Neuropilin-1 Acts as a Receptor for Complement Split Products
Claire Battin1, Annika De Sousa Linhares1, Wolfgang Paster1,2
1Division of Immune Receptors and T Cell Activation, Center for Pathophysiology, Infectiology, and Immunology, Institute of Immunology, Medical University of Vienna, Vienna, Austria.
Frontiers in Immunology
|October 2, 2019
Summary
Researchers discovered neuropilin-1 (NRP1) as a novel receptor for complement split products (CSPs) like C4d and C3d. Unlike other known receptors, NRP1 binds to CSPs covalently deposited on surfaces during complement activation, opening new avenues for understanding immune responses.
Area of Science:
- Immunology
- Molecular Biology
- Biochemistry
Background:
- Complement split products (CSPs), such as C4d and C3d, are key indicators of disease activity in autoimmunity and graft rejection.
- Existing research shows immunoglobulin-like transcript 4 (ILT4) interacts with soluble CSPs but not surface-bound ones.
Purpose of the Study:
- To identify novel cellular receptors that bind to covalently deposited CSPs.
- To investigate the interaction between neuropilin-1 (NRP1) and CSPs.
Main Methods:
- Utilized an unbiased screening approach with a cDNA mammalian expression library from human monocyte-derived dendritic cells.
- Probed the library with recombinant human C4d to identify interacting proteins.
- Characterized the binding kinetics and mapped the binding site of CSPs on NRP1.
Main Results:
- Identified neuropilin-1 (NRP1) as a novel receptor for C4d, C3d, and iC3b.
- Demonstrated that NRP1 binds to covalently surface-deposited CSPs, unlike ILT4.
- Determined a dose-dependent and saturable binding of C4d to NRP1 with a KD of 0.71 μM.
- Mapped the CSP binding site to the b1 domain of NRP1's coagulation factor V/VIII homology domain.
Conclusions:
- Neuropilin-1 (NRP1) functions as a novel classical complement receptor for surface-bound CSPs.
- This discovery reveals a new role for NRP1 in the complement system.
- Further research is needed to explore the functional implications of NRP1-CSP interactions in immunity.
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