Differentiation granules, a dynamic regulator of T. brucei development

Mathieu Cayla (), Christos Spanos, Kirsty McWilliam, Eliza Waskett, Juri Rappsilber and Keith R. Matthews
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Mathieu Cayla: University of Edinburgh
Christos Spanos: University of Edinburgh
Kirsty McWilliam: University of Edinburgh
Eliza Waskett: University of Edinburgh
Juri Rappsilber: University of Edinburgh
Keith R. Matthews: University of Edinburgh

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-47309-1

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