The biosynthesis of C1q, the collagen-like and Fc-recognizing molecule of the complement system.
C1q, the collagen-like and Fc-recognizing component of the complement system, is mainly synthesized in macrophages and epithelial cells. Inhibitors of collagen biosynthesis, known to inhibit the post-translational hydroxylation of proline and lysine residues, were as effective in macrophages as inhibitors of C1q synthesis and secretion as has been described for collagen. This indicates that post-translational processing of C1q is dependent upon its collagen portions and triple helical formation within the cells. The macrophage-derived C1q is immuno- and physicochemically identical with serum C1q indicating that macrophages have to be considered as a major source for serum C1q. This was recently confirmed by Northern blot analysis using a cDNA probe for the B-chain of murine C1q. In contrast, an extremely weak signal was found in kidney, lung, gut, muscle and liver RNA. Besides the 11 S C1q molecule macrophages also synthesize a low molecular weight (LMW) form of C1q. The biological function of this 4 S LMW-C1q is still unclear. Macrophage-derived and secreted C1q is reinserted into the macrophage membrane. It is unlikely that the membranous form of C1q is bound via C1q-receptors into the membrane of macrophages since the B-chain of membrane-associated C1q is structurally different to that of fluid-phase C1q. The demonstration of a distinct membrane form of C1q supports earlier functional studies which implicated C1q as a membrane-associated molecule with receptor functions for those molecules which also interact with fluid-phase C1q, such as polyanions, the Fc portions of immune complexes, and bacteria (LPS and outer membrane proteins, OMP).
Loos
M
M
Institute of Medical Microbiology, Johannes Gutenberg-University, Mainz, W.-Germany.
Martin
H
H
Petry
F
F
D000818:Animals; D015922:Complement C1q / Q000096:biosynthesis* / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008970:Molecular Weight; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology
D008565:Membrane Proteins; D011500:Protein Synthesis Inhibitors; D015922:Complement C1q