論文 - 詳細
| RRC ID | 6347 |
|---|---|
| 著者 | Dammermann A, Pemble H, Mitchell BJ, McLeod I, Yates JR 3rd, Kintner C, Desai AB, Oegema K. |
| タイトル | The hydrolethalus syndrome protein HYLS-1 links core centriole structure to cilia formation. |
| ジャーナル | Genes Dev |
| Abstract |
Centrioles are subcellular organelles composed of a ninefold symmetric microtubule array that perform two important functions: (1) They build centrosomes that organize the microtubule cytoskeleton, and (2) they template cilia, microtubule-based projections with sensory and motile functions. We identified HYLS-1, a widely conserved protein, based on its direct interaction with the core centriolar protein SAS-4. HYLS-1 localization to centrioles requires SAS-4 and, like SAS-4, HYLS-1 is stably incorporated into the outer centriole wall. Unlike SAS-4, HYLS-1 is dispensable for centriole assembly and centrosome function in cell division. Instead, HYLS-1 plays an essential role in cilia formation that is conserved between Caenorhabditis elegans and vertebrates. A single amino acid change in human HYLS1 leads to a perinatal lethal disorder termed hydrolethalus syndrome, and we show that this mutation impairs HYLS-1 function in ciliogenesis. HYLS-1 is required for the apical targeting/anchoring of centrioles at the plasma membrane but not for the intraflagellar transport-dependent extension of the ciliary axoneme. These findings classify hydrolethalus syndrome as a severe human ciliopathy and shed light on the dual functionality of centrioles, defining the first stably incorporated centriolar protein that is not required for centriole assembly but instead confers on centrioles the capacity to initiate ciliogenesis. |
| 巻・号 | 23(17) |
| ページ | 2046-59 |
| 公開日 | 2009-9-1 |
| DOI | 10.1101/gad.1810409 |
| PII | gad.1810409 |
| PMID | 19656802 |
| PMC | PMC2751977 |
| MeSH | Amino Acid Sequence Animals Behavior, Animal / physiology Caenorhabditis elegans / cytology* Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Division Centrioles / metabolism* Cilia / physiology* Embryo, Nonmammalian / cytology Embryo, Nonmammalian / physiology Humans Molecular Sequence Data Mutation / genetics Neurons / metabolism Protein Transport Sequence Alignment Transcription Factors / metabolism Xenopus laevis / genetics Xenopus laevis / metabolism |
| IF | 9.527 |
| 引用数 | 41 |
| WOS 分野 | GENETICS & HEREDITY DEVELOPMENTAL BIOLOGY CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | F1000Research |
| 各媒体での言及数の合計 | 6 |
| 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 | tm3067 |