Oxytocin/vasopressin-like neuropeptide signaling in insects

Abstract

The origin of the oxytocin (OT)/vasopressin (VP) signaling system is thought to date back more than 600million years. OT/VP-like peptides have been identified in numerous invertebrate phyla including molluscs, annelids, nematodes and insects. However, to date we only have a limited understanding of the biological role(s) of this GPCR-mediated signaling system in insects. This chapter presents the current knowledge of OT/VP-like neuropeptide signaling in insects by providing a brief overview of insect OT/VP-like neuropeptides, their genetic and structural commonalities, and their experimentally tested and proposed functions. Despite their widespread occurrence across insect orders these peptides (and their endogenous receptors) appear to be absent in common insect model species, such as flies and bees. We therefore explain the known functionalities of this signaling system in three different insect model systems: beetles, locusts, and ants. Additionally, we review the phylogenetic distribution of the OT/VP signaling system in arthropods as obtained from extensive genome/transcriptome mining. Finally, we discuss the unique challenges in the development of selective OT/VP ligands for human receptors and share our perspective on the possible application of insect- and other non-mammalian-derived OT/VP-like peptide ligands in pharmacology.

Keywords: Ant; Beetle; Cyclotide; GPCR; GPCR drug development; Inotocin; Insect; Locust; Oxytocin; Vasopressin.

Fig. 1

Summary of functional role of the inotocin signaling in ants, locusts and beetles. INT (inotocin), INTR (inotocin receptor), DH (diuretic hormone), MT (Malpighian tubules). Black arrows indicate experimentally tested functions and white arrows indicate suggested functions (based on weaker experimental evidence). Insect drawings were prepared by E. Gil-Mansilla.

Fig. 2

Map of inotocin peptide GPCR signaling in arthropods. A phylogenetic map based on the recently established insect phylogeny (Misof et al., 2014) is shown. The absence of the inotocin signaling system is highlighted in red. Different putative peptide sequences are shown in different colors to indicate the diversity and distribution throughout the phylogeny. The numbers in brackets next to the peptide sequences indicate the frequencies of occurrence (from a total of 121 analyzed precursor sequences that contained a mature peptide domain). Number of species where the inotocin signaling system (receptor and/or precursor) is present (INT) as well as the total number of sampled species(T) has been indicated next to the tree branches. The inotocin signaling system is confined to specific groups of arthropods. For clarity of this phylogenetic illustration, the upper three groups of Arthropoda (Chelicerata, Myriapoda and Crustaceans; underlined) represent subphyla. All other groups denote orders of the subphylum Hexapoda; the class of Insecta comprises the orders Archaeognatha to Diptera. Reproduced from Liutkevičiūte, Z., Koehbach, J., Eder, T., Gil-Mansilla, E., & Gruber, C. W. (2016). Global map of oxytocin/vasopressin-like neuropeptide signalling in insects. Scientific Reports, 6,39177. 10.1038/srep39177 with permission under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http:/creativecommons.org/licenses/by/4.0/.