title: IFT25 links the signal-dependent movement of Hedgehog components to intraflagellar transport.
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.
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Keady
authors.forename: Rajeev
authors.initials: R
authors.lastname: Samtani
authors.forename: Kimimasa
authors.initials: K
authors.lastname: Tobita
authors.forename: Maiko
authors.initials: M
authors.lastname: Tsuchya
authors.forename: Jovenal T
authors.initials: JT
authors.lastname: San Agustin
authors.forename: John A
authors.initials: JA
authors.lastname: Follit
authors.forename: Julie A
authors.initials: JA
authors.lastname: Jonassen
authors.forename: Ramiah
authors.initials: R
authors.lastname: Subramanian
authors.forename: Cecilia W
authors.initials: CW
authors.lastname: Lo
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Pazour
mesh_terms: D000818:Animals; D001692:Biological Transport; D018929:Cell Culture Techniques; D002923:Cilia / Q000378:metabolism; D005407:Flagella / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000072086:Smoothened Receptor; D000075746:Zinc Finger Protein Gli2
chemical_list: C000618551:Gli2 protein, mouse; D053823:Hedgehog Proteins; C573939:IFT25 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D051741:Kruppel-Like Transcription Factors; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; C000606240:Ptch1 protein, mouse; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C491022:Smo protein, mouse; D000072086:Smoothened Receptor; D000075746:Zinc Finger Protein Gli2