Molecular Analysis of Aedes aegypti Classical Protein Tyrosine Phosphatases Uncovers an Ortholog of Mammalian PTP-1B Implicated in the Control of Egg Production in Mosquitoes

Abstract

BackgroundProtein Tyrosine Phosphatases (PTPs) are enzymes that catalyze phosphotyrosine dephosphorylation and modulate cell differentiation, growth and metabolism. In mammals, PTPs play a key role in the modulation of canonical pathways involved in metabolism and immunity. PTP1B is the prototype member of classical PTPs and a major target for treating human diseases, such as cancer, obesity and diabetes. These signaling enzymes are, hence, targets of a wide array of inhibitors. Anautogenous mosquitoes rely on blood meals to lay eggs and are vectors of the most prevalent human diseases. Identifying the mosquito ortholog of PTP1B and determining its involvement in egg production is, therefore, important in the search for a novel and crucial target for vector control.Methodology/Principal FindingsWe conducted an analysis to identify the ortholog of mammalian PTP1B in the Aedes aegypti genome. We identified eight genes coding for classical PTPs. In silico structural and functional analyses of proteins coded by such genes revealed that four of these code for catalytically active enzymes. Among the four genes coding for active PTPs, AAEL001919 exhibits the greatest degree of homology with the mammalian PTP1B. Next, we evaluated the role of this enzyme in egg formation. Blood feeding largely affects AAEL001919 expression, especially in the fat body and ovaries. These tissues are critically involved in the synthesis and storage of vitellogenin, the major yolk protein. Including the classical PTP inhibitor sodium orthovanadate or the PTP substrate DiFMUP in the blood meal decreased vitellogenin synthesis and egg production. Similarly, silencing AAEL001919 using RNA interference (RNAi) assays resulted in 30% suppression of egg production.Conclusions/SignificanceThe data reported herein implicate, for the first time, a gene that codes for a classical PTP in mosquito egg formation. These findings raise the possibility that this class of enzymes may be used as novel targets to block egg formation in mosquitoes.

Roles of the PTP61F Gene in Regulating Energy Metabolism of Tribolium castaneum (Coleoptera: Tenebrionidae)

“…However, there are few studies of PTP1B in insects. In A. aegypti, it has been reported to occur in all tissues, and it is highly expressed in the ovaries (Moretti et al, 2014). In this study, we found that TcPTP61F is expressed in a variety of T. castaneum tissues.…”

Polyphenol-Rich Diets Exacerbate AMPK-Mediated Autophagy, Decreasing Proliferation of Mosquito Midgut Microbiota, and Extending Vector Lifespan

“…The role of the AMPK gene in the control of A . aegypti midgut microbiota was assessed using RNA interference-mediated gene silencing, as described previously [ 26 ]. In brief, dsRNAs were constructed using in-vitro transcription with the HiScribe T7 In Vitro Transcription Kit (New England Biolabs).…”

RNA Interference for Mosquito and Mosquito-Borne Disease Control

“…Preventing oogenesis, diminishing the number of female adults through sexual dependency genes, and producing sterile males are viable approaches to population control. Numerous genes limit egg batch size and nutrient uptake through disruption of nutrient regulation and developmental processes in the oocyte [18,27,56,83,100,105,106,107,108,109]. For instance, targeting genes such as kir in An.…”