Repertoires of G protein-coupled receptors for Ciona-specific neuropeptides
Repertoires of G protein-coupled receptors for Ciona-specific neuropeptides
复制标题
DOI：
10.1073/pnas.1816640116
复制
发表时间：
2019-04-16
影响因子：
11.1
通讯作者：
Satake，Honoo
中科院分区：
文献类型：
--
作者：
Shiraishi，Akira;Okuda，Toshimi;Satake，Honoo
神经肽在神经、神经内分泌和内分泌系统的各种生物学事件中起着关键作用，与动物的生理功能和独特的行为特征密切相关。阐明神经肽和受体之间的功能相互作用是验证其生物学作用和进化过程的关键步骤。然而，大多数新型肽的受体仍有待鉴定。在这里，我们展示了多个G蛋白偶联受体（GPCR）的脊椎动物的姐妹群，玻璃海鞘A型，物种特异性神经肽的识别，结合机器学习和实验验证。我们开发了一个原始的肽结合支持向量机，并用它来预测22神经肽GPCR对。值得注意的是，预测对的信号传导测定鉴定了1个同源的和11个Ciona特异性神经肽-GPCR对，命中率为41%：C1-GALP、C1-NTLP-2、C1-LF-1、C1-LF-2、C1-LF-5、C1-LF-6、C1-LF-7、C1-LF-8、C1-YFV-1和C1-YFV-3的相应GPCR。有趣的是，分子系统发育树分析显示，这些受体（不包括Ci-GALP受体）在进化上与任何其他已知的肽GPCR无关，证实了这些GPCR构成了前所未有的神经肽受体簇。总之，这些结果证实了神经肽GPCR对在原脊索动物和进化谱系的神经肽GPCR，并铺平了道路，调查内源性的作用，新的神经肽在脊椎动物的近亲和整个脊索动物的神经肽能系统的进化过程。此外，本研究还表明了机器学习辅助策略在各种生物体中识别新型肽受体对的多功能性。
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 intestinalisType 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 11Ciona-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.