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.
Highlights
Tyrosine phosphorylation is part of a complex cell repertoire that first appeared nearly 600-million years ago and is largely responsible for the emergence of the first multicellular animals [1].Protein tyrosine phosphatases (PTPs) are enzymes that catalyze tyrosine dephosphorylation and regulate central steps of cell biology
The search for Protein Tyrosine Phosphatases (PTPs) sequences in the Aedes aegypti genome has led to the discovery of 8 PTP genes coding for 10 proteins belonging to Class I soluble PTPs: AAEL001046, AAEL001919
Among the genes that code for classical PTPs in Aedes, two, AAEEL001919 and
Summary
Tyrosine phosphorylation is part of a complex cell repertoire that first appeared nearly 600-million years ago and is largely responsible for the emergence of the first multicellular animals [1]. Aedes aegypti is the vector of Dengue and yellow fever Once it feeds on blood, a complex series of signaling events lead to yolk synthesis and egg formation. In the study reported we conducted a bioinformatics analysis of the A. aegypti genome to identify the mosquito ortholog of PTP1B and determine its involvement in egg formation [13]. The inhibition of these regulators or the blocking of proteins under their transcriptional control can potentially provide new targets for suppression of egg formation and pathogen transmission by mosquitoes [14]. AAEL001919 may present a potential target for the control of tyrosine phosphorylation in mosquitoes and may be used to decrease mosquito reproduction
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