Format

Send to

Choose Destination
Elife. 2018 Dec 18;7. pii: e38497. doi: 10.7554/eLife.38497.

A liquid-like organelle at the root of motile ciliopathy.

Author information

1
Department of Molecular Biosciences, University of Texas, Austin, United States.
2
Department of Pediatrics, Washington University School of Medicine, St Louis, United States.
3
Department of Medicine, Washington University School of Medicine, St Louis, United States.
#
Contributed equally

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.

KEYWORDS:

DynAP; cell biology; chaperone; cilia; dynein; heat shock protein; primary ciliary dyskinesia; xenopus

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center