title: A CD46-like molecule functional in teleost fish represents an ancestral form of membrane-bound regulators of complement activation.
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.
authors.affiliation: Laboratory of Marine Biochemistry, Department of Bioscience and Biotechnology, Kyushu University, Hakozaki, Fukuoka 812-8581, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Tsujikura
authors.affiliation: Laboratory of Marine Biochemistry, Department of Bioscience and Biotechnology, Kyushu University, Hakozaki, Fukuoka 812-8581, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nagasawa
authors.affiliation: Laboratory of Marine Biochemistry, Department of Bioscience and Biotechnology, Kyushu University, Hakozaki, Fukuoka 812-8581, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Ichiki
authors.affiliation: Laboratory of Marine Biochemistry, Department of Bioscience and Biotechnology, Kyushu University, Hakozaki, Fukuoka 812-8581, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Nakamura
authors.affiliation: Laboratory of Marine Biochemistry, Department of Bioscience and Biotechnology, Kyushu University, Hakozaki, Fukuoka 812-8581, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Somamoto
authors.affiliation: Laboratory of Marine Biochemistry, Department of Bioscience and Biotechnology, Kyushu University, Hakozaki, Fukuoka 812-8581, Japan mikimnakao@kyudai.jp.
authors.forename: Miki
authors.initials: M
authors.lastname: Nakao
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001483:Base Sequence; D016466:CHO Cells; D002347:Carps / Q000276:immunology*; D002460:Cell Line; D003001:Cloning, Molecular; D003167:Complement Activation / Q000276:immunology*; D003176:Complement C3 / Q000235:genetics* / Q000276:immunology; D003181:Complement C4 / Q000235:genetics* / Q000276:immunology; D006224:Cricetinae; D003412:Cricetulus; D004912:Erythrocytes / Q000276:immunology; D015870:Gene Expression; D051916:Membrane Cofactor Protein / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000096:biosynthesis; D017422:Sequence Analysis, DNA; D015027:Zebrafish / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D003176:Complement C3; D003181:Complement C4; D051916:Membrane Cofactor Protein; D020033:Protein Isoforms; D012333:RNA, Messenger