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

Nat Commun. 2015 Sep 18:6:8386. doi: 10.1038/ncomms9386.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Africa, Western
  • Animals
  • Basal Bodies / metabolism*
  • Cilia / metabolism*
  • Ectopic Gene Expression
  • Embryo, Nonmammalian
  • Endothelial Cells / metabolism*
  • Epithelial Cells / metabolism
  • Filamins / metabolism
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • MicroRNAs / genetics*
  • Microscopy, Confocal
  • Monomeric GTP-Binding Proteins / metabolism
  • Nasal Mucosa / cytology
  • Real-Time Polymerase Chain Reaction
  • Xenopus laevis
  • ras Proteins / metabolism*

Substances

  • Actins
  • Filamins
  • MIRN34 microRNA, human
  • MIRN449 microRNA, human
  • MicroRNAs
  • RRAS protein, human
  • Monomeric GTP-Binding Proteins
  • ras Proteins