1. Cell Biology
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A novel Cep120-dependent mechanism inhibits centriole maturation in quiescent cells

  1. Ewelina Betleja
  2. Rashmi Nanjundappa
  3. Tao Cheng
  4. Moe R Mahjoub  Is a corresponding author
  1. Washington University in St Louis, United States
Research Article
  • Cited 11
  • Views 2,161
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Cite this article as: eLife 2018;7:e35439 doi: 10.7554/eLife.35439

Abstract

The two centrioles of the centrosome in quiescent cells are inherently asymmetric structures that differ in age, morphology and function. How these asymmetric properties are established and maintained during quiescence remains unknown. Here we show that a daughter centriole-associated ciliopathy protein, Cep120, plays a critical inhibitory role at daughter centrioles. Depletion of Cep120 in quiescent mouse and human cells causes accumulation of pericentriolar material (PCM) components including Pericentrin, Cdk5Rap2, Ninein and Cep170. The elevated PCM levels result in increased microtubule-nucleation activity at the centrosome. Consequently, loss of Cep120 leads to aberrant dynein-dependent trafficking of centrosomal proteins, dispersal of centriolar satellites, and defective ciliary assembly and signaling. Our results indicate that Cep120 helps to maintain centrosome homeostasis by inhibiting untimely maturation of the daughter centriole, and defines a potentially new molecular defect underlying the pathogenesis of ciliopathies such as Jeune asphyxiating thoracic dystrophy and Joubert syndrome.

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. Ewelina Betleja

    Department of Medicine (Nephrology Division), Washington University in St Louis, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Rashmi Nanjundappa

    Department of Medicine (Nephrology Division), Washington University in St Louis, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3621-4628
  3. Tao Cheng

    Department of Medicine (Nephrology Division), Washington University in St Louis, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Moe R Mahjoub

    Department of Medicine (Nephrology Division), Washington University in St Louis, St Louis, United States
    For correspondence
    mmahjoub@wustl.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8129-7464

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK108005)

  • Moe R Mahjoub

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

Reviewing Editor

  1. Yukiko M Yamashita, University of Michigan, United States

Publication history

  1. Received: January 26, 2018
  2. Accepted: May 6, 2018
  3. Accepted Manuscript published: May 9, 2018 (version 1)
  4. Version of Record published: June 4, 2018 (version 2)

Copyright

© 2018, Betleja 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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