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The kinesin-4 protein Kif7 regulates mammalian Hedgehog signalling by organizing the cilium tip compartment
Open accessAbstract
Mammalian Hedgehog (Hh) signal transduction requires a primary cilium, a microtubule-based organelle, and the Gli-Sufu complexes that mediate Hh signalling, which are enriched at cilia tips. Kif7, a kinesin-4 family protein, is a conserved regulator of the Hh signalling pathway and a human ciliopathy protein. Here we show that Kif7 localizes to the cilium tip, the site of microtubule plus ends, where it limits cilium length and controls cilium structure. Purified recombinant Kif7 binds the plus ends of growing microtubules in vitro, where it reduces the rate of microtubule growth and increases the frequency of microtubule catastrophe. Kif7 is not required for normal intraflagellar transport or for trafficking of Hh pathway proteins into cilia. Instead, a central function of Kif7 in the mammalian Hh pathway is to control cilium architecture and to create a single cilium tip compartment, where Gli-Sufu activity can be correctly regulated.
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“β-arrestins are adaptor proteins that are recruited to the proximal C-terminus of GPR161 in a manner dependent on G protein-coupled receptor kinase 2 (GRK2)138.”
From Cellular signalling by primary cilia in development, organ function and disease (2019) · cites this paper as [138]
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“GPR161 is also removed from primary cilia in a SMO-dependent and β-arrestin-dependent manner following activation of HH signalling 28, 138.”
From Cellular signalling by primary cilia in development, organ function and disease (2019) · cites this paper as [138]
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Control of microtubule organization and dynamics: Two ends in the limelight
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“Kinesin-4 motors typically show plus-end-directed motility, with the exception of the non-motile ciliary regulator kinesin-like 7 (KIF7), which mildly promotes, rather than suppresses, catastrophes and is involved in limiting the length of axonemal microtubules 39 .”
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“In response to Hh activation, Kif7 localizes to the tip of the PC, and it can control the cilium structure and organize a specialized compartment necessary for Hh signaling [85].”
BackgroundPrimary Cilia and Mammalian Hedgehog Signaling
Bangs, F., & Anderson, K. V. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a028175 · Cited by 642
“The tip compartment of the primary cilium is organized, at least in part, by KIF7, an evolutionarily conserved core component of the Hh pathway (He et al. 2014).”
BackgroundInfluentialSelf-citationEstablishing and regulating the composition of cilia for signal transduction
Nachury, M. V., & Mick, D. U. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0116-4 · Cited by 397
Metadata
- Authors
- He, M., Subramanian, R., Bangs, F., Omelchenko, T., Liem Jr, K. F., Kapoor, T. M., & Anderson, K. V.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Rockefeller University (US)
- Corresponding author
- Anderson, Kathryn V.
- Venue
- Nature Cell Biology
- Published
- 2014-06-22
- Volume
- 16
- Issue
- 7
- Pages
- 663-672
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC4085576
- OpenAlex
- W2083616180
- Cited by
- 302
- References
- 55
- Citations by year
- 2026: 14 · 2025: 20 · 2024: 20 · 2023: 13 · 2022: 30 · 2021: 26 · 2020: 26 · 2019: 27 · 2018: 31 · 2017: 34 · 2016: 22 · 2015: 32 · 2014: 7
- FWCI
- 20.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (P30CA008748)
- National Institute of General Medical Sciences (R01GM065933, GM65933)
- National Institute of Neurological Disorders and Stroke (NS044385, R01NS044385)
- 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
- KIF7, kinesin-4, Hedgehog signaling, primary cilia, microtubule plus ends, ciliopathies, intraflagellar transport, ciliary trafficking
- MeSH terms
- Animals, Cell Line, Cells, Cultured, Cilia, Fibroblasts, Humans, Microtubules, Mutation, Protein Binding, Recombinant Proteins, Signal Transduction, Kinesins, Protein Transport, NIH 3T3 Cells, Mice, Hedgehog Proteins, Axoneme, HEK293 Cells
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