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Tubulin tyrosination/detyrosination regulate the affinity and sorting of intraflagellar transport trains on axonemal microtubule doublets

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  • Aditya Chhatre

    (TUD Dresden University of Technology
    Max Planck Institute of Molecular Cell Biology and Genetics
    TUD Dresden University of Technology)

  • Ludek Stepanek

    (Max Planck Institute of Molecular Cell Biology and Genetics
    Czech Academy of Sciences)

  • Adrian Pascal Nievergelt

    (Max Planck Institute of Molecular Cell Biology and Genetics)

  • Gonzalo Alvarez Viar

    (Human Technopole)

  • Stefan Diez

    (TUD Dresden University of Technology
    Max Planck Institute of Molecular Cell Biology and Genetics
    TUD Dresden University of Technology)

  • Gaia Pigino

    (TUD Dresden University of Technology
    Max Planck Institute of Molecular Cell Biology and Genetics
    Human Technopole)

Abstract

Cilia assembly and function rely on the bidirectional transport of components between the cell body and ciliary tip via Intraflagellar Transport (IFT) trains. Anterograde and retrograde IFT trains travel along the B- and A-tubules of microtubule doublets, respectively, ensuring smooth traffic flow. However, the mechanism underlying this segregation remains unclear. Here, we test whether tubulin detyrosination (enriched on B-tubules) and tyrosination (enriched on A-tubules) have a role in IFT logistics. We report that knockout of tubulin detyrosinase VashL in Chlamydomonas reinhardtii causes frequent IFT train stoppages and impaired ciliary growth. By reconstituting IFT train motility on de-membranated axonemes and synthetic microtubules, we show that anterograde and retrograde trains preferentially associate with detyrosinated and tyrosinated microtubules, respectively. We propose that tubulin tyrosination/detyrosination is crucial for spatial segregation and collision-free IFT train motion, highlighting the significance of the tubulin code in ciliary transport.

Suggested Citation

  • Aditya Chhatre & Ludek Stepanek & Adrian Pascal Nievergelt & Gonzalo Alvarez Viar & Stefan Diez & Gaia Pigino, 2025. "Tubulin tyrosination/detyrosination regulate the affinity and sorting of intraflagellar transport trains on axonemal microtubule doublets," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56098-0
    DOI: 10.1038/s41467-025-56098-0
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    References listed on IDEAS

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    1. Ron Orbach & Jonathon Howard, 2019. "The dynamic and structural properties of axonemal tubulins support the high length stability of cilia," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    2. Mohamed A. A. Mohamed & Willi L. Stepp & Zeynep Ökten, 2018. "Reconstitution reveals motor activation for intraflagellar transport," Nature, Nature, vol. 557(7705), pages 387-391, May.
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