1. Microbiology and Infectious Disease

An atypical DYRK kinase connects quorum-sensing with posttranscriptional gene regulation in Trypanosoma brucei

  1. Mathieu Cayla
  2. Lindsay McDonald
  3. Paula MacGregor
  4. Keith Matthews  Is a corresponding author
  1. School of Biological Sciences, University of Edinburgh, United Kingdom
  2. University of Cambridge, United Kingdom
https://doi.org/10.7554/eLife.51620
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  1. Mathieu Cayla
  2. Lindsay McDonald
  3. Paula MacGregor
  4. Keith Matthews
(2020)
An atypical DYRK kinase connects quorum-sensing with posttranscriptional gene regulation in Trypanosoma brucei
eLife 9:e51620.
https://doi.org/10.7554/eLife.51620
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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.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Mathieu Cayla

    Institute for Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3731-7947

  2. Lindsay McDonald

    Institute for Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  3. Paula MacGregor

    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0919-3745

  4. Keith Matthews

    Institute for Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom
    For correspondence
    keith.matthews@ed.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0309-9184

Funding

Wellcome (103740/Z14/Z)

  • Keith Matthews

Royal Society (WM140045)

  • Keith Matthews

European Commission (65470)

  • Mathieu Cayla

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Markus Engstler, University of Würzburg, Germany

Ethics

Animal experimentation: Animal experiments in this work were carried out in accordance with the local ethical approval requirements of the University of Edinburgh and the UK Home Office Animal (Scientific Procedures) Act (1986) under licence number 60/4373.

Version history

  1. Received: September 4, 2019
  2. Accepted: March 25, 2020
  3. Accepted Manuscript published: March 26, 2020 (version 1)
  4. Version of Record published: April 6, 2020 (version 2)

Copyright

© 2020, Cayla et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Mathieu Cayla
  2. Lindsay McDonald
  3. Paula MacGregor
  4. Keith Matthews
(2020)
An atypical DYRK kinase connects quorum-sensing with posttranscriptional gene regulation in Trypanosoma brucei
eLife 9:e51620.
https://doi.org/10.7554/eLife.51620

Share this article

https://doi.org/10.7554/eLife.51620

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