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IFT25 links the signal-dependent movement of Hedgehog components to intraflagellar transport.

The intraflagellar transport (IFT) system is required for building primary cilia, sensory organelles that cells use to respond to their environment. IFT particles are composed of about 20 proteins, and these proteins are highly conserved across ciliated species. IFT25, however, is absent from some ciliated organisms, suggesting that it may have a unique role distinct from ciliogenesis. Here, we generate an Ift25 null mouse and show that IFT25 is not required for ciliary assembly but is required for proper Hedgehog signaling, which in mammals occurs within cilia. Mutant mice die at birth with multiple phenotypes, indicative of Hedgehog signaling dysfunction. Cilia lacking IFT25 have defects in the signal-dependent transport of multiple Hedgehog components including Patched-1, Smoothened, and Gli2, and fail to activate the pathway upon stimulation. Thus, IFT function is not restricted to building cilia where signaling occurs, but also plays a separable role in signal transduction events.

Pubmed ID: 22595669


  • Keady BT
  • Samtani R
  • Tobita K
  • Tsuchya M
  • San Agustin JT
  • Follit JA
  • Jonassen JA
  • Subramanian R
  • Lo CW
  • Pazour GJ


Developmental cell

Publication Data

May 15, 2012

Associated Grants

  • Agency: NHLBI NIH HHS, Id: 5U01HL098180
  • Agency: NIDDK NIH HHS, Id: DK32520
  • Agency: NIGMS NIH HHS, Id: GM060992
  • Agency: NIGMS NIH HHS, Id: R01 GM060992
  • Agency: NHLBI NIH HHS, Id: U01 HL098180

Mesh Terms

  • Animals
  • Biological Transport
  • Cell Culture Techniques
  • Cilia
  • Flagella
  • Gene Expression Regulation, Developmental
  • Hedgehog Proteins
  • Intracellular Signaling Peptides and Proteins
  • Kruppel-Like Transcription Factors
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Signal Transduction