1. Cell Biology
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TRIM37 prevents formation of centriolar protein assemblies by regulating Centrobin

  1. Fernando R Balestra  Is a corresponding author
  2. Andrés Domínguez-Calvo
  3. Benita Wolf
  4. Coralie Busso
  5. Alizée Buff
  6. Tessa Averink
  7. Marita Lipsanen-Nyman
  8. Pablo Huertas
  9. Rosa M Ríos
  10. Pierre Gönczy  Is a corresponding author
  1. CABIMER-University of Seville, Spain
  2. Swiss Federal Institute of Technology, Switzerland
  3. University of Helsinki, Finland
Research Article
  • Cited 2
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Cite this article as: eLife 2021;10:e62640 doi: 10.7554/eLife.62640

Abstract

TRIM37 is an E3 ubiquitin ligase mutated in Mulibrey nanism, a disease with impaired organ growth and increased tumor formation. TRIM37 depletion from tissue culture cells results in supernumerary foci bearing the centriolar protein Centrin. Here, we characterize these centriolar protein assemblies (Cenpas) to uncover the mechanism of action of TRIM37. We find that an atypical de novo assembly pathway can generate Cenpas that act as microtubule organizing centers (MTOCs), including in Mulibrey patient cells. Correlative light electron microscopy reveals that Cenpas are centriole-related or electron-dense structures with stripes. TRIM37 regulates the stability and solubility of Centrobin, which accumulates in elongated entities resembling the striped electron dense structures upon TRIM37 depletion. Furthermore, Cenpas formation upon TRIM37 depletion requires PLK4, as well as two parallel pathways relying respectively on Centrobin and PLK1. Overall, our work uncovers how TRIM37 prevents Cenpas formation, which would otherwise threaten genome integrity, including in Mulibrey patients.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Fernando R Balestra

    Genome Biology Department, CABIMER-University of Seville, Seville, Spain
    For correspondence
    fernando.balestra@cabimer.es
    Competing interests
    The authors declare that no competing interests exist.
  2. Andrés Domínguez-Calvo

    Genome Biology Department, CABIMER-University of Seville, Seville, Spain
    Competing interests
    The authors declare that no competing interests exist.
  3. Benita Wolf

    Swiss Institute for Experimental Cancer Research, School of Life Sciences, Swiss Federal Institute of Technology, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5673-4239
  4. Coralie Busso

    Swiss Institute of Experimental Cancer Research, Swiss Federal Institute of Technology, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  5. Alizée Buff

    Swiss Institute for Experimental Cancer Research, School of Life Sciences, Swiss Federal Institute of Technology, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  6. Tessa Averink

    Swiss Institute for Experimental Cancer Research, School of Life Sciences, Swiss Federal Institute of Technology, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  7. Marita Lipsanen-Nyman

    Children's Hospital, University of Helsinki, Helsinki, Finland
    Competing interests
    The authors declare that no competing interests exist.
  8. Pablo Huertas

    Genome Biology Department, CABIMER-University of Seville, Seville, Spain
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1756-4449
  9. Rosa M Ríos

    Cell Dynamics and Signalling, CABIMER-University of Seville, Seville, Spain
    Competing interests
    The authors declare that no competing interests exist.
  10. Pierre Gönczy

    Swiss Institute of Experimental Cancer Research, Swiss Federal Institute of Technology, Lausanne, Switzerland
    For correspondence
    pierre.gonczy@epfl.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6305-6883

Funding

Krebsforschung Schweiz (KFS-3388-02-2014)

  • Pierre Gönczy

Marie Curie Actions (PIEF-GA-2013-629414)

  • Fernando R Balestra

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

Ethics

Human subjects: Fibroblast cultures were established from skin biopsy samples with approval by the Institutional Review Board of the Helsinki University Central Hospital (183/13/03/03/2009). The patients signed an informed consent for the use of fibroblast cultures.

Reviewing Editor

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

Publication history

  1. Received: September 2, 2020
  2. Accepted: January 22, 2021
  3. Accepted Manuscript published: January 25, 2021 (version 1)
  4. Version of Record published: February 8, 2021 (version 2)

Copyright

© 2021, Balestra 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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