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Nat Commun September 18, 2015; 6 8386.

miR-34/449 control apical actin network formation during multiciliogenesis through small GTPase pathways.

Chevalier B , Adamiok A , Mercey O , Revinski DR , Zaragosi LE , Pasini A , Kodjabachian L , Barbry P , Marcet B .

Vertebrate multiciliated cells (MCCs) contribute to fluid propulsion in several biological processes. We previously showed that microRNAs of the miR-34/449 family trigger MCC differentiation by repressing cell cycle genes and the Notch pathway. Here, using human and Xenopus MCCs, we show that beyond this initial step, miR-34/449 later promote the assembly of an apical actin network, required for proper basal bodies anchoring. Identification of miR-34/449 targets related to small GTPase pathways led us to characterize R-Ras as a key regulator of this process. Protection of RRAS messenger RNA against miR-34/449 binding impairs actin cap formation and multiciliogenesis, despite a still active RhoA. We propose that miR-34/449 also promote relocalization of the actin binding protein Filamin-A, a known RRAS interactor, near basal bodies in MCCs. Our study illustrates the intricate role played by miR-34/449 in coordinating several steps of a complex differentiation programme by regulating distinct signalling pathways.

PubMed ID: 26381333
PMC ID: PMC4595761
Article link: Nat Commun

Species referenced: Xenopus laevis
Genes referenced: arhgap1 arhgdib gnl3 igf2bp3 mcc mcidas mmut notch1 odc1 rho rho.2 rhoa rras tcirg1 tub
Morpholinos: dll1 miR-449 protector MO1 dll1 miR-449 protector MO2 miR-449 MO1 miR-449 MO2 miR-449 MO3 rras MO1 rras miR-449 protector MO

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References [+] :
Ada-Nguema, The small GTPase R-Ras regulates organization of actin and drives membrane protrusions through the activity of PLCepsilon. 2006, Pubmed