The C1q receptors: Focus on gC1qR/p33 (C1qBP, p32, HABP-1)(1) Journal Article

Authors: Ghebrehiwet, B.; Geisbrecht, B. V.; Xu, X.; Savitt, A. G.; Peerschke, E. I. B.
Article Title: The C1q receptors: Focus on gC1qR/p33 (C1qBP, p32, HABP-1)(1)
Abstract: In the past several years, a number of C1q binding surface proteins or receptors have been described. This is not of course surprising considering the complexity of the C1q molecule and its ability to bind to a wide range of cellular and plasma proteins via both its collagen-like [cC1q] region and its heterotrimeric globular heads [gC1q] each of which in turn is capable of binding a specific ligand. However, while each of these “receptor” molecules undoubtedly plays a specific function within its restricted microenvironment, and therefore merits full attention, this review nonetheless, will singularly focus on the structure and function of gC1qR–a multi-functional and multi-compartmental protein, which plays an important role in inflammation, infection, and cancer. Although first identified as a receptor for C1q, gC1qR has been shown to bind to a plethora of proteins found in plasma, on the cell surface and on pathogenic microorganisms. The plasma proteins that bind to gC1qR are mostly blood coagulation proteins and include high molecular weight kininogen [HK], Factor XII [Hageman factor], fibrinogen, thrombin [FII], and multimeric vitronectin. This suggests that gC1qR can play an important role in modulating not only of fibrin formation, particularly at local sites of immune injury and/or inflammation, but by activating the kinin/kallikrein system, it is also able to generate, bradykinin, a powerful vasoactive peptide that is largely responsible for the swelling seen in angioedema. Another important function of gC1qR is in cancer, where it has been shown to play a role in tumor cell survival, growth and metastatic invasion by interacting with critical molecules in the tumor cell microenvironment including those of the complement system and kinin system. Finally, by virtue of its ability to interact with a growing list of pathogen-associated molecules, including bacterial and viral ligands, gC1qR is becoming recognized as an important pathogen recognition receptor [PRR]. Given the numerous roles it plays in a growing list of disease settings, gC1qR has now become a potential target for the development of monoclonal antibody-based and/or small molecule-based therapies. © 2019
Keywords: unclassified drug; review; flow cytometry; neoplasm; cell proliferation; gene targeting; gene expression; inflammation; protein binding; tumor suppressor gene; immune response; gamma interferon; atherosclerosis; cd4+ t lymphocyte; fluorescence microscopy; crystal structure; real time polymerase chain reaction; lymphocyte; monocyte chemotactic protein 1; fibrinogen; vitronectin; chromosomal localization; polyacrylamide gel electrophoresis; tumor necrosis factor; angioneurotic edema; thrombin; tumor microenvironment; gel filtration; complement receptor; ionic strength; human; complement component c1q; bradykinin receptor; bradykinin; isoelectric point; c1q receptors; blood clotting factor 12; receptor for the globular heads of c1q (gc1qr); complement component gc1q receptor; high molecular weight kininogen; capillary endothelial cell; fibrin formation
Journal Title: Seminars in Immunology
Volume: 45
ISSN: 1044-5323
Publisher: Academic Press Inc., Elsevier Science  
Date Published: 2019-10-01
Start Page: 101338
Language: English
DOI: 10.1016/j.smim.2019.101338
PUBMED: 31744753
PROVIDER: scopus
Notes: Review -- Export Date: 2 January 2020 -- Source: Scopus
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