Individual sequence variability and functional activities of fibrinogen-related proteins (FREPs) in the Mediterranean mussel (Mytilus galloprovincialis) suggest ancient and complex immune recognition models in invertebrates

Abstract

In this paper, we describe sequences of fibrinogen-related proteins (FREPs) in the Mediterranean mussel Mytilus galloprovincialis (MuFREPs) with the fibrinogen domain probably involved in the antigen recognition, but without the additional collagen-like domain of ficolins, molecules responsible for complement activation by the lectin pathway. Although they do not seem to be true or primive ficolins since the phylogenetic analysis are not conclusive enough, their expression is increased after bacterial infection or PAMPs treatment and they present opsonic activities similar to mammalian ficolins. The most remarkable aspect of these sequences was the existence of a very diverse set of FREP sequences among and within individuals (different mussels do not share any identical sequence) which parallels the extraordinary complexity of the immune system, suggesting the existence of a primitive system with a potential capacity to recognize and eliminate different kind of pathogens.

Toll signal transduction pathway in bivalves: Complete cds of intermediate elements and related gene transcription levels in hemocytes of immune stimulated Mytilus galloprovincialis

“…Details related to the experimental challenges (e.g. live versus heat-inactivated microbes, shell notching versus shell slitting), differences in sampling time and also extended individual variability of AMP gene transcription levels (Cantet et al, , 2009aRomero et al, 2011) generated contrasted results and do not allow to draw a common scheme. Finally, gene transcription depends on half-time and degradation rate of proteins after challenge, as demonstrated in Drosophila (Nicolas et al, 1998).…”

Characteristic and functional analysis of a ficolin-like protein from the oyster Crassostrea hongkongensis

“…Only a few reports have described FREPs in mollusks, although these invertebrates are the second most diverse group of animals (next to arthropods) with approximately 93,000 extant species [19]. Mediterranean mussels showed increased MmFREPs expression after bacterial infection or pathogen-associated molecular patterns (PAMP) treatment, and these proteins exhibited opsonic activities similar to mammalian ficolins [14]. In other shellfish mollusks, such as the scallop Argopecten irradians, AiFREP was identified as a pattern recognition receptor in the immune response [20].…”

“…Thus, FREPs are important members of the host innate immune response against pathogens [9,17,18]. Many FREPs have been identified in different animal species, including vertebrates, urochordates and invertebrates [7,14,16]. Only a few reports have described FREPs in mollusks, although these invertebrates are the second most diverse group of animals (next to arthropods) with approximately 93,000 extant species [19].…”

“…FREPs are a group of glycoproteins containing an FGB domain at the C-terminus but different domains at the N-terminus [14]. The members of this protein family include fibrinogen, MFAP4, angiopoietin, tachylectins, tenascins, fibroleukin, FIBCD1 and ficolins [15,16].…”

MIF from mussel: Coding sequence, phylogeny, polymorphism, 3D model and regulation of expression

“…Among the remaining amino acid sequences, 9 were encountered only once or twice. Several other proteins were previously reported as highly polymorphic in mussels: antimicrobial peptides defensin, mytilin (Parisi et al, 2009) and particularly myticin (Costa et al, 2009;Pallavicini et al, 2008), C1q-like (Gerdol et al, 2011;Gestal et al, 2010), FREPs (Romero et al, 2011) and antifungal mytimycin (Sonthi et al, 2011). Although not understood, no doubt that the existence of numerous variants probably corresponds to as yet undefined functional mechanism(s).…”