Myo1d promotes alpha-synuclein transfer from brain microvascular endothelial cells to pericytes through tunneling nanotubes

• Published in: iScience 2023-08, Vol.26 (8), p.107458-107458, Article 107458
• Main Authors: Duan, Qingrui, Zhang, Qingxi, Nie, Kun, Huang, Rui, Yang, Jianhua, He, Peikun, Tie, Zihui, Huang, Haifeng, Ma, Guixian, Zhang, Yuhu, Gao, Yuyuan, Wang, Lijuan
• Format: Article
• Language: English
• Subjects: Cellular neuroscience; Molecular neuroscience; Neuroscience; Omics; Transcriptomics
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.107458

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. [Display omitted] •The mechanisms of TNT and Myo1d for α-syn transfer BMVECs-pericytes is proposed•TNTs between BMVECs and pericytes are important for intercellular α-syn spreading•Target Myo1d may be an approach for preventing α-syn spreading BMVECs-pericytes Neuroscience; Molecular neuroscience; Cellular neuroscience; Omics; Transcriptomics