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Human membrane cofactor protein (MCP, CD46): multiple isoforms and functions
T Seya1, A Hirano, M Matsumoto
1Department of Immunology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan. tseya@takaipro.jst.go.jp
Abstract:
Human membrane cofactor protein (MCP, CD46) is a 45-70 kDa protein with genetic and tissue-specific heterogeneity, and is expressed on all nucleated cells. MCP consists from N-terminus of 4 short consensus repeats (SCRs), 1-3 serine/threonine-rich (ST) domains, a transmembrane domain (TM) and a cytoplasmic tail (CYT). More than 8 isoforms are generated secondary to alternative splicing due to combinations of various exons encoding the ST, TM and CYT domains. It serves as a cofactor of serine protease factor I for inactivation of complement C3b and C4b. Its primary role is to protect host cells from homologous complement attack by inactivating C3b/C4b deposited on the membrane. It also acts as receptors for measles virus (MV), some kinds of bacteria and for a putative ligand on oocytes. MV infection causes temporal host immune suppression, which may appear secondary to signaling events through MCP on macrophages and dendritic cells. These functional properties of human MCP may facilitate xenotransplantation and may be useful in the generation of animal models of measles by creating human MCP-expressing animals.
Insights
Human membrane cofactor protein (MCP, CD46) protects cells from complement attack and serves as a receptor for measles virus. Its functions may aid xenotransplantation and measles research in animal models.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Human membrane cofactor protein (MCP, CD46) is a heterogeneous protein expressed on nucleated cells.
- MCP comprises SCRs, ST domains, a transmembrane domain, and a cytoplasmic tail, with over 8 isoforms generated by alternative splicing.
- It functions as a cofactor for Factor I in complement inactivation and acts as a receptor for pathogens and oocyte ligands.
Purpose of the Study:
- To detail the structure and function of human MCP (CD46).
- To explore the role of MCP in host defense and pathogen interactions.
- To highlight the potential applications of MCP in xenotransplantation and animal models for measles research.
Main Methods:
- Structural analysis of MCP domains (SCRs, ST, TM, CYT).
- Functional assays investigating MCP's role in complement regulation.
- Investigation of MCP as a receptor for measles virus and other agents.
Main Results:
- MCP's primary role is protecting host cells from complement-mediated damage by inactivating C3b/C4b.
- MCP mediates interactions with measles virus, bacteria, and oocyte ligands.
- Measles virus infection via MCP may lead to immune suppression, potentially through signaling in immune cells.
Conclusions:
- Human MCP (CD46) is a multifunctional protein critical for immune regulation and host-pathogen interactions.
- Its properties suggest significant potential for advancing xenotransplantation strategies.
- MCP's role in measles virus infection provides a basis for developing novel animal models for disease research.