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Leishmania amazonensis Arginase Compartmentalization in the Glycosome Is Important for Parasite Infectivity
In Leishmania, de novo polyamine synthesis is initiated by the cleavage of L-arginine to urea and L-ornithine by the action of arginase (ARG, E.C. 3.5.3.1). Previous studies in L. major and L. mexicana showed that ARG is essential for in vitro growth in the absence of polyamines and needed for full...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3316525/ https://www.ncbi.nlm.nih.gov/pubmed/22479507 http://dx.doi.org/10.1371/journal.pone.0034022 |
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author | da Silva, Maria Fernanda Laranjeira Zampieri, Ricardo Andrade Muxel, Sandra M. Beverley, Stephen M. Floeter-Winter, Lucile M. |
author_facet | da Silva, Maria Fernanda Laranjeira Zampieri, Ricardo Andrade Muxel, Sandra M. Beverley, Stephen M. Floeter-Winter, Lucile M. |
author_sort | da Silva, Maria Fernanda Laranjeira |
collection | PubMed |
description | In Leishmania, de novo polyamine synthesis is initiated by the cleavage of L-arginine to urea and L-ornithine by the action of arginase (ARG, E.C. 3.5.3.1). Previous studies in L. major and L. mexicana showed that ARG is essential for in vitro growth in the absence of polyamines and needed for full infectivity in animal infections. The ARG protein is normally found within the parasite glycosome, and here we examined whether this localization is required for survival and infectivity. First, the localization of L. amazonensis ARG in the glycosome was confirmed in both the promastigote and amastigote stages. As in other species, arg(−) L. amazonensis required putrescine for growth and presented an attenuated infectivity. Restoration of a wild type ARG to the arg (−) mutant restored ARG expression, growth and infectivity. In contrast, restoration of a cytosol-targeted ARG lacking the glycosomal SKL targeting sequence (argΔSKL) restored growth but failed to restore infectivity. Further study showed that the ARGΔSKL protein was found in the cytosol as expected, but at very low levels. Our results indicate that the proper compartmentalization of L. amazonensis arginase in the glycosome is important for enzyme activity and optimal infectivity. Our conjecture is that parasite arginase participates in a complex equilibrium that defines the fate of L-arginine and that its proper subcellular location may be essential for this physiological orchestration. |
format | Online Article Text |
id | pubmed-3316525 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33165252012-04-04 Leishmania amazonensis Arginase Compartmentalization in the Glycosome Is Important for Parasite Infectivity da Silva, Maria Fernanda Laranjeira Zampieri, Ricardo Andrade Muxel, Sandra M. Beverley, Stephen M. Floeter-Winter, Lucile M. PLoS One Research Article In Leishmania, de novo polyamine synthesis is initiated by the cleavage of L-arginine to urea and L-ornithine by the action of arginase (ARG, E.C. 3.5.3.1). Previous studies in L. major and L. mexicana showed that ARG is essential for in vitro growth in the absence of polyamines and needed for full infectivity in animal infections. The ARG protein is normally found within the parasite glycosome, and here we examined whether this localization is required for survival and infectivity. First, the localization of L. amazonensis ARG in the glycosome was confirmed in both the promastigote and amastigote stages. As in other species, arg(−) L. amazonensis required putrescine for growth and presented an attenuated infectivity. Restoration of a wild type ARG to the arg (−) mutant restored ARG expression, growth and infectivity. In contrast, restoration of a cytosol-targeted ARG lacking the glycosomal SKL targeting sequence (argΔSKL) restored growth but failed to restore infectivity. Further study showed that the ARGΔSKL protein was found in the cytosol as expected, but at very low levels. Our results indicate that the proper compartmentalization of L. amazonensis arginase in the glycosome is important for enzyme activity and optimal infectivity. Our conjecture is that parasite arginase participates in a complex equilibrium that defines the fate of L-arginine and that its proper subcellular location may be essential for this physiological orchestration. Public Library of Science 2012-03-30 /pmc/articles/PMC3316525/ /pubmed/22479507 http://dx.doi.org/10.1371/journal.pone.0034022 Text en da Silva et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article da Silva, Maria Fernanda Laranjeira Zampieri, Ricardo Andrade Muxel, Sandra M. Beverley, Stephen M. Floeter-Winter, Lucile M. Leishmania amazonensis Arginase Compartmentalization in the Glycosome Is Important for Parasite Infectivity |
title |
Leishmania amazonensis Arginase Compartmentalization in the Glycosome Is Important for Parasite Infectivity |
title_full |
Leishmania amazonensis Arginase Compartmentalization in the Glycosome Is Important for Parasite Infectivity |
title_fullStr |
Leishmania amazonensis Arginase Compartmentalization in the Glycosome Is Important for Parasite Infectivity |
title_full_unstemmed |
Leishmania amazonensis Arginase Compartmentalization in the Glycosome Is Important for Parasite Infectivity |
title_short |
Leishmania amazonensis Arginase Compartmentalization in the Glycosome Is Important for Parasite Infectivity |
title_sort | leishmania amazonensis arginase compartmentalization in the glycosome is important for parasite infectivity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3316525/ https://www.ncbi.nlm.nih.gov/pubmed/22479507 http://dx.doi.org/10.1371/journal.pone.0034022 |
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