Cayla, Mathieu orcid.org/0000-0002-3731-7947, McDonald, Lindsay, MacGregor, Paula et al. (1 more author) (2020) An atypical DYRK kinase connects quorum-sensing with posttranscriptional gene regulation in Trypanosoma brucei. eLife. e51620. ISSN 2050-084X
Abstract
The sleeping sickness parasite, Trypanosoma brucei, uses quorum sensing (QS) to balance proliferation and transmission potential in the mammal bloodstream. A signal transduction cascade regulates this process, a component of which is a divergent member of the DYRK family of protein kinases, TbDYRK. Phylogenetic and mutational analysis in combination with activity and phenotypic assays revealed that TbDYRK exhibits a pre-activated confirmation and an atypical HxY activation loop motif, unlike DYRK kinases in other eukaryotes. Phosphoproteomic comparison of TbDYRK null mutants with wild type parasites identified molecules that operate on both the inhibitory 'slender retainer' and activatory 'stumpy inducer' arms of the QS control pathway. One of these molecules, the RNA-regulator TbZC3H20, regulates parasite QS, this being dependent on the integrity of its TbDYRK phosphorylation site. This analysis reveals fundamental differences to conventional DYRK family regulation and links trypanosome environmental sensing, signal transduction and developmental gene expression in a coherent pathway.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 Cayla et al. |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) |
Depositing User: | Pure (York) |
Date Deposited: | 26 Oct 2022 09:50 |
Last Modified: | 16 Oct 2024 18:49 |
Published Version: | https://doi.org/10.7554/eLife.51620 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.7554/eLife.51620 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:192627 |
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Filename: elife_51620_v2.pdf
Description: An atypical DYRK kinase connects quorum-sensing with posttranscriptional gene regulation in Trypanosoma brucei
Licence: CC-BY 2.5