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.

<h4>Background</h4>Protein 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. PTP1...

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Autores principales:	Debora Monteiro Moretti, Lalima Gagan Ahuja, Rodrigo Dutra Nunes, Cecília Oliveira Cudischevitch, Carlos Renato Oliveira Daumas-Filho, Priscilla Medeiros-Castro, Guilherme Ventura-Martins, Willy Jablonka, Felipe Gazos-Lopes, Raquel Senna, Marcos Henrique Ferreira Sorgine, Klaus Hartfelder, Margareth Capurro, Georgia Correa Atella, Rafael Dias Mesquita, Mário Alberto Cardoso Silva-Neto
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d92719297a4745678ca6057dfdccd377
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spelling	oai:doaj.org-article:d92719297a4745678ca6057dfdccd3772021-11-25T06:04:06ZMolecular analysis of Aedes aegypti classical protein tyrosine phosphatases uncovers an ortholog of mammalian PTP-1B implicated in the control of egg production in mosquitoes.1932-620310.1371/journal.pone.0104878https://doaj.org/article/d92719297a4745678ca6057dfdccd3772014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25137153/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Protein 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.<h4>Methodology/principal findings</h4>We 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.<h4>Conclusions/significance</h4>The 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.Debora Monteiro MorettiLalima Gagan AhujaRodrigo Dutra NunesCecília Oliveira CudischevitchCarlos Renato Oliveira Daumas-FilhoPriscilla Medeiros-CastroGuilherme Ventura-MartinsWilly JablonkaFelipe Gazos-LopesRaquel SennaMarcos Henrique Ferreira SorgineKlaus HartfelderMargareth CapurroGeorgia Correa AtellaRafael Dias MesquitaMário Alberto Cardoso Silva-NetoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 8, p e104878 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Debora Monteiro Moretti Lalima Gagan Ahuja Rodrigo Dutra Nunes Cecília Oliveira Cudischevitch Carlos Renato Oliveira Daumas-Filho Priscilla Medeiros-Castro Guilherme Ventura-Martins Willy Jablonka Felipe Gazos-Lopes Raquel Senna Marcos Henrique Ferreira Sorgine Klaus Hartfelder Margareth Capurro Georgia Correa Atella Rafael Dias Mesquita Mário Alberto Cardoso Silva-Neto 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.
description	<h4>Background</h4>Protein 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.<h4>Methodology/principal findings</h4>We 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.<h4>Conclusions/significance</h4>The 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.
format	article
author	Debora Monteiro Moretti Lalima Gagan Ahuja Rodrigo Dutra Nunes Cecília Oliveira Cudischevitch Carlos Renato Oliveira Daumas-Filho Priscilla Medeiros-Castro Guilherme Ventura-Martins Willy Jablonka Felipe Gazos-Lopes Raquel Senna Marcos Henrique Ferreira Sorgine Klaus Hartfelder Margareth Capurro Georgia Correa Atella Rafael Dias Mesquita Mário Alberto Cardoso Silva-Neto
author_facet	Debora Monteiro Moretti Lalima Gagan Ahuja Rodrigo Dutra Nunes Cecília Oliveira Cudischevitch Carlos Renato Oliveira Daumas-Filho Priscilla Medeiros-Castro Guilherme Ventura-Martins Willy Jablonka Felipe Gazos-Lopes Raquel Senna Marcos Henrique Ferreira Sorgine Klaus Hartfelder Margareth Capurro Georgia Correa Atella Rafael Dias Mesquita Mário Alberto Cardoso Silva-Neto
author_sort	Debora Monteiro Moretti
title	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.
title_short	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.
title_full	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.
title_fullStr	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.
title_full_unstemmed	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.
title_sort	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.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/d92719297a4745678ca6057dfdccd377
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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.

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