Fibrinogen-bearing protein genes in the snail Biomphalaria glabrata: Characterization of two novel genes and expression studies during ontogenesis and trematode infection

Abstract

All fibrinogen (FBG)-bearing proteins documented to date in the freshwater snail Biomphalaria glabrata, the intermediate host of the human blood fluke Schistosoma mansoni, possess the same molecular structure; one or two immunoglobin superfamily (IgSF) domains at the N-terminus and a FBG domain at the C-terminus (named as FBG-related protein (FREP)). Here we report two novel genes that encode FBG-bearing proteins from B. glabrata. Different from all known FREPs, the first gene encodes a protein (657 amino acids (aa)) composed of a long N-terminal region with no sequence homology to any known protein, a middle epidermal growth factor (EGF) repeat region and a Cterminal FBG domain, designated FBG-related molecule (FReM). A differential expression at 2 days post exposure (dpe) to the trematode S. mansoni or Echinostoma paraensei has been found in the S. mansoni susceptible M line and resistant BS-90 snail strains. The second gene is a new member of the FREP family, designated FREP14, which encodes a 399 aa putative secreted protein. FREP14 is different from known FREPs in that it is encoded by a single locus and is not upregulated in early or late stage S. mansoni exposure, but is upregulated in late stage E. paraensei infection. Furthermore, gene expression during the snail's ontogenesis and at a late stage of trematode-infection (52 dpe) has been investigated in the two newly-identified genes (FReM and FREP14) described in this paper and five representative members of known FREPs (FREPs 2,3,4,12,and 13). A variety of expression patterns were observed, suggestive of functional diversity among the members of FBG-bearing proteins. Our findings further broaden our understanding of the diversity and function of the FBGbearing protein encoded genes in B. glabrata.

Correlating structure and function during the evolution of fibrinogen‐related domains

“…FReDs from the snail Biomphalaria glabrata have been extensively studied in the past, 13,[44][45][46] and our observations are mainly confirmatory. Neighboring domains have previously been found to be immunoglobulin domains and, in one case, a brace of EGF domains.…”

“…Neighboring domains have previously been found to be immunoglobulin domains and, in one case, a brace of EGF domains. 46 The lengths of these FRePs range from 372 to 756 residues. One of these (NCBI: AEO50747.1) has a connector domain (COG1196) that is also found in a Drosophila FReP (NCBI: NP_001104020) and is a likely ortholog.…”

“…12,13,[46][47][48]57,63,64 Chief among these are the ficolins. Although genes for ficolins have been found among the protochordates, notably they have not been found in fish.…”

Sequence variability of fibrinogen-related proteins (FREPs) in Crassostrea gigas

“…Thus, five CgFREPs could be divided into three subgroups with identity cutoff points of <86% [17]. Compared with subgroup 1 (CgFREP-2 and CgFREP-4), a 138 bp insertion existed in subgroup 2 (CgFREP-1 and CgFREP-3).…”

Anopheles Fibrinogen-related Proteins Provide Expanded Pattern Recognition Capacity against Bacteria and Malaria Parasites

“…FREPs from the snail Biomphalaria glabrata are composed of two functional domains, with an N-terminal immunoglobulin (Ig) domain that may be repeated in tandem and a C-terminal FBG domain (15,16,32,33). This family has at least 14 members, of which FREP2 is an immuneresponsive protein that plays a role in host-parasite interactions (34,35). A very recent interesting observation is that the FREPs demonstrated the recognition specificities to different categories of pathogens with FREP4 bound to parasites specifically (36).…”