IFT25 Links the Signal-Dependent Movement of Hedgehog Components to Intraflagellar Transport

Brian T. Keady, Rajeev Samtani, Kimimasa Tobita, Maiko Tsuchya, Jovenal T. San Agustin, John A. Follit, Julie A. Jonassen, Ramiah Subramanian, Cecilia W. Lo, Gregory J. Pazour

Research output: Contribution to journalArticle

122 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)940-951
Number of pages12
JournalDevelopmental Cell
Volume22
Issue number5
DOIs
StatePublished - May 15 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'IFT25 Links the Signal-Dependent Movement of Hedgehog Components to Intraflagellar Transport'. Together they form a unique fingerprint.

  • Cite this

    Keady, B. T., Samtani, R., Tobita, K., Tsuchya, M., San Agustin, J. T., Follit, J. A., Jonassen, J. A., Subramanian, R., Lo, C. W., & Pazour, G. J. (2012). IFT25 Links the Signal-Dependent Movement of Hedgehog Components to Intraflagellar Transport. Developmental Cell, 22(5), 940-951. https://doi.org/10.1016/j.devcel.2012.04.009