Dual role of the Anopheles coluzzii Venus Kinase Receptor in both larval growth and immunity

Nadège Gouignard,Floriane Cherrier,Corinne Genève,Christian Mitri,Natalia Marta Zmarlak,Adrien Pain,Kenneth D Vernick,Katia Cailliau,Colette Dissous,Emma Brito-Fravallo

doi:10.1038/s41598-019-40407-x

Abstract

Vector-borne diseases and especially malaria are responsible for more than half million deaths annually. The increase of insecticide resistance in wild populations of Anopheles malaria vectors emphasises the need for novel vector control strategies as well as for identifying novel vector targets. Venus kinase receptors (VKRs) constitute a Receptor Tyrosine Kinase (RTK) family only found in invertebrates. In this study we functionally characterized Anopheles VKR in the Gambiae complex member, Anophelescoluzzii. Results showed that Anopheles VKR can be activated by L-amino acids, with L-arginine as the most potent agonist. VKR was not required for the fecundity of A. coluzzii, in contrast to reports from other insects, but VKR function is required in both Anopheles males and females for development of larval progeny. Anopheles VKR function is also required for protection against infection by Plasmodium parasites, thus identifying a novel linkage between reproduction and immunity in Anopheles. The insect specificity of VKRs as well as the essential function for reproduction and immunity suggest that Anopheles VKR could be a potentially druggable target for novel vector control strategies.

Highlights

Vector-borne diseases account for more than 17% of all infectious diseases, causing more than 700,000 deaths annually[1]
We cloned the Venus Kinase Receptors (VKRs) gene from an A. coluzzi laboratory strain and expressed the protein in stage VI Xenopus oocytes. These cells are blocked in the first period of meiosis but activation of Receptor Tyrosine Kinase (RTK) can induce further kinase signalling cascades and Akt and MAPK phosphorylation can result in meiosis resumption and Germinal Vesical BreakDown (GVBD)[17]
We report the functional characterization of a member of the VKR family in the mosquito vector A. coluzzii

Summary

Introduction

Vector-borne diseases account for more than 17% of all infectious diseases, causing more than 700,000 deaths annually[1]. Transcripts of vkr were found to be abundant in larval forms and in female ovaries of the platyhelminth S. mansoni[13] and of several insects like Tribolium castaneum, Apis mellifera, Anopheles gambiae[9] They were found in the ovaries of Aedes aegypti[14] and more recently in the gonads of the desert locust, Schistocerca gregaria[15]. We cloned the VKR gene from an A. coluzzi laboratory strain and expressed the protein in stage VI Xenopus oocytes These cells are blocked in the first period of meiosis (metaphase 1) but activation of RTK can induce further kinase signalling cascades and Akt and MAPK phosphorylation can result in meiosis resumption and Germinal Vesical BreakDown (GVBD)[17]. Functional studies using RNAi-mediated gene silencing revealed a dual role for the A. coluzzii VKR in both the reproduction of this insect, as well as immunity against infection with malaria parasites

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Conclusion