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Published on: December 20, 2014
Distinct roles of centriole distal appendage proteins in ciliary assembly and disassembly
Su-Yeon Je1,2, Hyuk Wan Ko3,4,5
1Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea.
Insights
Distal appendage proteins regulate primary cilium assembly and disassembly. Two subgroups were identified: one for assembly (CEP83, SCLT1, CEP164) and another for disassembly (CEP89, FBF1), impacting cell cycle signaling.
Area of Science:
- Cell Biology
- Molecular Biology
Background:
- The primary cilium is a crucial organelle involved in cell signaling and development.
- The centriole distal appendage (DA) is vital for initiating ciliogenesis by anchoring the mother centriole.
- The specific roles of DA proteins in ciliary dynamics remain largely unknown.
Purpose of the Study:
- To elucidate the precise functions of distal appendage proteins in primary cilium assembly and disassembly.
- To functionally categorize distal appendage proteins based on their roles in ciliary dynamics.
Main Methods:
- Utilized siRNA-mediated knockdown to assess the function of distal appendage proteins.
- Analyzed ciliary assembly and disassembly kinetics in mutant and knockdown cells.
- Investigated the impact on the Aurora A kinase signaling pathway.
Main Results:
- Cep89 mutant cells showed normal ciliogenesis but delayed ciliary disassembly.
- DA proteins were functionally divided into two groups: CEP83, SCLT1, and CEP164 for assembly/docking, and CEP89 and FBF1 for disassembly.
- CEP89 and FBF1 depletion impaired disassembly and disrupted Aurora A kinase localization and signaling.
Conclusions:
- Distal appendage proteins form functional modules for distinct aspects of ciliary dynamics.
- CEP89 and FBF1 play a specific role in regulating ciliary disassembly and Aurora A kinase signaling.
- These findings have implications for understanding cellular signaling, homeostasis, and development.
Abstract:
The primary cilium is a cellular organelle whose assembly and disassembly are closely linked to the cell cycle. The centriole distal appendage (DA) is essential for the early stages of ciliogenesis by anchoring the mother centriole to the cell surface. Despite the identification of over twelve proteins constituting the DA, including CEP83, CEP89, CEP164, FBF1, and SCLT1, their specific functions in ciliary dynamics are not fully understood. Here, we elucidate the precise role of DA proteins in ciliary assembly and disassembly. While Cep89 mutant cells exhibit normal ciliogenesis, the kinetics of ciliary disassembly is significantly delayed. Through siRNA-mediated knockdown of DA proteins, we identified two functional subgroups within DA proteins: CEP83, SCLT1, and CEP164, which are primarily essential for ciliary assembly and centriole docking, and CEP89 and FBF1, which specifically regulate ciliary disassembly. Notably, the depletion of CEP89 and FBF1 not only impedes ciliary disassembly but also disrupts the Aurora A kinase signaling pathway, leading to its downregulation and mislocalization at the basal body during serum-induced cell cycle re-entry. These findings suggest that DA components can be functionally categorized into two modules responsible for distinct aspects of ciliary dynamics, with broad implications for cellular signaling, homeostasis, and development.
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