Abstract
BackgroundIn mammals, CEACAM1 and closely related members represent paired receptors with similar extracellular ligand-binding regions and cytoplasmic domains with opposing functions. Human CEACAM1 and CEACAM3 which have inhibitory ITIM/ITSM and activating ITAM-like motifs, respectively, in their cytoplasmic regions are such paired receptors. Various bacterial pathogens bind to CEACAM1 on epithelial and immune cells facilitating both entry into the host and down-regulation of the immune response whereas interaction with granulocyte-specific CEACAM3 leads to their uptake and destruction. It is unclear whether paired CEACAM receptors also exist in other vertebrate clades.ResultsWe identified more than 80 ceacam genes in Xenopus tropicalis and X. laevis. They consist of two subgroups containing one or two putative paired receptor pairs each. Analysis of genomic sequences of paired receptors provide evidence that their highly similar ligand binding domains were adjusted by recent gene conversion events. In contrast, selection for diversification is observed among inhibitory receptor orthologs of the two frogs which split some 60 million years ago. The allotetraploid X. laevis arose later by hybridization of two closely related species. Interestingly, despite the conservation of the genomic landscape surrounding the homeologous ceacam loci only one locus resembles the one found in X. tropicalis. From the second X. laevis locus more than 80 % of the ceacam genes were lost including 5 of the 6 paired receptor genes. This suggests that once the gene for one of the paired receptors is lost the remaining gene cluster degrades rapidly probably due to lack of selection pressure exerted by pathogens.ConclusionsThe presence of paired receptors and selection for diversification suggests that also in amphibians CEACAM1-related inhibitory proteins are or were used as pathogen receptors.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3279-9) contains supplementary material, which is available to authorized users.
Highlights
In mammals, CEACAM1 and closely related members represent paired receptors with similar extracellular ligand-binding regions and cytoplasmic domains with opposing functions
A number of bacterial pathogens like pathogenic Neisseria (N. gonorrhoeae, N. meningitis) Haemophilus influenzae and Moraxella catarrhalis have been shown to bind to the N-terminal immunoglobulin (Ig) variable-like domain of CEACAM1 on epithelial and immune cells allowing both entry into the host by transcytosis and downregulation of the host’s immune response by inhibiting adaptive and innate immune reactions [5,6,7,8,9,10,11]
Identification of ceacam gene families in X. tropicalis and X. laevis Based on their syntenic location between the flanking genes lipe and bcl3, and the presence of exons with conserved phasing encoding Ig variable (IgV)- and Ig constant (IgC)-like domains and Immunoreceptor tyrosine-based inhibition motif (ITIM) and Immunoreceptor tyrosine-based activation motif (ITAM)-like motifs most similar to mammalian CEACAM members (Fig. 1 and Additional file 1) 44 and 38 ceacam genes were identified on chromosomes 7 in X. tropicalis and X. laevis, respectively (Additional files 2 and 3)
Summary
CEACAM1 and closely related members represent paired receptors with similar extracellular ligand-binding regions and cytoplasmic domains with opposing functions. Various bacterial pathogens bind to CEACAM1 on epithelial and immune cells facilitating both entry into the host and down-regulation of the immune response whereas interaction with granulocyte-specific CEACAM3 leads to their uptake and destruction. It is unclear whether paired CEACAM receptors exist in other vertebrate clades. Other paired receptors directly interact with viral or bacterial pathogens [1] Among those are SIRPα and CEACAM1 and CEACAM3, members of the human carcinoembryonic antigen-related cell-cell adhesion molecule (CEACAM) family which have inhibitory ITIM/ ITSM motifs and activating ITAM-like motifs in their cytoplasmic regions, respectively [3, 4]. Phylogenetically unrelated adhesins such as opacityassociated (Opa) protein, outer membrane protein P5 and ubiquitous surface protein (UspA1) mediate interaction with the pathogen receptor CEACAM1 indicating convergent evolution [17,18,19]
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