2010年7月
Balanced ubiquitylation and deubiquitylation of Frizzled regulate cellular responsiveness to Wg/Wnt
EMBO JOURNAL
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- 巻
- 29
- 号
- 13
- 開始ページ
- 2114
- 終了ページ
- 2125
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/emboj.2010.100
- 出版者・発行元
- NATURE PUBLISHING GROUP
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. The EMBO Journal (2010) 29, 2114-2125. doi:10.1038/emboj.2010.100; Published online 21 May 2010
- リンク情報
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- DOI
- https://doi.org/10.1038/emboj.2010.100
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/20495530
- PubMed Central
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2905240
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000279630600004&DestApp=WOS_CPL
- ID情報
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- DOI : 10.1038/emboj.2010.100
- ISSN : 0261-4189
- PubMed ID : 20495530
- PubMed Central 記事ID : PMC2905240
- Web of Science ID : WOS:000279630600004