LeishIF4E-5 Is a Promastigote-Specific Cap-Binding Protein in <i>Leishmania</i>
<i>Leishmania</i> 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 trans...
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| Format: | Article |
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MDPI AG
2021-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/8/3979 |
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| author | Rohit Shrivastava Nitin Tupperwar Bar Schwartz Nofar Baron Michal Shapira |
| author_facet | Rohit Shrivastava Nitin Tupperwar Bar Schwartz Nofar Baron Michal Shapira |
| author_sort | Rohit Shrivastava |
| collection | DOAJ |
| description | <i>Leishmania</i> 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 <i>Leishmania</i> 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. |
| first_indexed | 2024-03-10T12:22:46Z |
| format | Article |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T12:22:46Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-01a8ccabdd144638bb177f2eb41f0dee2023-11-21T15:14:53ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-04-01228397910.3390/ijms22083979LeishIF4E-5 Is a Promastigote-Specific Cap-Binding Protein in <i>Leishmania</i>Rohit Shrivastava0Nitin Tupperwar1Bar Schwartz2Nofar Baron3Michal Shapira4Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, IsraelDepartment of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, IsraelDepartment of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, IsraelDepartment of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, IsraelDepartment of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel<i>Leishmania</i> 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 <i>Leishmania</i> 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.https://www.mdpi.com/1422-0067/22/8/3979<i>Leishmania</i>protein synthesistranslation regulationLeishIF4E-5LeishIF4G |
| spellingShingle | Rohit Shrivastava Nitin Tupperwar Bar Schwartz Nofar Baron Michal Shapira LeishIF4E-5 Is a Promastigote-Specific Cap-Binding Protein in <i>Leishmania</i> International Journal of Molecular Sciences <i>Leishmania</i> protein synthesis translation regulation LeishIF4E-5 LeishIF4G |
| title | LeishIF4E-5 Is a Promastigote-Specific Cap-Binding Protein in <i>Leishmania</i> |
| title_full | LeishIF4E-5 Is a Promastigote-Specific Cap-Binding Protein in <i>Leishmania</i> |
| title_fullStr | LeishIF4E-5 Is a Promastigote-Specific Cap-Binding Protein in <i>Leishmania</i> |
| title_full_unstemmed | LeishIF4E-5 Is a Promastigote-Specific Cap-Binding Protein in <i>Leishmania</i> |
| title_short | LeishIF4E-5 Is a Promastigote-Specific Cap-Binding Protein in <i>Leishmania</i> |
| title_sort | leishif4e 5 is a promastigote specific cap binding protein in i leishmania i |
| topic | <i>Leishmania</i> protein synthesis translation regulation LeishIF4E-5 LeishIF4G |
| url | https://www.mdpi.com/1422-0067/22/8/3979 |
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