Lectin pathway of bony fish complement: identification of two homologs of the mannose-binding lectin associated with MASP2 in the common carp (Cyprinus carpio).
The lectin pathway of complement is considered to be the most ancient complement pathway as inferred from identification of ancient homologs of mannose-binding lectin (MBL) and MBL-associated serine proteases (MASPs) in some invertebrates. MBL homologs with galactose selectivity and an MASP3-like sequence also occur in bony fish, linking the evolution of the lectin complement pathway from invertebrates to higher vertebrates. However, these cannot be considered authentic complement components until confirmatory functional evidence is obtained. Here, we report the isolation and characterization of two MBL homologs from a cyprinid teleost, the common carp, Cyprinus carpio. One, designated GalBL, corresponds to the MBL-like molecule with the galactose specificity. The other is an authentic MBL with mannose specificity. Both were found to associate with a serine protease that cleaves native human C4 into C4b but not C4i with a hydrolyzed thioester. Molecular cloning and phylogenetic analysis revealed this C4-activating protease to be carp MASP2, indicating that MASP2 arose before the emergence of bony fish. Database mining of MBL-like genes reveals that MBL and GalBL genes are arranged in tandem in the zebrafish genome and that both lectins are conserved in the distantly related puffer fish. These results imply that bony fish have developed a diverged set of MBL homologs that function in the lectin complement pathway.
Nakao
Miki
M
Laboratory of Marine Biochemistry, Department of Bioscience and Biotechnology, Kyushu University, Hakozaki, Fukuoka, Japan. miki_n@agr.kyushu-u.ac.jp
Kajiya
Takayuki
T
Sato
Yuho
Y
Somamoto
Tomonori
T
Kato-Unoki
Yoko
Y
Matsushita
Misao
M
Nakata
Munehiro
M
Fujita
Teizo
T
Yano
Tomoki
T
D000818:Animals; D002347:Carps; D003001:Cloning, Molecular; D003181:Complement C4 / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism*; D019143:Evolution, Molecular; D005690:Galactose; D006801:Humans; D037102:Lectins / Q000378:metabolism*; D008358:Mannose; D037601:Mannose-Binding Lectin / Q000302:isolation & purification / Q000378:metabolism*; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000378:metabolism*; D010802:Phylogeny
D003181:Complement C4; D037102:Lectins; D037601:Mannose-Binding Lectin; D003165:Complement System Proteins; D050606:Mannose-Binding Protein-Associated Serine Proteases; D008358:Mannose; D005690:Galactose