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ファイル | 記述 | サイズ | フォーマット | |
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j.celrep.2018.09.045.pdf | 3.38 MB | Adobe PDF | 見る/開く |
タイトル: | A RECK-WNT7 receptor-ligand interaction enables isoform-specific regulation of Wnt bioavailability |
著者: | Vallon, Mario Yuki, Kanako Nguyen, Thi D. Chang, Junlei Yuan, Jenny Siepe, Dirk Miao, Yi Essler, Markus Noda, Makoto https://orcid.org/0000-0002-7340-6066 (unconfirmed) Garcia, K. Christopher Kuo, Calvin J. |
著者名の別形: | 野田, 亮 |
キーワード: | Wnt signaling endothelial cells central nervous system blood-brain barrier RECK WNT7 GPR124 |
発行日: | 9-Oct-2018 |
出版者: | Elsevier BV |
誌名: | Cell Reports |
巻: | 25 |
号: | 2 |
開始ページ: | 339 |
終了ページ: | 349.e9 |
抄録: | WNT7A and WNT7B control CNS angiogenesis and blood-brain barrier formation by activating endothelial Wnt/β-catenin signaling. The GPI-anchored protein RECK and adhesion G protein-coupled receptor GPR124 critically regulate WNT7-specific signaling in concert with FZD and LRP co-receptors. Here, we demonstrate that primarily the GPR124 ectodomain, but not its transmembrane and intracellular domains, mediates RECK/WNT7-induced canonical Wnt signaling. Moreover, RECK is the predominant binding partner of GPR124 in rat brain blood vessels in situ. WNT7A and WNT7B, but not WNT3A, directly bind to purified recombinant soluble RECK, full-length cell surface RECK, and the GPR124:RECK complex. Chemical cross-linking indicates that RECK and WNT7A associate with 1:1 stoichiometry, which stabilizes short-lived, active, monomeric, hydrophobic WNT7A. In contrast, free WNT7A rapidly converts into inactive, hydrophilic aggregates. Overall, RECK is a selective WNT7 receptor that mediates GPR124/FZD/LRP-dependent canonical Wnt/β-catenin signaling by stabilizing active cell surface WNT7, suggesting isoform-specific regulation of Wnt bioavailability. |
著作権等: | © 2018 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
URI: | http://hdl.handle.net/2433/234820 |
DOI(出版社版): | 10.1016/j.celrep.2018.09.045 |
PubMed ID: | 30304675 |
出現コレクション: | 学術雑誌掲載論文等 |
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