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

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.

journal_name

Elife

journal_title

eLife

authors

Huizar RL,Lee C,Boulgakov AA,Horani A,Tu F,Marcotte EM,Brody SL,Wallingford JB

doi

10.7554/eLife.38497

subject

Has Abstract

pub_date

2018-12-18 00:00:00

issn

2050-084X

pii

38497

journal_volume

7

pub_type

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