Somatostatin-type and allatostatin-C–type neuropeptides are paralogous and have opposing myoregulatory roles in an echinoderm

Abstract

Somatostatin (SS) and allatostatin-C (ASTC) are inhibitory neuropeptides in chordates and protostomes, respectively, which hitherto were identified as orthologs. However, echinoderms have two SS/ASTC-type neuropeptides (SS1 and SS2), and here, our analysis of sequence data indicates that SS1 is an ortholog of ASTC and SS2 is an ortholog of SS. The occurrence of both SS-type and ASTC-type neuropeptides in echinoderms provides a unique context to compare their physiological roles. Investigation of the expression and actions of the ASTC-type neuropeptide ArSS1 in the starfish Asterias rubens revealed that it causes muscle contraction (myoexcitation), contrasting with myoinhibitory effects of the SS-type neuropeptide ArSS2. Our findings suggest that SS-type and ASTC-type neuropeptides are paralogous and originated by gene duplication in a common ancestor of the Bilateria, with only one type being retained in chordates (SS) and protostomes (ASTC) but with both types being retained in echinoderms. Loss of ASTC-type and SS-type neuropeptides in chordates and protostomes, respectively, may have been due to their functional redundancy as inhibitory regulators of physiological processes. Conversely, the retention of both neuropeptide types in echinoderms may be a consequence of the evolution of a myoexcitatory role for ASTC-type neuropeptides mediated by as yet unknown signaling mechanisms.

System-wide mapping of neuropeptide-GPCR interactions inC. elegans

“…This group of 12 C. elegans GPCRs (Data S9) includes NPR-17 that was previously shown to interact with the opioid-like peptide NLP-24 48 . We found two other receptors in this family, NPR-24 and NPR-32, to interact with previously recognized orthologs of the SST/AstC neuropeptide family, NLP-62 and NLP-64 (Figure S2), supporting the conservation of SST/AstC-like receptors in C. elegans 42, 104 .…”

“…Indeed, many of the receptors we deorphanized belong to expanded GPCR families for which specific ligands could not have been predicted based on available data, as the corresponding neuropeptide families ( e.g. RFamide, sNPF, and somatostatin-like peptides) have diversified in nematodes as well 42, 104 . The neuropeptide-receptor pairs that we discovered can facilitate future predictions of peptide-GPCR couples in C. elegans as well as other species, such as parasitic nematodes, which may speed up the discovery of drug targets.…”

“…Indeed, many of the receptors we deorphanized belong to expanded GPCR families for which specific ligands could not have been predicted based on available data, as the corresponding neuropeptide families (e.g. RFamide, sNPF, and somatostatin-like peptides) have diversified in nematodes as well 42,104 .…”

Receptor deorphanization in an echinoderm reveals kisspeptin evolution and relationship with SALMFamide neuropeptides

“…Thirdly, we have performed a mass spectrometric analysis of radial nerve cord extracts from this species, which has enabled the determination of the mature structure of neuropeptides, as reported previously for many other neuropeptide types [36-40, 42, 43, 45-47] and as reported here for kisspeptin-related neuropeptides. Lastly, we have established A. rubens as an experimental model for functional characterization of neuropeptide signaling systems [36,38,40,41,43,[45][46][47][48][49], which provides a strong basis for future investigations of the physiological roles of kisspeptin-type neuropeptides in this species.…”

Nervous System Development and Neuropeptides Characterization in Embryo and Larva: Insights from a Non-Chordate Deuterostome, the Sea Cucumber Apostichopus japonicus

“…Neuropeptides are considered to be the oldest neuronal signaling molecules in metazoans, which makes them optimal tracers for neuroendocrine activity [ 26 , 27 , 28 ]. Studies of marine invertebrate neuropeptide systems have been revealed in Mollusca, annelids, marine arthropods (crustaceans) and echinoderms [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. In echinoderms, the recent development of RNA high-throughout sequencing technology has allowed strong advances in the identification and characterization of neuropeptides in adults [ 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ].…”