Abstract
Motile cilia can beat with distinct patterns, but how motility variations are regulated remain obscure. Here, we have studied the role of the coiled-coil protein CFAP53 in the motility of different cilia-types in the mouse. While node (9+0) cilia of Cfap53 mutants were immotile, tracheal and ependymal (9+2) cilia retained motility, albeit with an altered beat pattern. In node cilia, CFAP53 mainly localized at the base (centriolar satellites), whereas it was also present along the entire axoneme in tracheal cilia. CFAP53 associated tightly with microtubules and interacted with axonemal dyneins and TTC25, a dynein docking complex component. TTC25 and outer dynein arms (ODAs) were lost from node cilia, but were largely maintained in tracheal cilia of Cfap53-/- mice. Thus, CFAP53 at the base of node cilia facilitates axonemal transport of TTC25 and dyneins, while axonemal CFAP53 in 9+2 cilia stabilizes dynein binding to microtubules. Our study establishes how differential localization and function of CFAP53 contributes to the unique motion patterns of two important mammalian cilia-types.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Axonemal Dyneins / genetics
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Axonemal Dyneins / metabolism*
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Axoneme / genetics
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Axoneme / metabolism*
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Biological Transport, Active / genetics*
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Cell Movement / genetics*
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Cilia / genetics
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Cilia / metabolism*
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Embryo, Mammalian / metabolism*
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Embryo, Mammalian / physiology
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Embryo, Mammalian / ultrastructure
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Ependyma / embryology
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Ependyma / metabolism
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Ependyma / physiology
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Fluorescent Antibody Technique
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Genotype
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Immunoprecipitation
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Mice
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Mice, Knockout
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Microscopy, Electron, Transmission
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Microtubules / genetics
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Microtubules / metabolism*
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Mutation
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Phenotype
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Trachea / embryology
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Trachea / metabolism
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Trachea / physiology
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Trachea / ultrastructure
Substances
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Carrier Proteins
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TTC25 protein, mouse
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Axonemal Dyneins
Grants and funding
This work was supported by funds from the Agency for Science, Technology and Research (A*STAR) of Singapore (Grant No. SC15-R0010,
https://www.a-star.edu.sg/) to S.R. and grants from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan (Grant No.17H01435,
https://www.mext.go.jp/en/index.htm) to H.H.,(Grant No. 17K15123) to T.I. and from Core Research for Evolutional Science and Technology (CREST) of the Japan Science and Technology Agency (Grant No. JPMJCR13W5,
https://www.jst.go.jp/kisoken/crest/en/index.html) to H.H., grants from Japan Society for Promotion of Science (Grant No. 17H05895,
https://www.jsps.go.jp/english/e-grants/index.html) to T.I. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.