes and decreased the colocalization of Myo1d and F-actin in BMVECs. In summary, we are the first to demonstrate that α-syn PFF spread from BMVECs to pericytes through a mechanism involving TNTs and myosin. Targeting Myo1d may be a promising approach to prevent α-syn spreading from the blood to the brain.
血液中的α-突触核蛋白原纤维（α-syn PFF）能够穿过血脑屏障并侵入中枢神经系统。我们之前的研究证明，α-syn PFF可被脑微血管内皮细胞（BMVECs）摄取。在此，我们发现α-syn PFF以最高的传播效率从BMVECs扩散至周细胞。我们观察到有大量的隧道纳米管（TNTs）连接着BMVECs和周细胞，且α-syn PFF通过这些TNTs进行传播。此外，α-syn PFF在BMVECs中的积累并未促进TNT的形成，而是激活了分子运动蛋白Myo1d。抑制Myo1d可阻止α-syn PFF从BMVECs转移至周细胞，并减少BMVECs中Myo1d与F-肌动蛋白的共定位。总之，我们首次证明α-syn PFF通过一种涉及TNTs和肌球蛋白的机制从BMVECs扩散至周细胞。靶向Myo1d可能是一种有前景的方法，可防止α-syn从血液扩散至大脑。
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