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LeishIF4E-5 Is a Promastigote-Specific Cap-Binding Protein in Leishmania
Leishmania parasites cycle between sand fly vectors and mammalian hosts, transforming from extracellular promastigotes that reside in the vectors’ alimentary canal to obligatory intracellular non-motile amastigotes that are harbored by macrophages of the mammalian hosts. The transition between vecto...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069130/ https://www.ncbi.nlm.nih.gov/pubmed/33921489 http://dx.doi.org/10.3390/ijms22083979 |
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author | Shrivastava, Rohit Tupperwar, Nitin Schwartz, Bar Baron, Nofar Shapira, Michal |
author_facet | Shrivastava, Rohit Tupperwar, Nitin Schwartz, Bar Baron, Nofar Shapira, Michal |
author_sort | Shrivastava, Rohit |
collection | PubMed |
description | Leishmania parasites cycle between sand fly vectors and mammalian hosts, transforming from extracellular promastigotes that reside in the vectors’ alimentary canal to obligatory intracellular non-motile amastigotes that are harbored by macrophages of the mammalian hosts. The transition between vector and host exposes them to a broad range of environmental conditions that induces a developmental program of gene expression, with translation regulation playing a key role. The Leishmania genome encodes six paralogs of the cap-binding protein eIF4E. All six isoforms show a relatively low degree of conservation with eIF4Es of other eukaryotes, as well as among themselves. This variability could suggest that they have been assigned discrete roles that could contribute to their survival under the changing environmental conditions. Here, we describe LeishIF4E-5, a LeishIF4E paralog. Despite the low sequence conservation observed between LeishIF4E-5 and other LeishIF4Es, the three aromatic residues in its cap-binding pocket are conserved, in accordance with its cap-binding activity. However, the cap-binding activity of LeishIF4E-5 is restricted to the promastigote life form and not observed in amastigotes. The overexpression of LeishIF4E-5 shows a decline in cell proliferation and an overall reduction in global translation. Immuno-cytochemical analysis shows that LeishIF4E-5 is localized in the cytoplasm, with a non-uniform distribution. Mass spectrometry analysis of proteins that co-purify with LeishIF4E-5 highlighted proteins involved in RNA metabolism, along with two LeishIF4G paralogs, LeishIF4G-1 and LeishIF4G-2. These vary in their conserved eIF4E binding motif, possibly suggesting that they can form different complexes. |
format | Online Article Text |
id | pubmed-8069130 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-80691302021-04-26 LeishIF4E-5 Is a Promastigote-Specific Cap-Binding Protein in Leishmania Shrivastava, Rohit Tupperwar, Nitin Schwartz, Bar Baron, Nofar Shapira, Michal Int J Mol Sci Article Leishmania parasites cycle between sand fly vectors and mammalian hosts, transforming from extracellular promastigotes that reside in the vectors’ alimentary canal to obligatory intracellular non-motile amastigotes that are harbored by macrophages of the mammalian hosts. The transition between vector and host exposes them to a broad range of environmental conditions that induces a developmental program of gene expression, with translation regulation playing a key role. The Leishmania genome encodes six paralogs of the cap-binding protein eIF4E. All six isoforms show a relatively low degree of conservation with eIF4Es of other eukaryotes, as well as among themselves. This variability could suggest that they have been assigned discrete roles that could contribute to their survival under the changing environmental conditions. Here, we describe LeishIF4E-5, a LeishIF4E paralog. Despite the low sequence conservation observed between LeishIF4E-5 and other LeishIF4Es, the three aromatic residues in its cap-binding pocket are conserved, in accordance with its cap-binding activity. However, the cap-binding activity of LeishIF4E-5 is restricted to the promastigote life form and not observed in amastigotes. The overexpression of LeishIF4E-5 shows a decline in cell proliferation and an overall reduction in global translation. Immuno-cytochemical analysis shows that LeishIF4E-5 is localized in the cytoplasm, with a non-uniform distribution. Mass spectrometry analysis of proteins that co-purify with LeishIF4E-5 highlighted proteins involved in RNA metabolism, along with two LeishIF4G paralogs, LeishIF4G-1 and LeishIF4G-2. These vary in their conserved eIF4E binding motif, possibly suggesting that they can form different complexes. MDPI 2021-04-12 /pmc/articles/PMC8069130/ /pubmed/33921489 http://dx.doi.org/10.3390/ijms22083979 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Shrivastava, Rohit Tupperwar, Nitin Schwartz, Bar Baron, Nofar Shapira, Michal LeishIF4E-5 Is a Promastigote-Specific Cap-Binding Protein in Leishmania |
title | LeishIF4E-5 Is a Promastigote-Specific Cap-Binding Protein in Leishmania |
title_full | LeishIF4E-5 Is a Promastigote-Specific Cap-Binding Protein in Leishmania |
title_fullStr | LeishIF4E-5 Is a Promastigote-Specific Cap-Binding Protein in Leishmania |
title_full_unstemmed | LeishIF4E-5 Is a Promastigote-Specific Cap-Binding Protein in Leishmania |
title_short | LeishIF4E-5 Is a Promastigote-Specific Cap-Binding Protein in Leishmania |
title_sort | leishif4e-5 is a promastigote-specific cap-binding protein in leishmania |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069130/ https://www.ncbi.nlm.nih.gov/pubmed/33921489 http://dx.doi.org/10.3390/ijms22083979 |
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