Translational Control through eIF2alpha Phosphorylation during the Leishmania Differentiation Process
| العنوان: | Translational Control through eIF2alpha Phosphorylation during the Leishmania Differentiation Process |
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| المؤلفون: | Nathalie Boilard, Marie-Noelle Chou, Conan Chow, Barbara Papadopoulou, Serge Cloutier, Maxime Laverdière |
| المصدر: | PLoS ONE PLoS ONE, Vol 7, Iss 5, p e35085 (2012) |
| بيانات النشر: | Public Library of Science, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Eukaryotic Initiation Factor-2, lcsh:Medicine, Protozoology, Microbiology, 03 medical and health sciences, 0302 clinical medicine, Eukaryotic translation, Stress, Physiological, Polysome, Phagosomes, Molecular Cell Biology, Protein biosynthesis, Parasitic Diseases, Animals, Leishmania infantum, Phosphorylation, lcsh:Science, Amastigote, Biology, Leishmaniasis, 030304 developmental biology, Cellular Stress Responses, Regulation of gene expression, 0303 health sciences, Multidisciplinary, biology, Macrophages, lcsh:R, Parasite Physiology, Microbial Growth and Development, Temperature, Gene Expression Regulation, Developmental, Translation (biology), Hydrogen-Ion Concentration, biology.organism_classification, Leishmania, Adaptation, Physiological, Cell biology, Host-Pathogen Interaction, Infectious Diseases, Protein Biosynthesis, Parastic Protozoans, Medicine, lcsh:Q, Parasitology, 030217 neurology & neurosurgery, Research Article |
| الوصف: | The parasitic protozoan Leishmania alternates between an invertebrate and a mammalian host. Upon their entry to mammalian macrophages, Leishmania promastigotes differentiate into amastigote forms within the harsh environment of the phagolysosomal compartment. Here, we provide evidence for the importance of translational control during the Leishmania differentiation process. We find that exposure of promastigotes to a combined elevated temperature and acidic pH stress, a key signal triggering amastigote differentiation, leads to a marked decrease in global translation initiation, which is associated with eIF2α phosphorylation. Interestingly, we show that amastigotes adapted to grow in a cell-free medium exhibit lower levels of protein synthesis in comparison to promastigotes, suggesting that amastigotes have to enter a slow growth state to adapt to the stressful conditions encountered inside macrophages. Reconversion of amastigotes back to promastigote growth results in upregulation of global translation and a decrease in eIF2α phosphorylation. In addition, we show that while general translation is reduced during amastigote differentiation, translation of amastigote-specific transcripts such as A2 is preferentially upregulated. We find that A2 developmental gene regulation is triggered by temperature changes in the environment and that occurs mainly at the level of translation. Upon elevated temperature, the A2 transcript is stabilized through its association with polyribosomes leading to high levels of translation. When temperature decreases during amastigote to promastigote differentiation, the A2 transcript is not longer associated with translating polyribosomes and is being gradually degraded. Overall, these findings contribute to our better understanding of the adaptive responses of Leishmania to stress during its development and highlight the importance of translational control in promastigote to amastigote differentiation and vice-versa. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eaf45d326b410ef435c5a947a81f9cd2Test http://europepmc.org/articles/PMC3365078Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....eaf45d326b410ef435c5a947a81f9cd2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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