ArticleProceedings of the National Academy of Sciences of the United States of America2018
FGFR1-mediated protocadherin-15 loading mediates cargo specificity during intraflagellar transport in inner ear hair-cell kinocilia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- Role of Pcdh15 in the development of intrinsic polarity of inner ear hair cells.PLoS genetics · 2025Article
- FGFR2 residence in primary cilia is necessary for epithelial cell signaling.The Journal of cell biology · 2025Article
- Isolation and Comprehensive Analysis of Cochlear Tissue-Derived Small Extracellular Vesicles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Stepwise fate conversion of supporting cells to sensory hair cells in the chick auditory epithelium.iScience · 2023Article
- An EMT-primary cilium-GLIS2 signaling axis regulates mammogenesis and claudin-low breast tumorigenesis.Science advances · 2021Article
- Review
- Cilia in the developing zebrafish ear.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2020Review
- Initiation of Supporting Cell Activation for Hair Cell Regeneration in the Avian Auditory Epithelium: An Explant Culture Model.Frontiers in cellular neuroscience · 2020Article
- New insights into regulation and function of planar polarity in the inner ear.Neuroscience letters · 2019Review
- Fibroblast growth factor receptor influences primary cilium length through an interaction with intestinal cell kinase.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
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Authors and funding
9 authors at 5 institutions in 4 countries.
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Abstract
The mechanosensory hair cells of the inner ear are required for hearing and balance and have a distinctive apical structure, the hair bundle, that converts mechanical stimuli into electrical signals. This structure comprises a single cilium, the kinocilium, lying adjacent to an ensemble of actin-based projections known as stereocilia. Hair bundle polarity depends on kinociliary protocadherin-15 (Pcdh15) localization. Protocadherin-15 is found only in hair-cell kinocilia, and is not localized to the primary cilia of adjacent supporting cells. Thus, Pcdh15 must be specifically targeted and trafficked into the hair-cell kinocilium. Here we show that kinocilial Pcdh15 trafficking relies on cell type-specific coupling to the generic intraflagellar transport (IFT) transport mechanism. We uncover a role for fibroblast growth factor receptor 1 (FGFR1) in loading Pcdh15 onto kinociliary transport particles in hair cells. We find that on activation, FGFR1 binds and phosphorylates Pcdh15. Moreover, we find a previously uncharacterized role for clathrin in coupling this kinocilia-specific cargo with the anterograde IFT-B complex through the adaptor, DAB2. Our results identify a modified ciliary transport pathway used for Pcdh15 transport into the cilium of the inner ear hair cell and coordinated by FGFR1 activity.
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