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PreprintCited by 48Genetic and Kidney Cyst DiseasesCystic Fibrosis Research AdvancesAdvanced Electron Microscopy Techniques and Applications

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Structural organization of the C1a-e-c supercomplex within the ciliary central apparatus

Open access
Fu, Gang, Zhao, Lei, Dymek, Erin, Hou, Yuqing, Song, Kangkang, Phan, Nhan, Shang, Zhiguo, Smith, Elizabeth F., Witman, George B., Nicastro, Daniela·2019·The Journal of Cell Biology
DOI 10.1101/773416PMC PMC6891083

Preprint — published as 10.1083/jcb.201906006 · Paper page

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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 MDa) 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 three-dimensional (3D) structure of the CA, which is a prerequisite for understanding the molecular mechanisms by which the CA regulates ciliary beating. Summary: Fu et al. use a wild-type vs. mutant comparison and cryo-electron tomography of Chlamydomonas flagella to identify central apparatus (CA) subunits and visualize their location in the native 3D CA structure. The study provides a better understanding of the CA and how it regulates ciliary motility.

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Metadata

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
The Journal of Cell Biology
Publisher
openRxiv
Published
2019-09-18
Volume
218
Issue
12
Pages
4236-4251
ISSN
0021-9525 (ISSN-L)
DOI
10.1101/773416
PMC
PMC6891083
OpenAlex
W2989414036
Cited by
48
References
1
Citations by year
2026: 4 · 2025: 5 · 2024: 4 · 2023: 12 · 2022: 6 · 2021: 7 · 2020: 5 · 2019: 3
FWCI
3.15
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
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)
  • University of Texas Southwestern Medical Center
  • Dartmouth College
  • National Institutes of Health (RP170644)
  • National Institute of General Medical Sciences (R35GM122574, R01GM083122, R01GM112050)
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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