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A liquid-like organelle at the root of motile ciliopathy

  1. Ryan L Huizar
  2. Chanjae Lee
  3. Alexander A Boulgakov
  4. Amjad Horani
  5. Fan Tu
  6. Edward M Marcotte
  7. Steven L Brody
  8. John B Wallingford  Is a corresponding author
  1. University of Texas at Austin, United States
  2. Washington University School of Medicine, United States
Research Article
  • Cited 9
  • Views 2,417
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Cite this article as: eLife 2018;7:e38497 doi: 10.7554/eLife.38497

Abstract

Motile ciliopathies are characterized by specific defects in cilia beating that result in chronic airway disease, subfertility, ectopic pregnancy, and hydrocephalus. While many patients harbor mutations in the dynein motors that drive cilia beating, the disease also results from mutations in so-called Dynein Axonemal Assembly Factors (DNAAFs) that act in the cytoplasm. The mechanisms of DNAAF action remain poorly defined. Here, we show that DNAAFs concentrate together with axonemal dyneins and chaperones into organelles that form specifically in multiciliated cells, which we term DynAPs, for Dynein Axonemal Particles. These organelles display hallmarks of biomolecular condensates, and remarkably, DynAPs are enriched for the stress granule protein G3bp1, but not for other stress granule proteins or P-body proteins. Finally, we show that both the formation and the liquid-like behaviors of DynAPs are disrupted in a model of motile ciliopathy. These findings provide a unifying cell biological framework for a poorly understood class of human disease genes and add motile ciliopathy to the growing roster of human diseases associated with disrupted biological phase separation.

Article and author information

Author details

  1. Ryan L Huizar

    Department of Molecular Biosciences, University of Texas at Austin, Austin, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Chanjae Lee

    Department of Molecular Biosciences, University of Texas at Austin, Austin, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Alexander A Boulgakov

    Department of Molecular Biosciences, University of Texas at Austin, Austin, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7446-1120
  4. Amjad Horani

    Department of Pediatrics, Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Fan Tu

    Department of Molecular Biosciences, University of Texas at Austin, Austin, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Edward M Marcotte

    Department of Molecular Biosciences, University of Texas at Austin, Austin, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8808-180X
  7. Steven L Brody

    Department of Medicine, Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. John B Wallingford

    Department of Molecular Biosciences, University of Texas at Austin, Austin, United States
    For correspondence
    wallingford@austin.utexas.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6280-8625

Funding

National Heart, Lung, and Blood Institute

  • Ryan L Huizar
  • Chanjae Lee
  • John B Wallingford

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

Ethics

Animal experimentation: Work here was approved by the UT Austin IACUC under protocol numbers: AUP-2015-00160 and AUP-2016-00184.

Reviewing Editor

  1. Anthony A Hyman, Max Planck Institute of Molecular Cell Biology and Genetics, Germany

Publication history

  1. Received: May 19, 2018
  2. Accepted: November 29, 2018
  3. Accepted Manuscript published: December 18, 2018 (version 1)
  4. Version of Record published: January 28, 2019 (version 2)

Copyright

© 2018, Huizar 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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