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Unique behavior of Trypanosoma cruzi mevalonate kinase: A conserved glycosomal enzyme involved in host cell invasion and signaling

Mevalonate kinase (MVK) is an essential enzyme acting in early steps of sterol isoprenoids biosynthesis, such as cholesterol in humans or ergosterol in trypanosomatids. MVK is conserved from bacteria to mammals, and localizes to glycosomes in trypanosomatids. During the course of T. cruzi MVK charac...

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Autores principales: Ferreira, Éden Ramalho, Horjales, Eduardo, Bonfim-Melo, Alexis, Cortez, Cristian, da Silva, Claudio Vieira, De Groote, Michel, Sobreira, Tiago José Paschoal, Cruz, Mário Costa, Lima, Fabio Mitsuo, Cordero, Esteban Mauricio, Yoshida, Nobuko, da Silveira, José Franco, Mortara, Renato Arruda, Bahia, Diana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4845012/
https://www.ncbi.nlm.nih.gov/pubmed/27113535
http://dx.doi.org/10.1038/srep24610
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author Ferreira, Éden Ramalho
Horjales, Eduardo
Bonfim-Melo, Alexis
Cortez, Cristian
da Silva, Claudio Vieira
De Groote, Michel
Sobreira, Tiago José Paschoal
Cruz, Mário Costa
Lima, Fabio Mitsuo
Cordero, Esteban Mauricio
Yoshida, Nobuko
da Silveira, José Franco
Mortara, Renato Arruda
Bahia, Diana
author_facet Ferreira, Éden Ramalho
Horjales, Eduardo
Bonfim-Melo, Alexis
Cortez, Cristian
da Silva, Claudio Vieira
De Groote, Michel
Sobreira, Tiago José Paschoal
Cruz, Mário Costa
Lima, Fabio Mitsuo
Cordero, Esteban Mauricio
Yoshida, Nobuko
da Silveira, José Franco
Mortara, Renato Arruda
Bahia, Diana
author_sort Ferreira, Éden Ramalho
collection PubMed
description Mevalonate kinase (MVK) is an essential enzyme acting in early steps of sterol isoprenoids biosynthesis, such as cholesterol in humans or ergosterol in trypanosomatids. MVK is conserved from bacteria to mammals, and localizes to glycosomes in trypanosomatids. During the course of T. cruzi MVK characterization, we found that, in addition to glycosomes, this enzyme may be secreted and modulate cell invasion. To evaluate the role of TcMVK in parasite-host cell interactions, TcMVK recombinant protein was produced and anti-TcMVK antibodies were raised in mice. TcMVK protein was detected in the supernatant of cultures of metacyclic trypomastigotes (MTs) and extracellular amastigotes (EAs) by Western blot analysis, confirming its secretion into extracellular medium. Recombinant TcMVK bound in a non-saturable dose-dependent manner to HeLa cells and positively modulated internalization of T. cruzi EAs but inhibited invasion by MTs. In HeLa cells, TcMVK induced phosphorylation of MAPK pathway components and proteins related to actin cytoskeleton modifications. We hypothesized that TcMVK is a bifunctional enzyme that in addition to playing a classical role in isoprenoid synthesis in glycosomes, it is secreted and may modulate host cell signaling required for T. cruzi invasion.
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spelling pubmed-48450122016-04-29 Unique behavior of Trypanosoma cruzi mevalonate kinase: A conserved glycosomal enzyme involved in host cell invasion and signaling Ferreira, Éden Ramalho Horjales, Eduardo Bonfim-Melo, Alexis Cortez, Cristian da Silva, Claudio Vieira De Groote, Michel Sobreira, Tiago José Paschoal Cruz, Mário Costa Lima, Fabio Mitsuo Cordero, Esteban Mauricio Yoshida, Nobuko da Silveira, José Franco Mortara, Renato Arruda Bahia, Diana Sci Rep Article Mevalonate kinase (MVK) is an essential enzyme acting in early steps of sterol isoprenoids biosynthesis, such as cholesterol in humans or ergosterol in trypanosomatids. MVK is conserved from bacteria to mammals, and localizes to glycosomes in trypanosomatids. During the course of T. cruzi MVK characterization, we found that, in addition to glycosomes, this enzyme may be secreted and modulate cell invasion. To evaluate the role of TcMVK in parasite-host cell interactions, TcMVK recombinant protein was produced and anti-TcMVK antibodies were raised in mice. TcMVK protein was detected in the supernatant of cultures of metacyclic trypomastigotes (MTs) and extracellular amastigotes (EAs) by Western blot analysis, confirming its secretion into extracellular medium. Recombinant TcMVK bound in a non-saturable dose-dependent manner to HeLa cells and positively modulated internalization of T. cruzi EAs but inhibited invasion by MTs. In HeLa cells, TcMVK induced phosphorylation of MAPK pathway components and proteins related to actin cytoskeleton modifications. We hypothesized that TcMVK is a bifunctional enzyme that in addition to playing a classical role in isoprenoid synthesis in glycosomes, it is secreted and may modulate host cell signaling required for T. cruzi invasion. Nature Publishing Group 2016-04-26 /pmc/articles/PMC4845012/ /pubmed/27113535 http://dx.doi.org/10.1038/srep24610 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Ferreira, Éden Ramalho
Horjales, Eduardo
Bonfim-Melo, Alexis
Cortez, Cristian
da Silva, Claudio Vieira
De Groote, Michel
Sobreira, Tiago José Paschoal
Cruz, Mário Costa
Lima, Fabio Mitsuo
Cordero, Esteban Mauricio
Yoshida, Nobuko
da Silveira, José Franco
Mortara, Renato Arruda
Bahia, Diana
Unique behavior of Trypanosoma cruzi mevalonate kinase: A conserved glycosomal enzyme involved in host cell invasion and signaling
title Unique behavior of Trypanosoma cruzi mevalonate kinase: A conserved glycosomal enzyme involved in host cell invasion and signaling
title_full Unique behavior of Trypanosoma cruzi mevalonate kinase: A conserved glycosomal enzyme involved in host cell invasion and signaling
title_fullStr Unique behavior of Trypanosoma cruzi mevalonate kinase: A conserved glycosomal enzyme involved in host cell invasion and signaling
title_full_unstemmed Unique behavior of Trypanosoma cruzi mevalonate kinase: A conserved glycosomal enzyme involved in host cell invasion and signaling
title_short Unique behavior of Trypanosoma cruzi mevalonate kinase: A conserved glycosomal enzyme involved in host cell invasion and signaling
title_sort unique behavior of trypanosoma cruzi mevalonate kinase: a conserved glycosomal enzyme involved in host cell invasion and signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4845012/
https://www.ncbi.nlm.nih.gov/pubmed/27113535
http://dx.doi.org/10.1038/srep24610
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