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

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

iScience (Aug 2023)

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

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

Affiliations

Qingrui Duan: 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; Guangzhou Key Laboratory of Diagnosis and Treatment for Neurodegenerative Diseases, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China
Qingxi Zhang: Department of Neurology, Guangdong Neuroscience Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China; Guangzhou Key Laboratory of Diagnosis and Treatment for Neurodegenerative Diseases, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China
Kun Nie: Department of Neurology, Guangdong Neuroscience Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China; Guangzhou Key Laboratory of Diagnosis and Treatment for Neurodegenerative Diseases, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China
Rui Huang: Department of Neurology, Guangdong Neuroscience Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China; Guangzhou Key Laboratory of Diagnosis and Treatment for Neurodegenerative Diseases, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China
Jianhua Yang: Department of Neurology, Guangdong Neuroscience Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China; Guangzhou Key Laboratory of Diagnosis and Treatment for Neurodegenerative Diseases, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China
Peikun He: Department of Neurology, Guangdong Neuroscience Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China; Guangzhou Key Laboratory of Diagnosis and Treatment for Neurodegenerative Diseases, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China
Zihui Tie: Department of Neurology, Guangdong Neuroscience Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China; Guangzhou Key Laboratory of Diagnosis and Treatment for Neurodegenerative Diseases, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China
Haifeng Huang: Department of Neurology, Guangdong Neuroscience Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China; Guangzhou Key Laboratory of Diagnosis and Treatment for Neurodegenerative Diseases, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China
Guixian Ma: Department of Neurology, Guangdong Neuroscience Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China; Guangzhou Key Laboratory of Diagnosis and Treatment for Neurodegenerative Diseases, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China
Yuhu Zhang: Department of Neurology, Guangdong Neuroscience Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China; Guangzhou Key Laboratory of Diagnosis and Treatment for Neurodegenerative Diseases, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China
Yuyuan Gao: Department of Neurology, Guangdong Neuroscience Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China; Guangzhou Key Laboratory of Diagnosis and Treatment for Neurodegenerative Diseases, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China; Corresponding author
Lijuan Wang: 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; Guangzhou Key Laboratory of Diagnosis and Treatment for Neurodegenerative Diseases, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China; Corresponding author

Journal volume & issue: Vol. 26, no. 8
p. 107458

Abstract

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Summary: 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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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