Fort, Cecile;
Walker, Benjamin J;
Baert, Lore;
Wheeler, Richard J;
(2025)
Proteins with proximal-distal asymmetries in axoneme localisation control flagellum beat frequency.
Nature Communications
, 16
, Article 3237. 10.1038/s41467-025-58405-1.
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Abstract
The 9 + 2 microtubule-based axoneme within motile flagella is well known for its symmetry. However, examples of asymmetric structures and proteins asymmetrically positioned within the 9 + 2 axoneme architecture have been identified. These occur in multiple different organisms, particularly involving the inner or outer dynein arms. Here, we comprehensively analyse conserved proximal-distal asymmetries in the uniflagellate trypanosomatid eukaryotic parasites. Building on the genome-wide localisation screen in Trypanosoma brucei we identify conserved proteins with an analogous asymmetric localisation in the related parasite Leishmania mexicana. Using deletion mutants, we find which are necessary for normal cell swimming, flagellum beat parameters and axoneme ultrastructure. Using combinatorial endogenous fluorescent tagging and deletion, we map co-dependencies for assembly into their normal asymmetric localisation. This revealed 15 proteins, 9 known and 6 novel, with a conserved proximal or distal axoneme-specific localisation. Most are outer dynein arm associated and show that there are multiple classes of proximal-distal asymmetry - one which is dependent on the docking complex. Many of these proteins are necessary for retaining the normal frequency of the tip-to-base symmetric flagellar waveform. Our comprehensive mapping reveals unexpected contributions of proximal-specific axoneme components to the frequency of waveforms initiated distally.
| Type: | Article |
|---|---|
| Title: | Proteins with proximal-distal asymmetries in axoneme localisation control flagellum beat frequency |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41467-025-58405-1 |
| Publisher version: | https://doi.org/10.1038/s41467-025-58405-1 |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Flagella, Axoneme, Trypanosoma brucei brucei, Protozoan Proteins, Leishmania mexicana, Dyneins |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Mathematics |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10207499 |
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