2019年4月
Repertoires of G protein-coupled receptors for Ciona-specific neuropeptides
Proceedings of the National Academy of Sciences of the United States of America
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- 巻
- 116
- 号
- 16
- 開始ページ
- 7847
- 終了ページ
- 7856
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1073/pnas.1816640116
- 出版者・発行元
- NATL ACAD SCIENCES
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.
- リンク情報
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- DOI
- https://doi.org/10.1073/pnas.1816640116
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/30936317
- PubMed Central
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6475428
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000464767500042&DestApp=WOS_CPL
- Scopus
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85064339101&origin=inward 本文へのリンクあり
- Scopus Citedby
- https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85064339101&origin=inward
- ID情報
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- DOI : 10.1073/pnas.1816640116
- ISSN : 0027-8424
- eISSN : 1091-6490
- PubMed ID : 30936317
- PubMed Central 記事ID : PMC6475428
- SCOPUS ID : 85064339101
- Web of Science ID : WOS:000464767500042