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Microglial debris is cleared by astrocytes via C4b-facilitated phagocytosis and degraded via RUBICON-dependent noncanonical autophagy in mice.
Zhou, Tian; Li, Yuxin; Li, Xiaoyu; Zeng, Fanzhuo; Rao, Yanxia; He, Yang; Wang, Yafei; Liu, Meizhen; Li, Dali; Xu, Zhen; Zhou, Xin; Du, Siling; Niu, Fugui; Peng, Jiyun; Mei, Xifan; Ji, Sheng-Jian; Shu, Yousheng; Lu, Wei; Guo, Feifan; Wu, Tianzhun; Yuan, Ti-Fei; Mao, Ying; Peng, Bo.
Affiliation
  • Zhou T; Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, China.
  • Li Y; 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.
  • Li X; Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200040, China.
  • Zeng F; 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.
  • Rao Y; Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200040, China.
  • He Y; 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.
  • Wang Y; Department of Orthopedics, The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 121012, China.
  • Liu M; Department of Laboratory Animal Science, MOE Frontiers Center for Brain Science, Fudan University, Shanghai, 200032, China.
  • Li D; Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 201108, China.
  • Xu Z; 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.
  • Zhou X; Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200040, China.
  • Du S; 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.
  • Niu F; Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200040, China.
  • Peng J; 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.
  • Mei X; 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.
  • Ji SJ; Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, China.
  • Shu Y; 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.
  • Lu W; 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.
  • Guo F; Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 201108, China.
  • Wu T; 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.
  • Yuan TF; Institute of Life Science, Nanchang University, Nanchang, Jiangxi, 330031, China.
  • Mao Y; Department of Orthopedics, The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 121012, China.
  • Peng B; 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.
Nat Commun ; 13(1): 6233, 2022 10 24.
Article in En | MEDLINE | ID: mdl-36280666
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Astrocytes / Microglia Limits: Animals Language: En Journal: Nat Commun Year: 2022 Document type: Article
Fulltext
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Astrocytes / Microglia Limits: Animals Language: En Journal: Nat Commun Year: 2022 Document type: Article