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XB-ART-55292
Dev Cell January 1, 2018; 46 (5): 595-610.e3.

WDR5 Stabilizes Actin Architecture to Promote Multiciliated Cell Formation.

Kulkarni SS , Griffin JN , Date PP , Liem KF , Khokha MK .


Abstract
The actin cytoskeleton is critical to shape cells and pattern intracellular organelles, which collectively drives tissue morphogenesis. In multiciliated cells (MCCs), apical actin drives expansion of the cell surface necessary to host hundreds of cilia. The apical actin also forms a lattice to uniformly distribute basal bodies. This apical actin network is dynamically remodeled, but the molecules that regulate its architecture remain poorly understood. We identify the chromatin modifier, WDR5, as a regulator of apical F-actin in MCCs. Unexpectedly in MCCs, WDR5 has a function independent of chromatin modification. We discover a scaffolding role for WDR5 between the basal body and F-actin. Specifically, WDR5 binds to basal bodies and migrates apically, where F-actin organizes around WDR5. Using a monomer trap for G-actin, we show that WDR5 stabilizes F-actin to maintain lattice architecture. In summary, we identify a non-chromatin role for WDR5 in stabilizing F-actin in MCCs.

PubMed ID: 30205038
PMC ID: PMC6177229
Article link: Dev Cell
Grant support: [+]
Genes referenced: atp6v1a dnah9 foxj1 foxj1.2 gapdh itln1 mcc mcidas rfx2 rpe tuba4b tubg1 utrn wdr5
GO keywords: ciliary basal body organization [+]
Antibodies: Tuba4b Ab5 Tubg1 Ab4 actin Ab1 wdr5 Ab1
Morpholinos: wdr5 MO4 wdr5 MO5

Disease Ontology terms: visceral heterotaxy [+]

Article Images: [+] show captions
References:
Ang, 2011, Pubmed [+]


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