A liquid-like organelle at the root of motile ciliopathy
- University of Texas at Austin, United States
- Washington University School of Medicine, United States
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.
Data availability
Software has been deposited to GitHub (https://github.com/marcottelab/FociFinder3D) and image data will be uploaded to Dryad.
Article and author information
Author details
Alexander A Boulgakov
John B Wallingford
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.
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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A liquid-like organelle at the root of motile ciliopathy
eLife 7:e38497.
https://doi.org/10.7554/eLife.38497
