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A polarized multicomponent foundation upholds ciliary central microtubules
Qingxia Chen1,2, Huijie Zhao3, Xinwen Pan4,5
1Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Institute of Early Life Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
Journal of Molecular Cell Biology
|August 21, 2024
Summary
A novel ciliary structure, the CP-foundation (CPF), supports the central pair (CP) of microtubules. Its absence causes ciliary defects and hydrocephalus in mice.
Area of Science:
- Cell Biology
- Structural Biology
- Biochemistry
Background:
- Cilia are essential for cellular function, relying on a central pair (CP) of microtubules for their coordinated beating.
- The precise mechanism maintaining the CP's position above the transition zone (TZ) is not fully understood.
Purpose of the Study:
- To elucidate the structural basis for CP stabilization within cilia.
- To identify novel components involved in CP organization and ciliary function.
Main Methods:
- Immunofluorescence microscopy to visualize CP-foundation (CPF) components.
- Proximity-dependent biotinylation (BioID) to identify CPF-associated proteins.
- Electron microscopy to assess ciliary ultrastructure.
- Phylogenetic analysis to investigate evolutionary conservation.
Main Results:
- A novel rod-like structure, the CP-foundation (CPF), composed of Cep131 and ciliary Centrin, was identified.
- The CPF assembles independently of the CP and supports its proximal end, preventing TZ penetration.
- Cep131 deficiency disrupts CPF formation, leading to CP mislocalization, ciliary abnormalities, and hydrocephalus in mice.
- Ccdc148 was identified as a CPF component, with specific localization within the structure.
Conclusions:
- The CPF is a critical, evolutionarily conserved platform that anchors the ciliary CP above the TZ.
- Dysfunction of the CPF underlies ciliary defects and associated pathologies like hydrocephalus.
- This finding reveals a new mechanism for maintaining ciliary structure and function.
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