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 600 million 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.

The Vasopressin Receptor 2 Mutant R137L Linked to the Nephrogenic Syndrome of Inappropriate Antidiuresis (NSIAD) Signals through an Alternative Pathway that Increases AQP2 Membrane Targeting Independently of S256 Phosphorylation

“…Due to the structural similarity of the ligands and the high sequence homology of the receptors, there is some crossreactivity between them. In vitro and in vivo studies have demonstrated that oxytocin receptor can form heterodimers with V2R [43,44], although the physiological relevance of the association of oxytocin receptor with V2R remains to be determined. Interestingly, in human myometrium, oxytocin activates the Rho-ROCK pathway to phosphorylate the regulatory subunit of MLC, leading to contractions [45,46] and vasopressin can also induce uterine contractions [47].…”

Neuroprotective Properties of Peptides

“…The structure of vasopressin, a similar nonapeptide with only two amino acid differences from OXT, is extremely similar to that of OXT. Oxytocin receptor (OXTR), which together with the related V1a, V1b, and V2 vasopressin receptor subtypes form a subfamily of the large G protein-coupled receptor superfamily, is the sole receptor for OXT that is currently known [82].…”

Insect homolog of oxytocin/vasopressin associated with parenting of males but not females in a subsocial beetle

“…For example, oxytocin and vasopressin can influence aggression in both sexes, yet there is not a consistent link between either peptide, the sex it acts in, and the expression of aggression across vertebrate species (SI Table 1). However, while the sex-specificity and functions of oxytocin/vasopressin are well-understood, insects only possess a single homolog of oxytocin/vasopressin (15)(16)(17)(18), providing a unique opportunity to determine how the observed functions of the duplicates (oxytocin/vasopressin) are influenced by a single homolog (inotocin). We particularly focus on the function of inotocin in males and females, as oxytocin/vasopressin are known to show sex-specificity in their function across vertebra taxa (SI Table 1).…”

“…A single copy homologue of the oxytocin/vasopressin system - inotocin – exists in insects [16, 17]. While inotocin has been broadly associated with some social contexts in insects [17-19], it is unclear whether it has been specifically co-opted to influence parental care behaviors as most insects do not show elaborate care of their offspring with prolonged parent-offspring associations as observed in vertebrates. There are exceptions, notably burying beetles in the genus Nicrophorus where parents not only have extended associations with their offspring, they also directly provision food to their offspring by regurgitating digested carrion [20].…”

“…A single copy homologue of the oxytocin/vasopressin system -inotocin -exists in insects [16,17]. While inotocin has been broadly associated with some social contexts in insects [17][18][19], it is unclear whether it has been specifically co-opted to influence parental care behaviors as most insects do not show elaborate care of their offspring with prolonged parent-offspring associations as observed in vertebrates.…”