A new neuropeptide insect parathyroid hormone iPTH in the red flour beetle Tribolium castaneum

Abstract

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.

Nemertean, Brachiopod, and Phoronid Neuropeptidomics Reveals Ancestral Spiralian Signaling Systems

“…To further assess the potential homology of CCWamide and ALP peptides, we carried out a gene structure analysis, which is a powerful tool in homology assessments for neuropeptide precursors ( Mair et al 2000 ; Yañez Guerra et al 2020 ; Zhang et al 2020 ). The gene structure comparison of CCWamides from the mollusk Crassostrea virginica , the phoronid P. australis and the nemertean Notospermus geniculatus with the ALP of the flour beetle Tribolium castaneum and the three agatoxin paralogs of the arachnid Centruroides sculpturatus reveals a conserved intron–exon structure of the precursors ( fig.…”

“…GPCRs are several hundred amino acids long and their degree of conservation make phylogenetic analyses feasible when reconstructing the evolution of peptidergic systems ( Jékely 2013 ; Mirabeau and Joly 2013 ). Another useful approach is to compare the exon–intron structure of pNPs ( Mair et al 2000 ; Yañez Guerra et al 2020 ; Zhang et al 2020 ). In several cases, the overall organization of orthologous pNP genes can be conserved (e.g., a region coding for the signal peptide followed by a single peptide and a C-terminal Cys-containing domain) ( Semmens et al 2015 ; Liutkeviciute et al 2016 ).…”

“…In several cases, the overall organization of orthologous pNP genes can be conserved (e.g., a region coding for the signal peptide followed by a single peptide and a C-terminal Cys-containing domain) ( Semmens et al 2015 ; Liutkeviciute et al 2016 ). Furthermore, an increased sampling across taxa has often helped to clarify relationships, revealing hidden orthologs or lineage-specific losses, gains, and divergences ( Jékely 2013 ; Mirabeau and Joly 2013 ; Semmens et al 2016 ; Martín-Durán et al 2017 ; Thiel et al 2018 ; Yañez Guerra et al 2020 ). Some lineages can retain signaling systems that had been lost in related species.…”

Hormonal axes in Drosophila: regulation of hormone release and multiplicity of actions

“…In Drosophila melanogaster , the peptidome is somewhat reduced compared to species in basal insect orders but also compared to some other Drosophila species (Liessem et al 2018 ; Nässel and Zandawala 2019 ; Veenstra 2010 ; Veenstra and Khammassi 2017 ). For instance, vasopressin-like peptide (inotocin), AKH/corazonin-related peptide (ACP), allatotropin, calcitonin, elevenin, neuroparsin, parathyroid hormone–like peptide and TRH genes have been lost (Nässel and Zandawala 2019 ; Veenstra and Šimo 2020 ; Xie et al 2020 ). This may suggest that in Drosophila , other peptides have taken over the roles of the missing ones (see examples of JH regulation below).…”

Transcriptome Profiling of the Pacific Oyster Crassostrea gigas Visceral Ganglia over a Reproduction Cycle Identifies Novel Regulatory Peptides

“…The biological function of QSamide and PXXXamide is still unknown. A PXXXamide was recently found to activate an ortholog of a vertebrate parathyroid hormone receptor (PTHR) in the red flour beetle ( Tribolium castaneum ) [ 97 ]. Considering that a PTHR ortholog is female-gonad-specific in C. gigas [ 98 ], the oyster PXXXamide/PTHR signaling system can be expected to regulate some key steps of female gametogenesis, with possible major outcomes in terms of female fecundity.…”