Loss of the retrograde motor for IFT disrupts localization of Smo to cilia and prevents the expression of both activator and repressor functions of Gli Academic Article uri icon


MeSH Major

  • Cilia
  • Dyneins
  • Kruppel-Like Transcription Factors
  • Molecular Motor Proteins
  • Nerve Tissue Proteins
  • Receptors, G-Protein-Coupled


  • Sonic Hedgehog (Shh) signals are transduced into nuclear ratios of Gli transcriptional activator versus repressor. The initial part of this process is accomplished by Shh acting through Patched (Ptc) to regulate Smoothened (Smo) activity. The mechanisms by which Ptc regulates Smo, and Smo activity is transduced to processing of Gli proteins remain unclear. Recently, a forward genetic approach in mice identified a role for intraflagellar transport (IFT) genes in Shh signal transduction, downstream of Patched (Ptc) and Rab23. Here, we show that the retrograde motor for IFT is required in the mouse for the phenotypic expression of both Gli activator and repressor function and for effective proteolytic processing of Gli3. Furthermore, we show that the localization of Smo to primary cilia is disrupted in mutants. These data indicate that primary cilia act as specialized signal transduction organelles required for coupling Smo activity to the biochemical processing of Gli3 protein.

publication date

  • November 15, 2005



  • Academic Article



  • eng

Digital Object Identifier (DOI)

  • 10.1016/j.ydbio.2005.08.050

PubMed ID

  • 16229832

Additional Document Info

start page

  • 378

end page

  • 89


  • 287


  • 2