Please use this identifier to cite or link to this item: https://doi.org/10.4049/jimmunol.1001225
Title: Secreted M-ficolin anchors onto monocyte transmembrane G protein-coupled receptor 43 and cross talks with plasma C-reactive protein to mediate immune signaling and regulate host defense
Authors: Zhang, J.
Yang, L. 
Ang, Z.
Yoong, S.L.
Tran, T.T.T.
Srianand, G.N.
Tan, N.S.
Ho, B.
Ding, J.L. 
Issue Date: 1-Dec-2010
Citation: Zhang, J., Yang, L., Ang, Z., Yoong, S.L., Tran, T.T.T., Srianand, G.N., Tan, N.S., Ho, B., Ding, J.L. (2010-12-01). Secreted M-ficolin anchors onto monocyte transmembrane G protein-coupled receptor 43 and cross talks with plasma C-reactive protein to mediate immune signaling and regulate host defense. Journal of Immunology 185 (11) : 6899-6910. ScholarBank@NUS Repository. https://doi.org/10.4049/jimmunol.1001225
Abstract: Although transmembrane C-type lectins (CLs) are known to initiate immune signaling, the participation and mechanism of action of soluble CLs have remained enigmatic. In this study, we found that M-ficolin, a conserved soluble CL of monocyte origin, overcomes its lack of membrane-anchor domain by docking constitutively onto a monocyte transmembrane receptor, G protein-coupled receptor 43 (GPCR43), to form a pathogen sensor-cum-signal transducer. On encountering microbial invaders, the M-ficolin-GPCR43 complex activates the NF-κB cascade to upregulate IL-8 production. We showed that mild acidosis at the local site of infection induces conformational changes in the M-ficolin molecule, which provokes a strong interaction between the C-reactive protein (CRP) and the M-ficolin-GPCR43 complex. The collaboration among CRP-M-ficolin-GPCR43 under acidosis curtails IL-8 production thus preventing immune overactivation. Therefore, we propose that a soluble CL may become membraneassociated through interaction with a transmembrane protein, whereupon infection collaborates with other plasma protein to transduce the infection signal and regulate host defense. Our finding implies a possible mechanism whereby the host might expand its repertoire of immune recognition-cum- regulation tactics by promiscuous protein networking. Furthermore, our identification of the pH-sensitive interfaces of M-ficolin-CRP provides a powerful template for future design of potential immunomodulators. Copyright © 2010 by The American Association of Immunologists, Inc.
Source Title: Journal of Immunology
URI: http://scholarbank.nus.edu.sg/handle/10635/114386
ISSN: 00221767
DOI: 10.4049/jimmunol.1001225
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