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タイトル: | Molecular basis underlying the ciliary defects caused by IFT52 variations found in skeletal ciliopathies |
著者: | Ishida, Yamato Tasaki, Koshi Katoh, Yohei https://orcid.org/0000-0003-1649-4917 (unconfirmed) Nakayama, Kazuhisa https://orcid.org/0000-0001-7701-7183 (unconfirmed) |
著者名の別形: | 石田, 大和 田崎, 晃司 加藤, 洋平 中山, 和久 |
発行日: | 1-Aug-2022 |
出版者: | American Society for Cell Biology (ASCB) |
誌名: | Molecular Biology of the Cell |
巻: | 33 |
号: | 9 |
論文番号: | ar83 |
抄録: | Bidirectional protein trafficking within cilia is mediated by the intraflagellar transport (IFT) machinery, which contains the IFT-A and IFT-B complexes powered by the kinesin-2 and dynein-2 motors. Mutations in genes encoding subunits of the IFT-A and dynein-2 complexes cause skeletal ciliopathies. Some subunits of the IFT-B complex, including IFT52, IFT80, and IFT172, are also mutated in skeletal ciliopathies. We here show that IFT52 variants found in individuals with short-rib polydactyly syndrome (SRPS) are compromised in terms of formation of the IFT-B holocomplex from two subcomplexes, and its interaction with heterotrimeric kinesin-II. IFT52-knockout (KO) cells expressing IFT52 variants that mimic the cellular conditions of individuals with SRPS demonstrated mild ciliogenesis defects and a decrease in ciliary IFT-B level. Furthermore, in IFT52-KO cells expressing an SRPS variant of IFT52, ciliary tip localization of ICK/CILK1 and KIF17, both of which are likely to be transported to the tip via binding to the IFT-B complex, were significantly impaired. These results altogether indicate that impaired anterograde trafficking caused by a decrease in the ciliary level of IFT-B or in its binding to kinesin-II underlies the ciliary defects found in skeletal ciliopathies caused by IFT52 variations. |
著作権等: | © 2022 Ishida et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial-Share Alike 4.0 International Creative Commons License |
URI: | http://hdl.handle.net/2433/276723 |
DOI(出版社版): | 10.1091/mbc.E22-05-0188 |
PubMed ID: | 35704471 |
出現コレクション: | 学術雑誌掲載論文等 |
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