PUBLICATION
A CD46-Like Molecule Functional in Teleost Fish Represents an Ancestral Form of Membrane-Bound Regulators of Complement Activation
- Authors
- Tsujikura, M., Nagasawa, T., Ichiki, S., Nakamura, R., Somamoto, T., Nakao, M.
- ID
- ZDB-PUB-141203-41
- Date
- 2015
- Source
- Journal of immunology (Baltimore, Md. : 1950) 194(1): 262-72 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Cricetulus
- Complement Activation/immunology*
- Amino Acid Sequence
- Complement C4/genetics*
- Complement C4/immunology
- Gene Expression
- Cricetinae
- Animals
- Zebrafish/immunology
- Sequence Analysis, DNA
- Molecular Sequence Data
- Cloning, Molecular
- RNA, Messenger/biosynthesis
- CHO Cells
- Erythrocytes/immunology
- Membrane Cofactor Protein/genetics
- Membrane Cofactor Protein/immunology*
- Cell Line
- Carps/immunology*
- Protein Structure, Tertiary
- Complement C3/genetics*
- Complement C3/immunology
- Protein Isoforms/genetics
- Protein Isoforms/immunology
- Antibodies, Monoclonal/immunology
- Mice
- Mice, Inbred BALB C
- Base Sequence
- PubMed
- 25452563 Full text @ J. Immunol.
Citation
Tsujikura, M., Nagasawa, T., Ichiki, S., Nakamura, R., Somamoto, T., Nakao, M. (2015) A CD46-Like Molecule Functional in Teleost Fish Represents an Ancestral Form of Membrane-Bound Regulators of Complement Activation. Journal of immunology (Baltimore, Md. : 1950). 194(1):262-72.
Abstract
In the complement system, the regulators of complement activation (RCA) play crucial roles in controlling excessive complement activation and in protecting host cell from misdirected attack of complement. Several members of RCA family have been cloned from cyclostome and bony fish species and classified into soluble and membrane-bound type as in mammalian RCA factors. Complement-regulatory functions have been described only for soluble RCA of lamprey and barred sand bass; however, little is known on the biological function of the membrane-bound RCA proteins in the lower vertebrates. In this study, a membrane-bound RCA protein, designated teleost complement-regulatory membrane protein (Tecrem), was cloned and characterized for its complement-regulatory roles. Carp Tecrem, an ortholog of a zebrafish type 2 RCA, ZCR1, consists of four short consensus repeat modules, a serine/threonine/proline-rich domain, a transmembrane region, and a cytoplasmic domain, from the N terminus, as does mammalian CD46. Tecrem showed a ubiquitous mRNA expression in carp tissues, agreeing well with the putative regulatory role in complement activation. A recombinant Chinese hamster ovary cell line bearing carp Tecrem showed a significantly higher tolerance against lytic activity of carp complement and less deposition of C3-S, the major C3 isotypes acting on the target cell, than control Chinese hamster ovary (mock transfectant). Anti-Tecrem mAb enhanced the depositions of carp C3 and two C4 isotypes on autologous erythrocytes. Thus, the present findings provide the evidence of complement regulation by a membrane-bound group 2 RCA in bony fish, implying the host-cell protection is an evolutionarily conserved mechanism in regulation of the complement system.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping