Structural organization of the C1a-e-c supercomplex within the ciliary central apparatus
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Abstract
Nearly all motile cilia contain a central apparatus (CA) composed of two connected singlet microtubules with attached projections that play crucial roles in regulating ciliary motility. Defects in CA assembly usually result in motility-impaired or paralyzed cilia, which in humans causes disease. Despite their importance, the protein composition and functions of the CA projections are largely unknown. Here, we integrated biochemical and genetic approaches with cryo-electron tomography to compare the CA of wild-type Chlamydomonas with CA mutants. We identified a large (>2 MD) complex, the C1a-e-c supercomplex, that requires the PF16 protein for assembly and contains the CA components FAP76, FAP81, FAP92, and FAP216. We localized these subunits within the supercomplex using nanogold labeling and show that loss of any one of them results in impaired ciliary motility. These data provide insight into the subunit organization and 3D structure of the CA, which is a prerequisite for understanding the molecular mechanisms by which the CA regulates ciliary beating.
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Cites
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Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., & Selbach, M. (2011) · Nature · doi:10.1038/nature10098 · Cited by 6,566 · cited 2× · see citing works
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MethodAbsolute Quantification of Proteins by LCMSE
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TIM, a targeted insertional mutagenesis method utilizing CRISPR/Cas9 in Chlamydomonas reinhardtii
Picariello, T., Hou, Y., Kubo, T., McNeill, N. A., Yanagisawa, H.-A., Oda, T., & Witman, G. B. (2020) · PLOS ONE · doi:10.1371/journal.pone.0232594 · Cited by 83 · see citing works
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- Authors
- Fu, G., Zhao, L., Dymek, E., Hou, Y., Song, K., Phan, N., Shang, Z., Smith, E. F., Witman, G. B., & Nicastro, D.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- University of Massachusetts Chan Medical School (US)
- Dartmouth College (US)
- Corresponding author
- Nicastro, Daniela
- ORCID
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2019-10-31
- Volume
- 218
- Issue
- 12
- Pages
- 4236-4251
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC6891083
- OpenAlex
- W2989414036
- Cited by
- 48
- References
- 2
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 4 · 2023: 12 · 2022: 6 · 2021: 7 · 2020: 5 · 2019: 3 · 2018: 2
- FWCI
- 3.15
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion, cc-by-nc-sa)
- Funders
- Cancer Prevention and Research Institute of Texas (RP170644, RR140082)
- National Institutes of Health (R01 GM083122, R35 GM122574, R01 GM112050)
- 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 › Structural Biology › Advanced Electron Microscopy Techniques and Applications
- Keywords
- Chlamydomonas, ciliary motility, supercomplex assembly, cryo-electron tomography, motility defects
- MeSH terms
- Cell Movement, Chlamydomonas, Cilia, Flagella, Genotype, Microtubules, Molecular Conformation, Mutation, Phenotype, Polymerase Chain Reaction, Axoneme, Electron Microscope Tomography
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