CD157-extracellular matrix proteins interactions enhance integrin-mediated signalling cascade in monocytes.
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1
University of Torino, Department of Medical Sciences, Italy
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2
University of Camerino, School of Biosciences and Biotechnology, Italy
CD157 is a GPI-anchored ectoenzyme belonging to the NADase/ADP-ribosyl cyclase gene family involved in the control of human neutrophils and monocytes adhesion, migration and diapedesis. We demonstrated that CD157 physically interacts with β1 and β2 integrins in monocytes and its cross-linking by means of a monoclonal antibody (mimicking the natural ligand) recruits integrins to lipid rafts, promoting the transduction of optimal intracellular signals converging on the MAPK and PI3K pathways.
Here, we demonstrate that CD157 binds selected extracellular matrix proteins. Using solid phase binding assays and surface plasmon resonance analysis, we found that human recombinant CD157 binds to fibronectin, fibrinogen, laminin and collagen type I but not to vitronectin or to the polysaccharide components of extracellular matrix (such as heparin and hyaluronan). CD157 binding is concentration-dependent and is prevented by selected anti-CD157 monoclonal antibodies. Using recombinant fibronectin fragments, CD157 binding sites were mapped within the N-terminal and C-terminal heparin binding regions of fibronectin, which lack integrin-binding motifs.
Co-immunoprecipitation experiments using monocytic THP-1 cell line confirmed that: i) CD157 physically associates with fibronectin and ii) CD157 binding to fibronectin is required for promoting the association between CD157 and integrins. We hypothesize that the simultaneous engagement of CD157 and integrins by distinct domains of fibronectin represents the physiological mechanism promoting the interaction between CD157 and integrins, leading to the optimal activation of the signalling cascade which controls crucial aspects of monocytes extravasation.
Keywords:
Monocytes,
Extracellular Matrix,
fibronectin,
Integrins,
intracellular signalling
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune receptors and signaling
Citation:
Morone
S,
Augeri
S,
Giacomino
A,
Parrotta
R,
Lo Buono
N,
Cuccioloni
M,
Ortolan
E and
Funaro
A
(2013). CD157-extracellular matrix proteins interactions enhance integrin-mediated signalling cascade in monocytes..
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00231
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Received:
12 Mar 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Ms. Simona Morone, University of Torino, Department of Medical Sciences, Torino, 10126, Italy, simona.morone@unito.it