title: C1q protein binds to the apoptotic nucleolus and causes C1 protease degradation of nucleolar proteins.
abstract: In infection, complement C1q recognizes pathogen-congregated antibodies and elicits complement activation. Among endogenous ligands, C1q binds to DNA and apoptotic cells, but whether C1q binds to nuclear DNA in apoptotic cells remains to be investigated. With UV irradiation-induced apoptosis, C1q initially bound to peripheral cellular regions in early apoptotic cells. By 6 h, binding concentrated in the nuclei to the nucleolus but not the chromatins. When nucleoli were isolated from non-apoptotic cells, C1q also bound to these structures. In vivo, C1q exists as the C1 complex (C1qC1r2C1s2), and C1q binding to ligands activates the C1r/C1s proteases. Incubation of nucleoli with C1 caused degradation of the nucleolar proteins nucleolin and nucleophosmin 1. This was inhibited by the C1 inhibitor. The nucleoli are abundant with autoantigens. C1q binding and C1r/C1s degradation of nucleolar antigens during cell apoptosis potentially reduces autoimmunity. These findings help us to understand why genetic C1q and C1r/C1s deficiencies cause systemic lupus erythematosus.
authors.affiliation: From the Department of Microbiology, Yong Loo Lin School of Medicine and Immunology Program, National University of Singapore, Singapore 117597.
authors.forename: Yitian
authors.initials: Y
authors.lastname: Cai
authors.affiliation: From the Department of Microbiology, Yong Loo Lin School of Medicine and Immunology Program, National University of Singapore, Singapore 117597.
authors.forename: Boon Heng Dennis
authors.initials: BH
authors.lastname: Teo
authors.affiliation: From the Department of Microbiology, Yong Loo Lin School of Medicine and Immunology Program, National University of Singapore, Singapore 117597.
authors.forename: Joo Guan
authors.initials: JG
authors.lastname: Yeo
authors.affiliation: From the Department of Microbiology, Yong Loo Lin School of Medicine and Immunology Program, National University of Singapore, Singapore 117597 miclujh@nus.edu.sg.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Lu
mesh_terms: D017209:Apoptosis / Q000528:radiation effects*; D002466:Cell Nucleolus / Q000378:metabolism*; D015922:Complement C1q / Q000378:metabolism*; D015923:Complement C1r / Q000378:metabolism*; D003173:Complement C1s / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D000090243:Nucleophosmin; D010750:Phosphoproteins / Q000378:metabolism*; D059748:Proteolysis / Q000528:radiation effects*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014466:Ultraviolet Rays; D000097796:Nucleolin
chemical_list: D015922:Complement C1q; D015923:Complement C1r; D003173:Complement C1s; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D000097796:Nucleolin; C000716967:NPM1 protein, human
keywords: C1q; C1s; apoptosis; autoimmunity; complement; dendritic cell; nucleolus