Actin remodelling factors control ciliogenesis by regulating YAP/TAZ activity and vesicle trafficking

Nat Commun. 2015 Apr 7;6:6781. doi: 10.1038/ncomms7781.

Abstract

Primary cilia exert a profound impact on cell signalling and cell cycle progression. Recently, actin cytoskeleton destabilization has been recognized as a dominant inducer of ciliogenesis, but the exact mechanisms regulating ciliogenesis remain poorly understood. Here we show that the actin cytoskeleton remodelling controls ciliogenesis by regulating transcriptional coactivator YAP/TAZ as well as ciliary vesicle trafficking. Cytoplasmic retention of YAP/TAZ correlates with active ciliogenesis either in spatially confined cells or in cells treated with an actin filament destabilizer. Moreover, knockdown of YAP/TAZ is sufficient to induce ciliogenesis, whereas YAP/TAZ hyperactivation suppresses serum starvation-mediated ciliogenesis. We also identify actin remodelling factors LIMK2 and TESK1 as key players in the ciliogenesis control network in which YAP/TAZ and directional vesicle trafficking are integral components. Our work provides new insights for understanding the link between actin dynamics and ciliogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism*
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Blotting, Western
  • Cell Line
  • Cilia / metabolism*
  • Clathrin-Coated Vesicles / metabolism*
  • Fluorescent Antibody Technique
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Lim Kinases / metabolism
  • Microscopy, Fluorescence
  • Phosphoproteins / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism
  • Transcription Factors
  • Transcriptional Activation

Substances

  • Adaptor Proteins, Signal Transducing
  • Intracellular Signaling Peptides and Proteins
  • Phosphoproteins
  • Transcription Factors
  • WWTR1 protein, human
  • YAP1 (Yes-associated) protein, human
  • testis-specific protein kinase 1
  • LIMK2 protein, human
  • Lim Kinases
  • Protein-Serine-Threonine Kinases