An atypical DYRK kinase connects quorum-sensing with posttranscriptional gene regulation in <i>Trypanosoma brucei</i>.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32213288.
- Also identified by DOI 10.7554/eLife.51620 and PMC identifier 7136023.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The sleeping sickness parasite, <i>Trypanosoma brucei</i>, 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 conformation 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.
Medical subject headings
- Gene Expression Regulation, Developmental
- Protein Serine-Threonine Kinases
- Protein-Tyrosine Kinases
- Quorum Sensing
- Trypanosoma brucei brucei