The ligand of parathyroid hormone like receptors in invertebrates has been identified for the first time by Professor Bin Li's research group in the College of Life Sciences in Nanjing Normal University. This study was published in PLoS Genetics under the title of "A new neuropeptide insect parathyroid hormone iPTH in the red flour beetle Tribolium castaneum". Professor Li Bin of Nanjing Normal University, Professor Yoonseong Park of Kansas State University in the United States and Professor Jan A. Veenstra of University of Bordeaux in France are the co-corresponding authors of the paper. Dr. Jia Xie and Dr. Ming Sang of Nanjing Normal University are the co-first authors. PLoS Genetics is a classic journal in the field of biology, which has a five-year impact factor of 6.283.
Vertebrate parathyroid hormone (PTH) and its receptors have been extensively studied with respect to their function in bone remodeling and calcium metabolism. Insect parathyroid hormone receptors (iPTHRs) have been firstly described as counterparts of vertebrate PTHRs by Professor Bin Li's research group in 2013（Paper title: Comparative genomic analysis and evolution of family-B G protein-coupled receptors from six model insect species）, and subsequently were confirmed by another group in 2014. However, iPTHRs are still orphan receptors for which the authentic ligands and biological functions remain unknown. In addition, insects do not have kidneys and skeletons, thus the biological function of this signal system in insects still needs further exploration.
Here, Professor Bin Li’s group has uncovered the authentic ligand for the iPTHRs. The strategy for deorphanization of this ancestral GPCR utilized a genomic survey of numerous species in insects and further basal lineages. The similar patterns of taxonomic distributions of iPTHRs and of neuropeptide-like sequences were searched and they found that the taxonomic distribution of the neuropeptide previously described as PXXXamide (where X is any amino acid) in the cuttlefish Sepia officinalis (Mollusca), is in a mirror image of the distribution pattern of iPTHRs. Specifically, the loss of iPTHRs in Diptera and Lepidoptera coincided with the absence of this specific neuropeptide in the same taxa. They demonstrated that this previously uncharacterized neuropeptide is an active ligand on these receptors and named the peptide insect PTH (iPTH). The immunohistochemical results exhibited that both of iPTH and iPTHR1 have high expression in late pupal stage, central nervous system and gut tissue. Additionally, the phenotypes from RNA interferences (RNAi) and the RNA-seq data suggest that the iPTH system is involved in the maturation of the exoskeletal cuticle in the wings at the time of adult eclosion.
The significance of this paper is the insect parathyroid hormone was firstly identified by analyzing its interactions with iPTHRs, and their functions were also investigated. The results have filled the blank of the study on the relationship between the iPTHRs and its ligands and their mechanism in invertebrates. It can not only help to elucidate the function and regulatory mechanism of this signal system in the process of insect growth and development, but also promote the understanding of its evolution in metazoan. Finally, it may be also useful for the exploration of new drug targets.