Abstract
Venus kinase receptors (VKRs) are invertebrate receptor tyrosine kinases (TKs) first discovered in the human parasite Schistosoma. They contain an extracellular Venus FlyTrap module similar to the ligand-binding domain of G protein-coupled receptors of class C and an intracellular TK domain similar to that of insulin receptors. VKRs are present from cnidarians to echinoderms. They were shown to be activated by amino-acids, to induce insulin-like intracellular pathways, and to be highly expressed in larvae and in gonads of helminths and insects. The function of VKR in gametogenesis was demonstrated in schistosomes by VKR silencing and recent studies in Aedes aegypti have confirmed the importance of VKR in mosquito egg formation. AaeVKR was shown to bind to ovary ecdysteroidogenic hormone and to activate the production of ecdysteroids by the ovary, independently of signaling mediated by insulin-like peptides. These new data confirm and specify the function of VKRs in the reproduction of helminths and insects and they open interesting perspectives for elucidating the role of VKRs in other models. VKR targeting would also provide opportunities for the control of parasites and various vector-borne infectious diseases.
Highlights
Specialty section: This article was submitted to Molecular and Structural Endocrinology, a section of the journal Frontiers in Endocrinology
Venus kinase receptors (VKRs) were subsequently discovered in other species and shown to belong to a new family of receptor tyrosine kinases (RTKs), present only in invertebrates from at least five phyla of the Bilateria branch (Platyhelminthes, Arthropoda, Annelida, Mollusca, Echinodermata) as well as to the Cnidaria phylum [2, 3]
Such RTKs are found in a large majority of insects including several Drosophila species but exceptionally vkr genes are absent from the genome of Drosophila melanogaster as well as from the genomes of other species in the melanogaster subgroup
Summary
Insulin and Insulin-like growth factor signaling (IIS) forms complex networks with other signaling pathways, especially with the amino-acid-sensing TOR (target of rapamycin)/S6K (p70 S6 kinase) pathway, to regulate nutrition, growth, development, longevity, as well as reproduction [8, 9]. The in vitro treatment of schistosomes with commercial IR kinase inhibitors, like tyrphostin AG1024 and HNMP-A3, led to dramatic effects on fertility and viability of larval and adult parasites [23] These data support a potential importance of IIS in reproduction of helminths, similar to its role in insects. AaeVKR knockdown has no effect on ovary ecdysteroid production mediated by ILP3, and these data confirm a unique and specific role of VKR in the activation of egg formation in the mosquito [7]. Even though it has not yet been demonstrated that SmE78 could be involved in the transduction of an ecdysone signal required for the regulation of egg formation, it is tempting to hypothesize a putative function of schistosome VKR in the production of ecdysteroids similar to that shown in mosquitoes
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