中文版 | English
Title

Microglial debris is cleared by astrocytes via C4b-facilitated phagocytosis and degraded via RUBICON-dependent noncanonical autophagy in mice

Author
Corresponding AuthorPeng, Bo
Publication Years
2022-10-24
DOI
Source Title
EISSN
2041-1723
Volume13Issue:1
Abstract

Microglia are important immune cells in the central nervous system (CNS) that undergo turnover throughout the lifespan. If microglial debris is not removed in a timely manner, accumulated debris may influence CNS function. Clearance of microglial debris is crucial for CNS homeostasis. However, underlying mechanisms remain obscure. We here investigate how dead microglia are removed. We find that although microglia can phagocytose microglial debris in vitro, the territory-dependent competition hinders the microglia-to-microglial debris engulfment in vivo. In contrast, microglial debris is mainly phagocytosed by astrocytes in the brain, facilitated by C4b opsonization. The engulfed microglial fragments are then degraded in astrocytes via RUBICON-dependent LC3-associated phagocytosis (LAP), a form of noncanonical autophagy. Interference with C4b-mediated engulfment and subsequent LAP disrupt the removal and degradation of microglial debris, respectively. Together, we elucidate the cellular and molecular mechanisms of microglial debris removal in mice, extending the knowledge on the maintenance of CNS homeostasis.

URL[Source Record]
Indexed By
Language
English
Important Publications
NI Journal Papers
SUSTech Authorship
Others
Funding Project
National Outstanding Youth Science Fund Project of National Natural Science Foundation of China[32170958]
WOS Research Area
Science & Technology - Other Topics
WOS Subject
Multidisciplinary Sciences
WOS Accession No
WOS:000871563700004
Publisher
Scopus EID
2-s2.0-85140563371
Data Source
Scopus
Citation statistics
Cited Times [WOS]:4
Document TypeJournal Article
Identifierhttp://kc.sustech.edu.cn/handle/2SGJ60CL/407101
DepartmentDepartment of Biology
生命科学学院
Affiliation
1.Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen,Guangdong,518055,China
2.Department of Neurology,Jinshan Hospital,Institute for Translational Brain Research,State Key Laboratory of Medical Neurobiology,MOE Frontiers Center for Brain Science,Fudan University,Shanghai,201508,China
3.Department of Neurosurgery,Huashan Hospital,Fudan University,Shanghai,200040,China
4.Department of Orthopedics,The Third Affiliated Hospital of Jinzhou Medical University,Jinzhou,Liaoning,121012,China
5.Department of Laboratory Animal Science,MOE Frontiers Center for Brain Science,Fudan University,Shanghai,200032,China
6.Shanghai Key Laboratory of Psychotic Disorders,Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine,Shanghai,201108,China
7.Shanghai Frontiers Science Center of Genome Editing and Cell Therapy,Shanghai Key Laboratory of Regulatory Biology and School of Life Sciences,East China Normal University,Shanghai,200241,China
8.School of Life Sciences,Department of Biology,Shenzhen Key Laboratory of Gene Regulation and Systems Biology,Brain Research Center,Southern University of Science and Technology,Shenzhen,Guangdong,518055,China
9.Institute of Life Science,Nanchang University,Nanchang,Jiangxi,330031,China
10.Co-Innovation Center of Neuroregeneration,Nantong University,Nantong,Jiangsu,226001,China
Recommended Citation
GB/T 7714
Zhou, Tian,Li, Yuxin,Li, Xiaoyu,et al. Microglial debris is cleared by astrocytes via C4b-facilitated phagocytosis and degraded via RUBICON-dependent noncanonical autophagy in mice[J]. Nature Communications,2022,13(1).
APA
Zhou, Tian.,Li, Yuxin.,Li, Xiaoyu.,Zeng, Fanzhuo.,Rao, Yanxia.,...&Peng, Bo.(2022).Microglial debris is cleared by astrocytes via C4b-facilitated phagocytosis and degraded via RUBICON-dependent noncanonical autophagy in mice.Nature Communications,13(1).
MLA
Zhou, Tian,et al."Microglial debris is cleared by astrocytes via C4b-facilitated phagocytosis and degraded via RUBICON-dependent noncanonical autophagy in mice".Nature Communications 13.1(2022).
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