C1q binds to apoptotic nucleolus and causes C1 protease degradation of nucleolar proteins [Cell Biology]
July 31st, 2015 by Cai, Y., Teo, B. H. D., Yeo, J. G., Lu, J.
In infections, 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-induced apoptosis, C1q initially bound to peripheral cellular regions in early apoptotic cells. By 6 hr, 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 C1 complex (C1qC1r2C1s2) and C1q binding to ligands activates the C1r/C1s proteases. Incubation of nucleoli with C1 caused degradation of nucleolar proteins neucleolin and nucleophosmin 1. This was inhibited by C1 inhibitor. The nucleoli are abundant with autoantigens. C1q binding and C1r/C1s degradation of nucleolar antigens during cell apoptosis potentially reduce autoimmunity. These findings help understand why genetic C1q and C1r/C1s deficiencies cause systemic lupus erythematosus.