Characterization of C1q in teleosts: insight into the molecular and functional evolution of C1q family and classical pathway.
C1qs are key components of the classical complement pathway. They have been well documented in human and mammals, but little is known about their molecular and functional characteristics in fish. In the present study, full-length cDNAs of c1qA, c1qB, and c1qC from zebrafish (Danio rerio) were cloned, revealing the conservation of their chromosomal synteny and organization between zebrafish and other species. For functional analysis, the globular heads of C1qA (ghA), C1qB (ghB), and C1qC (ghC) were expressed in Escherichia coli as soluble proteins. Hemolytic inhibitory assays showed that hemolytic activity in carp serum can be inhibited significantly by anti-C1qA, -C1qB, and -C1qC of zebrafish, respectively, indicating that C1qA, C1qB, and C1qC are involved in the classical pathway and are conserved functionally from fish to human. Zebrafish C1qs also could specifically bind to heat-aggregated zebrafish IgM, human IgG, and IgM. The involvement of globular head modules in the C1q-dependent classical pathway demonstrates the structural and functional conservation of these molecules in the classical pathway and their IgM or IgG binding sites during evolution. Phylogenetic analysis revealed that c1qA, c1qB, and c1qC may be formed by duplications of a single copy of c1qB and that the C1q family is, evolutionarily, closely related to the Emu family. This study improves current understanding of the evolutionary history of the C1q family and C1q-mediated immunity.
Hu
Yu-Lan
YL
College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
Pan
Xin-Min
XM
Xiang
Li-Xin
LX
Shao
Jian-Zhong
JZ
D000818:Animals; D015922:Complement C1q / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003171:Complement Pathway, Classical / Q000502:physiology*; D004926:Escherichia coli; D019143:Evolution, Molecular; D006461:Hemolysis; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007075:Immunoglobulin M / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010802:Phylogeny; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011994:Recombinant Proteins; D029961:Zebrafish Proteins; D015922:Complement C1q