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

作者：Duan, Qingrui; Zhang, Qingxi; Nie, Kun; Huang, Rui; Yang, Jianhua; He, Peikun; Tie, Zihui; Huang, Haifeng; Ma, Guixian; Zhang, Yuhu; Gao, Yuyuan^*; Wang, Lijuan^*

来源：iScience, 2023, 26(8): 107458.

DOI：10.1016/j.isci.2023.107458

• MOLECULAR-BASIS
• TRANSPORT
• JUNCTIONS
• MOTORS
• ACTIN

alpha-Synuclein preformed fibrils (alpha-syn PFF) in the blood can cross the blood-brain barrier and invade the central nervous system. Our previous study proved that alpha-syn PFF can be taken up by brain microvascular endothelial cells (BMVECs). Here, we found that alpha-syn PFF spread from BMVECs to pericytes with the highest transmission efficiency. We observed abundant tunneling nanotubes (TNTs) connecting BMVECs and pericytes, and alpha-syn PFF transmitted through these TNTs. Furthermore, alpha-syn PFF accumulation in BMVECs did not promote TNT formation, but activated the molecular motor Myo1d. Inhibition of Myo1d prevented alpha-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 alpha-syn PFF spread from BMVECs to pericytes through a mechanism involving TNTs and myosin. Targeting Myo1d may be a promising approach to prevent alpha-syn spreading from the blood to the brain.

• 单位
  南方医科大学; 广东省人民医院