title: Megf10 Is a Receptor for C1Q That Mediates Clearance of Apoptotic Cells by Astrocytes.
abstract: Multiple EGF-like domains 10 (Megf10) is a class F scavenger receptor (SR-F3) expressed on astrocytes and myosatellite cells, and recessive mutations in humans result in early-onset myopathy, areflexia, respiratory distress, and dysphagia (EMARDD). Here we report that Megf10-deficient mice have increased apoptotic cells in the developing cerebellum and have impaired phagocytosis of apoptotic cells by astrocytes ex vivo We also report that cells transfected with Megf10 gain the ability to phagocytose apoptotic neurons and that Megf10 binds with high affinity to C1q, an eat-me signal for apoptotic cells. In contrast, cells expressing Megf10 with EMARDD mutations have impaired apoptotic cell clearance and impaired binding to C1q. Our studies reveal that Megf10 is a receptor for C1q and identify a novel role for Megf10 in clearance of apoptotic cells in the mammalian developing brain with potential relevance to EMARDD patients and other CNS disorders.
  
  
  
  Apoptosis is a universal homeostatic process and occurs in many disease conditions. Multiple EGF-like domains 10 (Megf10) is emerging as an essential receptor for synaptic pruning, clearance of neuronal debris, and for muscle differentiation. Here we define a novel Megf10-dependent pathway for apoptotic cell clearance and show that Megf10 is a receptor for C1q, an eat-me signal, that binds phosphatidylserine expressed on the surface of apoptotic cells. Understanding the pathways by which apoptotic cells are cleared in the CNS is relevant to many physiological and pathological conditions of the CNS.
authors.affiliation: Center for Immunology and Inflammatory Diseases and Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, Sagol School of Neuroscience and Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel 69978, and.
authors.forename: Tal
authors.initials: T
authors.lastname: Iram
authors.affiliation: Center for Immunology and Inflammatory Diseases and Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114.
authors.forename: Zaida
authors.initials: Z
authors.lastname: Ramirez-Ortiz
authors.affiliation: Center for Immunology and Inflammatory Diseases and Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Byrne
authors.affiliation: Center for Immunology and Inflammatory Diseases and Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114.
authors.forename: Uwanda A
authors.initials: UA
authors.lastname: Coleman
authors.affiliation: Center for Immunology and Inflammatory Diseases and Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114.
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Kingery
authors.affiliation: Center for Immunology and Inflammatory Diseases and Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114.
authors.forename: Terry K
authors.initials: TK
authors.lastname: Means
authors.affiliation: Sagol School of Neuroscience and Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel 69978, and.
authors.forename: Dan
authors.initials: D
authors.lastname: Frenkel
authors.affiliation: Center for Immunology and Inflammatory Diseases and Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts 02114 jelkhoury@mgh.harvard.edu.
authors.forename: Joseph
authors.initials: J
authors.lastname: El Khoury
mesh_terms: D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000378:metabolism*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D015922:Complement C1q / Q000378:metabolism*; D049310:Distal Myopathies / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D010587:Phagocytosis; D011485:Protein Binding
chemical_list: C525222:Megf10 protein, mouse; D008565:Membrane Proteins; D015922:Complement C1q
keywords: C1q; EMARDD; MEGF10; apoptosis; astrocytes; clearance; scavenger receptor, SR-F3