1. miR-34/449 control apical actin network formation during multiciliogenesis through small GTPase pathways.
- Author
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Chevalier B, Adamiok A, Mercey O, Revinski DR, Zaragosi LE, Pasini A, Kodjabachian L, Barbry P, and Marcet B
- Subjects
- Africa, Western, Animals, Ectopic Gene Expression, Embryo, Nonmammalian, Epithelial Cells metabolism, Filamins metabolism, Humans, Immunohistochemistry, In Situ Hybridization, Microscopy, Confocal, Monomeric GTP-Binding Proteins metabolism, Nasal Mucosa cytology, Real-Time Polymerase Chain Reaction, Xenopus laevis, Actins metabolism, Basal Bodies metabolism, Cilia metabolism, Endothelial Cells metabolism, MicroRNAs genetics, ras Proteins metabolism
- 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.
- Published
- 2015
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