Differentiation granules, a dynamic regulator of T. brucei development
Abstract Adaptation to a change of environment is an essential process for survival, in particular for parasitic organisms exposed to a wide range of hosts. Such adaptations include rapid control of gene expression through the formation of membraneless organelles composed of poly-A RNA and proteins....
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-47309-1 |
| _version_ | 1797219674845347840 |
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| author | Mathieu Cayla Christos Spanos Kirsty McWilliam Eliza Waskett Juri Rappsilber Keith R. Matthews |
| author_facet | Mathieu Cayla Christos Spanos Kirsty McWilliam Eliza Waskett Juri Rappsilber Keith R. Matthews |
| author_sort | Mathieu Cayla |
| collection | DOAJ |
| description | Abstract Adaptation to a change of environment is an essential process for survival, in particular for parasitic organisms exposed to a wide range of hosts. Such adaptations include rapid control of gene expression through the formation of membraneless organelles composed of poly-A RNA and proteins. The African trypanosome Trypanosoma brucei is exquisitely sensitive to well-defined environmental stimuli that trigger cellular adaptations through differentiation events that characterise its complex life cycle. The parasite has been shown to form stress granules in vitro, and it has been proposed that such a stress response could have been repurposed to enable differentiation and facilitate parasite transmission. Therefore, we explored the composition and positional dynamics of membraneless granules formed in response to starvation stress and during differentiation in the mammalian host between the replicative slender and transmission-adapted stumpy forms. We find that T. brucei differentiation does not reflect the default response to environmental stress. Instead, the developmental response of the parasites involves a specific and programmed hierarchy of membraneless granule assembly, with distinct components and regulation by protein kinases such as TbDYRK, that are required for the parasite to successfully progress through its life cycle development and prepare for transmission. |
| first_indexed | 2024-04-24T12:37:24Z |
| format | Article |
| id | doaj.art-866671752bbf4a37af8f1973150e02ad |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-24T12:37:24Z |
| publishDate | 2024-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-866671752bbf4a37af8f1973150e02ad2024-04-07T11:24:40ZengNature PortfolioNature Communications2041-17232024-04-0115111610.1038/s41467-024-47309-1Differentiation granules, a dynamic regulator of T. brucei developmentMathieu Cayla0Christos Spanos1Kirsty McWilliam2Eliza Waskett3Juri Rappsilber4Keith R. Matthews5Institute for Immunology and Infection Research, School of Biological Sciences, University of EdinburghWellcome Centre for Cell Biology, University of EdinburghInstitute for Immunology and Infection Research, School of Biological Sciences, University of EdinburghInstitute for Immunology and Infection Research, School of Biological Sciences, University of EdinburghWellcome Centre for Cell Biology, University of EdinburghInstitute for Immunology and Infection Research, School of Biological Sciences, University of EdinburghAbstract Adaptation to a change of environment is an essential process for survival, in particular for parasitic organisms exposed to a wide range of hosts. Such adaptations include rapid control of gene expression through the formation of membraneless organelles composed of poly-A RNA and proteins. The African trypanosome Trypanosoma brucei is exquisitely sensitive to well-defined environmental stimuli that trigger cellular adaptations through differentiation events that characterise its complex life cycle. The parasite has been shown to form stress granules in vitro, and it has been proposed that such a stress response could have been repurposed to enable differentiation and facilitate parasite transmission. Therefore, we explored the composition and positional dynamics of membraneless granules formed in response to starvation stress and during differentiation in the mammalian host between the replicative slender and transmission-adapted stumpy forms. We find that T. brucei differentiation does not reflect the default response to environmental stress. Instead, the developmental response of the parasites involves a specific and programmed hierarchy of membraneless granule assembly, with distinct components and regulation by protein kinases such as TbDYRK, that are required for the parasite to successfully progress through its life cycle development and prepare for transmission.https://doi.org/10.1038/s41467-024-47309-1 |
| spellingShingle | Mathieu Cayla Christos Spanos Kirsty McWilliam Eliza Waskett Juri Rappsilber Keith R. Matthews Differentiation granules, a dynamic regulator of T. brucei development Nature Communications |
| title | Differentiation granules, a dynamic regulator of T. brucei development |
| title_full | Differentiation granules, a dynamic regulator of T. brucei development |
| title_fullStr | Differentiation granules, a dynamic regulator of T. brucei development |
| title_full_unstemmed | Differentiation granules, a dynamic regulator of T. brucei development |
| title_short | Differentiation granules, a dynamic regulator of T. brucei development |
| title_sort | differentiation granules a dynamic regulator of t brucei development |
| url | https://doi.org/10.1038/s41467-024-47309-1 |
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