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

eLife

Keith Matthews¹  Lindsay McDonald¹  Mathieu Cayla¹  Paula MacGregor¹ 

[1] Institute for Immunology and Infection Research, School of Biological Sciences, Charlotte Auerbach Road, University of Edinburgh, Edinburgh, United Kingdom;

关键词: parasite;    Trypanosoma;    differentiation;    DYRK;    protein kinase;    gene expression;    None;   

DOI  :  10.7554/eLife.51620

来源: publisher

【 摘 要 】

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 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.

【 授权许可】

CC BY