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FAP106 is an interaction hub for assembling microtubule inner proteins at the cilium inner junction

Author

Listed:
  • Michelle M. Shimogawa

    (University of California Los Angeles)

  • Angeline S. Wijono

    (University of California Los Angeles)

  • Hui Wang

    (University of California Los Angeles
    University of California Los Angeles
    University of California Los Angeles)

  • Jiayan Zhang

    (University of California Los Angeles
    University of California Los Angeles
    University of California Los Angeles)

  • Jihui Sha

    (University of California Los Angeles)

  • Natasha Szombathy

    (University of California Los Angeles)

  • Sabeeca Vadakkan

    (University of California Los Angeles)

  • Paula Pelayo

    (University of California Los Angeles)

  • Keya Jonnalagadda

    (University of California Los Angeles)

  • James Wohlschlegel

    (University of California Los Angeles)

  • Z. Hong Zhou

    (University of California Los Angeles
    University of California Los Angeles
    University of California Los Angeles)

  • Kent L. Hill

    (University of California Los Angeles
    University of California Los Angeles
    University of California Los Angeles)

Abstract

Motility of pathogenic protozoa depends on flagella (synonymous with cilia) with axonemes containing nine doublet microtubules (DMTs) and two singlet microtubules. Microtubule inner proteins (MIPs) within DMTs influence axoneme stability and motility and provide lineage-specific adaptations, but individual MIP functions and assembly mechanisms are mostly unknown. Here, we show in the sleeping sickness parasite Trypanosoma brucei, that FAP106, a conserved MIP at the DMT inner junction, is required for trypanosome motility and functions as a critical interaction hub, directing assembly of several conserved and lineage-specific MIPs. We use comparative cryogenic electron tomography (cryoET) and quantitative proteomics to identify MIP candidates. Using RNAi knockdown together with fitting of AlphaFold models into cryoET maps, we demonstrate that one of these candidates, MC8, is a trypanosome-specific MIP required for parasite motility. Our work advances understanding of MIP assembly mechanisms and identifies lineage-specific motility proteins that are attractive targets to consider for therapeutic intervention.

Suggested Citation

  • Michelle M. Shimogawa & Angeline S. Wijono & Hui Wang & Jiayan Zhang & Jihui Sha & Natasha Szombathy & Sabeeca Vadakkan & Paula Pelayo & Keya Jonnalagadda & James Wohlschlegel & Z. Hong Zhou & Kent L., 2023. "FAP106 is an interaction hub for assembling microtubule inner proteins at the cilium inner junction," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40230-z
    DOI: 10.1038/s41467-023-40230-z
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    References listed on IDEAS

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