Reconstitution reveals motor activation for intraflagellar transport
Open accessAbstract
The human body represents a notable example of ciliary diversification. Extending from the surface of most cells, cilia accomplish a diverse set of tasks. Predictably, mutations in ciliary genes cause a wide range of human diseases such as male infertility and blindness. In Caenorhabditis elegans sensory cilia, this functional diversity appears to be traceable to the differential regulation of the kinesin-2-powered intraflagellar-transport (IFT) machinery. Here we reconstituted the first, to our knowledge, functional multi-component IFT complex that is deployed in the sensory cilia of C. elegans. Our bottom-up approach revealed the molecular basis of specific motor recruitment to the IFT trains. We identified the key component that incorporates homodimeric kinesin-2 into its physiologically relevant context, which in turn allosterically activates the motor for efficient transport. These results will enable the molecular delineation of IFT regulation, which has eluded understanding since its discovery more than two decades ago.
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Progress has been made in understanding interactions between specific IFT particle polypeptides and specific ciliary cargo proteins or motor subunits during anterograde or retrograde IFT, as well as how IFT motor activity is regulated.
“Likewise, progress has been made towards understanding the interactions between specific IFT particle polypeptides and specific ciliary cargo proteins or motor subunits during anterograde or retrograde IFT, as well as how IFT motor activity is regulated 24, 48–52.”
From Cellular signalling by primary cilia in development, organ function and disease (2019) · cites this paper as [51]
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References 33 · Cited by 38
- Authors
- Mohamed, M. A. A., Stepp, W. L., & Ökten, Z.
- Affiliations
- Technical University of Munich (DE)
- Center for Integrated Protein Science Munich (DE)
- Corresponding author
- Ökten, Zeynep
- Venue
- Nature
- Published
- 2018-05
- Volume
- 557
- Issue
- 7705
- Pages
- 387-391
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5967604
- OpenAlex
- W2802502141
- Cited by
- 38
- References
- 33
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 1 · 2022: 7 · 2021: 4 · 2020: 10 · 2019: 4 · 2018: 3
- FWCI
- 3.21
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- intraflagellar transport, kinesin-2, sensory cilia, Caenorhabditis elegans, motor unit recruitment, allosteric activation, ciliary motility
- MeSH terms
- Animals, Biological Transport, Flagella, Movement, Kinesins, Caenorhabditis elegans, Photobleaching
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