論文 - 詳細
| RRC ID | 11084 |
|---|---|
| 著者 | Mukai A, Yamamoto-Hino M, Awano W, Watanabe W, Komada M, Goto S. |
| タイトル | Balanced ubiquitylation and deubiquitylation of Frizzled regulate cellular responsiveness to Wg/Wnt. |
| ジャーナル | EMBO J |
| Abstract |
Wingless (Wg)/Wnt has been proposed to exert various functions as a morphogen depending on the levels of its signalling. Therefore, not just the concentration of Wg/Wnt, but also the responsiveness of Wg/Wnt-target cells to the ligand, must have a crucial function in controlling cellular outputs. Here, we show that a balance of ubiquitylation and deubiquitylation of the Wg/Wnt receptor Frizzled determines the cellular responsiveness to Wg/Wnt both in mammalian cells and in Drosophila, and that the cell surface level of Frizzled is regulated by deubiquitylating enzyme UBPY/ubiquitin-specific protease 8 (USP8). Although ubiquitylated Frizzled underwent lysosomal trafficking and degradation, UBPY/USP8-dependent deubiquitylation led to recycling of Frizzled to the plasma membrane, thereby elevating its surface level. Importantly, a gain and loss of UBPY/USP8 function led to up- and down-regulation, respectively, of canonical Wg/Wnt signalling. These results unveil a novel mechanism that regulates the cellular responsiveness to Wg/Wnt by controlling the cell surface level of Frizzled. |
| 巻・号 | 29(13) |
| ページ | 2114-25 |
| 公開日 | 2010-7-7 |
| DOI | 10.1038/emboj.2010.100 |
| PII | emboj2010100 |
| PMID | 20495530 |
| PMC | PMC2905240 |
| MeSH | Animals Cell Line Drosophila / embryology* Drosophila / metabolism* Drosophila Proteins / metabolism* Endocytosis Frizzled Receptors / metabolism* Gene Expression Regulation Humans Larva / metabolism Protein Transport Ubiquitin Thiolesterase / genetics Ubiquitin Thiolesterase / metabolism Ubiquitin-Specific Proteases / metabolism* Ubiquitination* Wings, Animal / embryology Wings, Animal / metabolism Wnt Proteins / metabolism Wnt1 Protein / metabolism* |
| IF | 9.889 |
| 引用数 | 95 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
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オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 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 |
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