論文 - 詳細
| RRC ID | 71754 |
|---|---|
| 著者 | Ishida Y, Tasaki K, Katoh Y, Nakayama K. |
| タイトル | Molecular basis underlying the ciliary defects caused by IFT52 variations found in skeletal ciliopathies. |
| ジャーナル | Mol Biol Cell |
| Abstract |
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. |
| 巻・号 | 33(9) |
| ページ | ar83 |
| 公開日 | 2022-8-1 |
| DOI | 10.1091/mbc.E22-05-0188 |
| PMID | 35704471 |
| PMC | PMC9582644 |
| MeSH | Adaptor Proteins, Signal Transducing / metabolism Cilia / metabolism Ciliopathies* / genetics Ciliopathies* / metabolism Cytoskeletal Proteins / metabolism Dyneins* / metabolism Flagella / metabolism Humans Mutation / genetics Protein Transport |
| IF | 3.791 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | 293T(RCB2202) |