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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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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. |
format | Online Article Text |
id | pubmed-4845012 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
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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