RRC ID 73386
Author Shiraishi A, Okuda T, Miyasaka N, Osugi T, Okuno Y, Inoue J, Satake H.
Title Repertoires of G protein-coupled receptors for Ciona-specific neuropeptides.
Journal Proc Natl Acad Sci U S A
Abstract Neuropeptides play pivotal roles in various biological events in the nervous, neuroendocrine, and endocrine systems, and are correlated with both physiological functions and unique behavioral traits of animals. Elucidation of functional interaction between neuropeptides and receptors is a crucial step for the verification of their biological roles and evolutionary processes. However, most receptors for novel peptides remain to be identified. Here, we show the identification of multiple G protein-coupled receptors (GPCRs) for species-specific neuropeptides of the vertebrate sister group, Ciona intestinalis Type A, by combining machine learning and experimental validation. We developed an original peptide descriptor-incorporated support vector machine and used it to predict 22 neuropeptide-GPCR pairs. Of note, signaling assays of the predicted pairs identified 1 homologous and 11 Ciona-specific neuropeptide-GPCR pairs for a 41% hit rate: the respective GPCRs for Ci-GALP, Ci-NTLP-2, Ci-LF-1, Ci-LF-2, Ci-LF-5, Ci-LF-6, Ci-LF-7, Ci-LF-8, Ci-YFV-1, and Ci-YFV-3. Interestingly, molecular phylogenetic tree analysis revealed that these receptors, excluding the Ci-GALP receptor, were evolutionarily unrelated to any other known peptide GPCRs, confirming that these GPCRs constitute unprecedented neuropeptide receptor clusters. Altogether, these results verified the neuropeptide-GPCR pairs in the protochordate and evolutionary lineages of neuropeptide GPCRs, and pave the way for investigating the endogenous roles of novel neuropeptides in the closest relatives of vertebrates and the evolutionary processes of neuropeptidergic systems throughout chordates. In addition, the present study also indicates the versatility of the machine-learning-assisted strategy for the identification of novel peptide-receptor pairs in various organisms.
Volume 116(16)
Pages 7847-7856
Published 2019-4-16
DOI 10.1073/pnas.1816640116
PII 1816640116
PMID 30936317
PMC PMC6475428
MeSH Animals Ciona intestinalis* / chemistry Ciona intestinalis* / genetics Ciona intestinalis* / metabolism Computational Biology Neuropeptides* / chemistry Neuropeptides* / genetics Neuropeptides* / metabolism Receptors, G-Protein-Coupled* / chemistry Receptors, G-Protein-Coupled* / genetics Receptors, G-Protein-Coupled* / metabolism Receptors, Neuropeptide* / chemistry Receptors, Neuropeptide* / genetics Receptors, Neuropeptide* / metabolism Support Vector Machine
IF 9.412
C.intestinalis / (O.japonicus) Wild C. int