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

Benoît Chevalier, Anna Adamiok, Olivier Mercey, Diego R. Revinski, Laure-Emmanuelle Zaragosi, Andrea Pasini, Laurent Kodjabachian, Pascal Barbry () and Brice Marcet ()
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Benoît Chevalier: CNRS, Institut de Pharmacologie Moléculaire et Cellulaire (IPMC)
Anna Adamiok: Aix-Marseille Université, CNRS, UMR7288, Institut de Biologie du Développement de Marseille (IBDM)
Olivier Mercey: CNRS, Institut de Pharmacologie Moléculaire et Cellulaire (IPMC)
Diego R. Revinski: Aix-Marseille Université, CNRS, UMR7288, Institut de Biologie du Développement de Marseille (IBDM)
Laure-Emmanuelle Zaragosi: CNRS, Institut de Pharmacologie Moléculaire et Cellulaire (IPMC)
Andrea Pasini: Aix-Marseille Université, CNRS, UMR7288, Institut de Biologie du Développement de Marseille (IBDM)
Laurent Kodjabachian: Aix-Marseille Université, CNRS, UMR7288, Institut de Biologie du Développement de Marseille (IBDM)
Pascal Barbry: CNRS, Institut de Pharmacologie Moléculaire et Cellulaire (IPMC)
Brice Marcet: CNRS, Institut de Pharmacologie Moléculaire et Cellulaire (IPMC)

Nature Communications, 2015, vol. 6, issue 1, 1-14

Abstract: Abstract 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.

Date: 2015
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DOI: 10.1038/ncomms9386

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