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XB-ART-55552
Elife January 1, 2018; 7

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

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


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.

PubMed ID: 30561330
PMC ID: PMC6349401
Article link: Elife
Grant support: [+]
Genes referenced: armc4 ccdc63 cetn4 dcp1a dnaaf2 dnaaf3 dnaaf4 dnaaf5 dnai1 dnai2 dnajc7 dnal4 dnali1 eea1 foxj1 foxj1.2 fus g3bp1 galt hsp90ab1 hspa8 lrrc6 lsm4 mcc mcidas mns1 mtor nme5 pih1d3 rsph1 ruvbl1 ruvbl2 spag1 stip1 tia1 ttc25 ttc9c tuba4b wdr78 zmynd10
GO keywords: cilium movement [+]
Antibodies: Tuba4b Ab5
Morpholinos: dnaaf5 MO1 dnaaf5 MO2 dnaaf5 MO3 dnaaf5 MO4

Disease Ontology terms: primary ciliary dyskinesia 1
OMIMs: CILIARY DYSKINESIA, PRIMARY, 1; CILD1

Article Images: [+] show captions


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