IFT25 Links the Signal-Dependent Movement of Hedgehog Components to Intraflagellar Transport
Open accessAbstract
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.
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The IFT-B complex proteins IFT25 and IFT27 are involved in ciliary export of hedgehog signalling components via retrograde IFT.
“whereas the IFT-B complex proteins IFT25 and IFT27 are involved in ciliary export of hedgehog (HH) signalling components via retrograde IFT 59, 60, 62, 63.”
From Cellular signalling by primary cilia in development, organ function and disease (2019) · cites this paper as [60]
The Introduction and Discussion report that IFT25 is required for ciliary export of the Hedgehog components Ptch1 and Smo. The Results show that IFT27 is depleted from cilia lacking IFT25, but the Discussion says IFT27’s contribution remains unclear. The paper presents export through IFT as a model, rather than directly establishing that both proteins mediate it via retrograde IFT. Page numbers were not available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredEarly work using Chlamydomonas and C. elegans mutants suggested IFT-A and IFT-B function in retrograde and anterograde IFT, respectively, but these polypeptides are now known to participate in ciliary transport in both directions.
“For example, although early work using C. reinhardtii and C. elegans mutants suggested that IFT-A and IFT-B complexes function in retrograde and anterograde IFT, respectively 30, 46, we now know that these polypeptides participate in ciliary transport in both directions 54–60.”
From Cellular signalling by primary cilia in development, organ function and disease (2019) · cites this paper as [60]
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References 49 · Cited by 216
- Authors
- 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.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- University of Pittsburgh (US)
- Corresponding author
- Pazour, Gregory J.
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2012-05
- Volume
- 22
- Issue
- 5
- Pages
- 940-951
- ISSN
- 1534-5807 (ISSN-L)
- PMC
- PMC3366633
- OpenAlex
- W1997628120
- Cited by
- 216
- References
- 49
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 9 · 2023: 13 · 2022: 12 · 2021: 18 · 2020: 21 · 2019: 14 · 2018: 17 · 2017: 17 · 2016: 16 · 2015: 21 · 2014: 21 · 2013: 18 · 2012: 6
- FWCI
- 12.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5U01HL098180, GM060992)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Keywords
- intraflagellar transport, Hedgehog signaling, primary cilia, Patched1, Smoothened, GLI2, ciliogenesis, signal transduction
- MeSH terms
- Patched Receptors, Patched-1 Receptor, Smoothened Receptor, Zinc Finger Protein Gli2, Animals, Biological Transport, Cilia, Flagella, Mice, Inbred C57BL, Receptors, Cell Surface, Signal Transduction, Mice, Knockout, Gene Expression Regulation, Developmental, Cell Culture Techniques, Receptors, G-Protein-Coupled, Intracellular Signaling Peptides and Proteins, Mice, Kruppel-Like Transcription Factors, Hedgehog Proteins
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