Evolution and Potential Function in Molluscs of Neuropeptide and Receptor Homologues of the Insect Allatostatins

Abstract

The allatostatins (ASTs), AST-A, AST-B and AST-C, have mainly been investigated in insects. They are a large group of small pleotropic alloregulatory neuropeptides that are unrelated in sequence and activate receptors of the rhodopsin G-protein coupled receptor family (GPCRs). The characteristics and functions of the homologue systems in the molluscs (Buccalin, MIP and AST-C-like), the second most diverse group of protostomes after the arthropods, and of high interest for evolutionary studies due to their less rearranged genomes remains to be explored. In the present study their evolution is deciphered in molluscs and putative functions assigned in bivalves through meta-analysis of transcriptomes and experiments. Homologues of the three arthropod AST-type peptide precursors were identified in molluscs and produce a larger number of mature peptides than in insects. The number of putative receptors were also distinct across mollusc species due to lineage and species-specific duplications. Our evolutionary analysis of the receptors identified for the first time in a mollusc, the cephalopod, GALR-like genes, which challenges the accepted paradigm that AST-AR/buccalin-Rs are the orthologues of vertebrate GALRs in protostomes. Tissue transcriptomes revealed the peptides, and their putative receptors have a widespread distribution in bivalves and in the bivalve Mytilus galloprovincialis, elements of the three peptide-receptor systems are highly abundant in the mantle an innate immune barrier tissue. Exposure of M. galloprovincialis to lipopolysaccharide or a marine pathogenic bacterium, Vibrio harveyi, provoked significant modifications in the expression of genes of the peptide precursor and receptors of the AST-C-like system in the mantle suggesting involvement in the immune response. Overall, our study reveals that homologues of the arthropod AST-systems in molluscs are potentially more complex due to the greater number of putative mature peptides and receptor genes. In bivalves they have a broad and varying tissue distribution and abundance, and the elements of the AST-C-like family may have a putative function in the immune response.

Allatostatin A Signalling: Progress and New Challenges From a Paradigmatic Pleiotropic Invertebrate Neuropeptide Family

“…However, the highest sequence similarity was found to mammalian galanin receptors [GALR, (Lenz et al, 2000a;Lenz et al, 2000b)], further members of the vertebrate SST/galanin/ opioid family of GPCRs. The close relationship of AstA-Rs with GAL-Rs is confirmed by more comprehensive sequence and structural analyses (Jékely, 2013;Mirabeau and Joly, 2013;Urlacher et al, 2016;Li et al, 2021). Collectively, these data suggest that an ancestral receptor gene duplicated twice to give rise to the ancestral AstA-R/Buccalin-R, KISS-R, and GAL-R families prior to the divergence of proto-and deuterostomia (Felix et al, 2015;Li et al, 2021).…”

“…The close relationship of AstA-Rs with GAL-Rs is confirmed by more comprehensive sequence and structural analyses (Jékely, 2013;Mirabeau and Joly, 2013;Urlacher et al, 2016;Li et al, 2021). Collectively, these data suggest that an ancestral receptor gene duplicated twice to give rise to the ancestral AstA-R/Buccalin-R, KISS-R, and GAL-R families prior to the divergence of proto-and deuterostomia (Felix et al, 2015;Li et al, 2021). This relationship of the receptors is matched by their related ligands (AstA, galanin, kisspeptin, and spexin) as outlined above.…”

“…They may indeed represent AstA orthologs as there is an astonishingly conserved gene synteny in the genomic region surrounding the nlp5/6 genes of C. elegans and AstA in insects (Felix et al, 2015). In lophotrochozoans, the mollusc buccalins (Veenstra, 2010;Cardoso et al, 2016) and AstA-like peptides ending with Lamide in Platyhelminthes (McVeigh et al, 2009) and annelids (Conzelmann et al, 2013) (Figure 1) are considered to be AstA orthologs (Li et al, 2021). Yet, clear molecular and functional evidence is lacking.…”

“…However, direct homologisation is difficult since the genomic region around vertebrate kisspeptin contains genes for two closely related peptides [galanin and spexin (Kim et al, 2014)]. (Felix et al, 2015;Li et al, 2021)]. * = GALR-like receptors have only been found in cephalopods.…”

Analysis of rhodopsin G protein-coupled receptor orthologs reveals semiochemical peptides for parasite (Schistosoma mansoni) and host (Biomphalaria glabrata) interplay

“…The elucidation of interspecies GPCR orthologs with putative ligands presented an opportunity to investigate how snail-derived biomolecules influence S. mansoni miracidia. The 5-HT is a well-established eumetazoan neurotransmitter, while and B. glabrata neuropeptides FMRFa, buccalin [recognised as AST-A homolog in molluscs 45 ] and SK have previously been identified in B. glabrata 6 , 46 , so were tested for bioactivity on miracidia. The trajectories of miracidial movement before and after addition of the FMRFa and buccalin peptides (2 µl at 100 µM) are compared in Fig.…”