Evolutionary conservation of centriole rotational asymmetry in the human centrosome

  1. Noémie Gaudin
  2. Paula Martin Gil
  3. Meriem Boumendjel
  4. Dmitry Ershov
  5. Catherine Pioche-Durieu
  6. Manon Bouix
  7. Quentin Delobelle
  8. Lucia Maniscalco
  9. Than Bich Ngan Phan
  10. Vincent Heyer
  11. Bernardo Reina-San-Martin
  12. Juliette Azimzadeh  Is a corresponding author
  1. Institut Jacques Monod, France
  2. Institut Pasteur, USR 3756 CNRS, France
  3. Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), France

Abstract

Centrioles are formed by microtubule triplets in a nine-fold symmetric arrangement. In flagellated protists and in animal multiciliated cells, accessory structures tethered to specific triplets render the centrioles rotationally asymmetric, a property that is key to cytoskeletal and cellular organization in these contexts. In contrast, centrioles within the centrosome of animal cells display no conspicuous rotational asymmetry. Here, we uncover rotationally asymmetric molecular features in human centrioles. Using ultrastructure expansion microscopy, we show that LRRCC1, the ortholog of a protein originally characterized in flagellate green algae, associates preferentially to two consecutive triplets in the distal lumen of human centrioles. LRRCC1 partially co-localizes and affects the recruitment of another distal component, C2CD3, which also has an asymmetric localization pattern in the centriole lumen. Together, LRRCC1 and C2CD3 delineate a structure reminiscent of a filamentous density observed by electron microscopy in flagellates, termed the 'acorn'. Functionally, the depletion of LRRCC1 in human cells induced defects in centriole structure, ciliary assembly and ciliary signaling, supporting that LRRCC1 cooperates with C2CD3 to organizing the distal region of centrioles. Since a mutation in the LRRCC1 gene has been identified in Joubert syndrome patients, this finding is relevant in the context of human ciliopathies. Taken together, our results demonstrate that rotational asymmetry is an ancient property of centrioles that is broadly conserved in human cells. Our work also reveals that asymmetrically localized proteins are key for primary ciliogenesis and ciliary signaling in human cells.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files are available from the Dryad database (doi:10.5061/dryad.95x69p8m5).

The following data sets were generated

Article and author information

Author details

  1. Noémie Gaudin

    Institut Jacques Monod, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Paula Martin Gil

    Institut Jacques Monod, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Meriem Boumendjel

    Institut Jacques Monod, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Dmitry Ershov

    Département Biologie Computationnelle, Institut Pasteur, USR 3756 CNRS, France, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Catherine Pioche-Durieu

    Institut Jacques Monod, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0988-1169
  6. Manon Bouix

    Institut Jacques Monod, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Quentin Delobelle

    Institut Jacques Monod, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Lucia Maniscalco

    Institut Jacques Monod, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  9. Than Bich Ngan Phan

    Institut Jacques Monod, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  10. Vincent Heyer

    Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Ilkirch, France
    Competing interests
    The authors declare that no competing interests exist.
  11. Bernardo Reina-San-Martin

    Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Ilkirch, France
    Competing interests
    The authors declare that no competing interests exist.
  12. Juliette Azimzadeh

    Institut Jacques Monod, Paris, France
    For correspondence
    juliette.azimzadeh@ijm.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7292-9973

Funding

Agence Nationale de la Recherche (ANR-21-CE13-008)

  • Juliette Azimzadeh

Fondation pour la Recherche Médicale (Graduate Student Fellowship)

  • Noémie Gaudin

Fondation ARC pour la Recherche sur le Cancer (Dotation)

  • Juliette Azimzadeh

Ligue Contre le Cancer (Dotation)

  • Juliette Azimzadeh

Labex Who Am I?

  • Juliette Azimzadeh

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Jens Lüders, Institute for Research in Biomedicine, Spain

Version history

  1. Received: July 21, 2021
  2. Preprint posted: July 22, 2021 (view preprint)
  3. Accepted: March 22, 2022
  4. Accepted Manuscript published: March 23, 2022 (version 1)
  5. Version of Record published: April 5, 2022 (version 2)

Copyright

© 2022, Gaudin et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Noémie Gaudin
  2. Paula Martin Gil
  3. Meriem Boumendjel
  4. Dmitry Ershov
  5. Catherine Pioche-Durieu
  6. Manon Bouix
  7. Quentin Delobelle
  8. Lucia Maniscalco
  9. Than Bich Ngan Phan
  10. Vincent Heyer
  11. Bernardo Reina-San-Martin
  12. Juliette Azimzadeh
(2022)
Evolutionary conservation of centriole rotational asymmetry in the human centrosome
eLife 11:e72382.
https://doi.org/10.7554/eLife.72382

Share this article

https://doi.org/10.7554/eLife.72382

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