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PreprintCited by 25Genetic and Kidney Cyst DiseasesMicrotubule and mitosis dynamicsCystic Fibrosis Research Advances

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Structure of the ciliary tip central pair reveals the unique role of the microtubule-seam binding protein SPEF1

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Legal, Thibault, Joachimiak, Ewa, Parra, Mireya, Peng, Wang, Tam, Amanda, Black, Corbin, Valente-Paterno, Melissa, Brouhard, Gary, Gaertig, Jacek, Wloga, Dorota, Bui, Khanh Huy·2024·Current Biology
DOI 10.1101/2024.12.02.626492PMC PMC12258958

Preprint — published as 10.1016/j.cub.2025.06.020

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Abstract

Motile cilia are unique organelles with the ability to autonomously move. Force generated by beating cilia propels cells and moves fluids. The ciliary skeleton is made of peripheral doublet microtubules and a central pair (CP) with a distinct structure at the tip. In this study, we present a high-resolution structure of the CP in the ciliary tip of the ciliate Tetrahymena thermophila and identify several tip proteins that bind and form unique patterns on both microtubules of the tip CP. Two of those proteins that contain tubulin polymerization-promoting protein (TPPP)-like domains, TLP1 and TLP2, bind to high curvature regions of the microtubule. TLP2, which contains two TPPP-like domains, is an unusually long protein that wraps laterally around half a microtubule and forms the bridge between the two microtubules. Moreover, we found that the conserved protein SPEF1 binds to both microtubule seams. In vitro , human SPEF1 not only binds to the microtubule seam but also crosslinks two parallel microtubules. Single-molecule microtubule dynamics assays indicate that SPEF1 stabilizes microtubules in vitro . Together, these data show that the proteins in the tip CP maintain stable microtubule structure and probably play important roles in maintaining the integrity of the axoneme.

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Metadata

Authors
Legal, T., Joachimiak, E., Parra, M., Peng, W., Tam, A., Black, C., Valente-Paterno, M., Brouhard, G., Gaertig, J., Wloga, D., & Bui, K. H.
Affiliations
  • McGill University (CA)
  • Instytut Biologii Doświadczalnej im. Marcelego Nenckiego (PL)
  • University of Georgia (US)
Corresponding author
Bui, Khanh Huy
ORCID
Venue
Current Biology
Publisher
openRxiv
Published
2024-12-04
Volume
35
Issue
14
Pages
3404-3417.e6
ISSN
0960-9822 (ISSN-L)
DOI
10.1101/2024.12.02.626492
PMC
PMC12258958
OpenAlex
W4412391696
Cited by
25
References
1
Citations by year
2026: 16 · 2025: 9
FWCI
6.63
Type
journal article
Language
en
Open access
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Locations
  • Current Biology (acceptedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
Funders
  • McGill University
  • Fonds Québécois de la Recherche sur la Nature et les Technologies
  • National Institutes of Health
  • Canadian Institutes of Health Research (156354_1)
  • Natural Sciences and Engineering Research Council of Canada (04774, rgpin-2022-04774)
  • Fonds de Recherche du Québec - Santé (353841)
  • Fonds de recherche du Québec – Nature et technologies (345547)
  • National Institute of General Medical Sciences (R01GM135444)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
Keywords
central pair, axoneme, Tetrahymena thermophila, microtubule stabilization, ciliary motility, cryo-electron tomography, subtomogram averaging

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