Differentiation granules, a dynamic regulator of T. brucei development

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 Afri...

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Published in:	Nature communications Vol. 15; no. 1; p. 2972
Main Authors:	Cayla, Mathieu, Spanos, Christos, McWilliam, Kirsty, Waskett, Eliza, Rappsilber, Juri, Matthews, Keith R.
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 06-04-2024 Nature Publishing Group Nature Portfolio
Subjects:	13/1 13/106 13/109 13/95 14 14/35 14/63 38/77 631/136/142 631/326/417/1716 631/326/417/2549 631/80/642 631/80/86/2366 64/60 82/58 Adaptation Animals Differentiation Environmental changes Environmental effects Environmental stress Gene expression Granular materials Humanities and Social Sciences Kinases Life cycles Mammals multidisciplinary Nutrient deficiency Organelles Parasites Proteins Protozoa Science Science (multidisciplinary) Trypanosoma Trypanosoma brucei Trypanosoma brucei brucei - genetics Trypanosoma brucei brucei - metabolism Trypanosome
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Summary:	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. The African trypanosome Trypanosoma brucei has been shown to form stress granules in vitro that might be repurposed to enable differentiation and facilitate parasite transmission. Here, Cayla et al. show that differentiation between slender and stumpy forms does involve membrane-less granules that are different from nutritional stress granules.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-024-47309-1