論文 - 詳細
| RRC ID | 45588 |
|---|---|
| 著者 | Lambacher NJ, Bruel AL, van Dam TJ, Szymańska K, Slaats GG, Kuhns S, McManus GJ, Kennedy JE, Gaff K, Wu KM, van der Lee R, Burglen L, Doummar D, Rivière JB, Faivre L, Attié-Bitach T, Saunier S, Curd A, Peckham M, Giles RH, Johnson CA, Huynen MA, Thauvin-Robinet C, Blacque OE. |
| タイトル | TMEM107 recruits ciliopathy proteins to subdomains of the ciliary transition zone and causes Joubert syndrome. |
| ジャーナル | Nat Cell Biol |
| Abstract |
The transition zone (TZ) ciliary subcompartment is thought to control cilium composition and signalling by facilitating a protein diffusion barrier at the ciliary base. TZ defects cause ciliopathies such as Meckel-Gruber syndrome (MKS), nephronophthisis (NPHP) and Joubert syndrome (JBTS). However, the molecular composition and mechanisms underpinning TZ organization and barrier regulation are poorly understood. To uncover candidate TZ genes, we employed bioinformatics (coexpression and co-evolution) and identified TMEM107 as a TZ protein mutated in oral-facial-digital syndrome and JBTS patients. Mechanistic studies in Caenorhabditis elegans showed that TMEM-107 controls ciliary composition and functions redundantly with NPHP-4 to regulate cilium integrity, TZ docking and assembly of membrane to microtubule Y-link connectors. Furthermore, nematode TMEM-107 occupies an intermediate layer of the TZ-localized MKS module by organizing recruitment of the ciliopathy proteins MKS-1, TMEM-231 (JBTS20) and JBTS-14 (TMEM237). Finally, MKS module membrane proteins are immobile and super-resolution microscopy in worms and mammalian cells reveals periodic localizations within the TZ. This work expands the MKS module of ciliopathy-causing TZ proteins associated with diffusion barrier formation and provides insight into TZ subdomain architecture. |
| 巻・号 | 18(1) |
| ページ | 122-31 |
| 公開日 | 2016-1-1 |
| DOI | 10.1038/ncb3273 |
| PII | ncb3273 |
| PMID | 26595381 |
| PMC | PMC5580800 |
| MeSH | Abnormalities, Multiple / genetics Abnormalities, Multiple / metabolism Animals Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / metabolism Cerebellum / abnormalities* Cerebellum / metabolism Cilia / metabolism* Eye Abnormalities / genetics Eye Abnormalities / metabolism Humans Kidney Diseases, Cystic / genetics Kidney Diseases, Cystic / metabolism Membrane Proteins / genetics Membrane Proteins / metabolism* Retina / abnormalities* Retina / metabolism |
| IF | 20.042 |
| 引用数 | 49 |
| WOS 分野 | CELL BIOLOGY |
| 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 | 20 |
| 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 | |
| 線虫 | tm925 tm3083 |