ArticleCommunications biology2022
CLK1/CLK2-driven signalling at the Leishmania kinetochore is captured by spatially referenced proximity phosphoproteomics.
Article in Communications biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 20 citations in OpenAlex.
- Identification of a conserved gene family with an essential role inProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Chemical genetics reveals Leishmania KKT2 and CRK9 kinase activity is required for cell cycle progression.PLoS pathogens · 2026Article
- Specialized RNA decay fine-tunes monogenic antigen expression in Trypanosoma brucei.Nature microbiology · 2026Article
- CRISPR-Cas9 precision editing of kinetochore protein phosphosite codons inFrontiers in cellular and infection microbiology · 2026Article
- Discovery and Characterization of Cell-Permeable Inhibitors ofACS infectious diseases · 2025Article
- Leishmania major chromosomes are replicated from a single high-efficiency locus supplemented by thousands of lower efficiency initiation events.Cell reports · 2025Article
- Characterizing host-microbe interactions with bacterial effector proteins using proximity-dependent biotin identification (BioID).Communications biology · 2025Review
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- ULK4 and Fused/STK36 interact to mediate assembly of a motile flagellum.Molecular biology of the cell · 2023Article
- Divergent polo boxes in KKT2 bind KKT1 to initiate the kinetochore assembly cascade inMolecular biology of the cell · 2022Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Kinetochores in the parasite Leishmania and related kinetoplastids appear to be unique amongst eukaryotes and contain protein kinases as core components. Using the kinetochore kinases KKT2, KKT3 and CLK2 as baits, we developed a BirA* proximity biotinylation methodology optimised for sensitivity, XL-BioID, to investigate the composition and function of the Leishmania kinetochore. We could detect many of the predicted components and also discovered two novel kinetochore proteins, KKT24 and KKT26. Using KKT3 tagged with a fast-acting promiscuous biotin ligase variant, we took proximity biotinylation snapshots of the kinetochore in synchronised parasites. To quantify proximal phosphosites at the kinetochore as the parasite progressed through the cell cycle, we further developed a spatially referenced proximity phosphoproteomics approach. This revealed a group of phosphosites at the kinetochore that were highly dynamic during kinetochore assembly. We show that the kinase inhibitor AB1 targets CLK1/CLK2 (KKT10/KKT19) in Leishmania leading to defective cytokinesis. Using AB1 to uncover CLK1/CLK2 driven signalling pathways important for kinetochore function at G2/M, we found a set of 16 inhibitor responsive kinetochore-proximal phosphosites. Our results exploit new proximity labelling approaches to provide a direct analysis of the Leishmania kinetochore, which is emerging as a promising drug target.
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