Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China.
Department of Entomology, Kansas State University, Manhattan, KS, United States of America.
PLoS Genet. 2020 May 4;16(5):e1008772. doi: 10.1371/journal.pgen.1008772. eCollection 2020 May.
In the postgenomics era, comparative genomics have advanced the understanding of evolutionary processes of neuropeptidergic signaling systems. The evolutionary origin of many neuropeptidergic signaling systems can be traced date back to early metazoan evolution based on the conserved sequences. Insect parathyroid hormone receptor (iPTHR) was previously described as an ortholog of vertebrate PTHR that has a well-known function in controlling bone remodeling. However, there was no sequence homologous to PTH sequence in insect genomes, leaving the iPTHR as an orphan receptor. Here, we identified the authentic ligand insect PTH (iPTH) for the iPTHR. The taxonomic distribution of iPTHR, which is lacking in Diptera and Lepidoptera, provided a lead for identifying the authentic ligand. We found that a previously described orphan ligand known as PXXXamide (where X is any amino acid) described in the cuttlefish Sepia officinalis has a similar taxonomic distribution pattern as iPTHR. Tests of this peptide, iPTH, in functional reporter assays confirmed the interaction of the ligand-receptor pair. Study of a model beetle, Tribolium castaneum, was used to investigate the function of the iPTH signaling system by RNA interference followed by RNA sequencing and phenotyping. The results suggested that the iPTH system is likely involved in the regulation of cuticle formation that culminates with a phenotype of defects in wing exoskeleton maturation at the time of adult eclosion. Moreover, RNAi of iPTHRs also led to significant reductions in egg numbers and hatching rates after parental RNAi.
在后基因组时代，比较基因组学推动了对神经肽信号系统进化过程的理解。许多神经肽信号系统的进化起源可以追溯到早期后生动物进化，这是基于保守序列得出的。昆虫甲状旁腺激素受体 (iPTHR) 以前被描述为脊椎动物 PTHR 的同源物，它在控制骨骼重塑方面具有众所周知的功能。然而，昆虫基因组中没有与 PTH 序列同源的序列，这使得 iPTHR 成为孤儿受体。在这里，我们鉴定了 iPTHR 的真正配体昆虫 PTH (iPTH)。iPTHR 在双翅目和鳞翅目昆虫中缺失，这为鉴定真正的配体提供了线索。我们发现，以前在乌贼 Sepia officinalis 中描述的一种被称为 PXXXamide（其中 X 是任何氨基酸）的孤儿配体具有与 iPTHR 相似的分类分布模式。该肽 iPTH 在功能报告基因测定中的测试证实了配体-受体对的相互作用。对模式甲虫 Tribolium castaneum 的研究通过 RNA 干扰 followed by RNA sequencing 和表型分析，研究了 iPTH 信号系统的功能。结果表明，iPTH 系统可能参与了表皮形成的调节，最终导致成虫出壳时翅膀外骨骼成熟缺陷的表型。此外，iPTHRs 的 RNAi 也导致亲代 RNAi 后卵数和孵化率显著降低。
