Mib1 modulates dynamin 2 recruitment via Snx18 to promote Dll1 endocytosis for efficient Notch signaling.
Mib1 modulates dynamin 2 recruitment via Snx18 to promote Dll1 endocytosis for efficient Notch signaling.
复制标题
Mib1 通过 Snx18 调节动力蛋白 2 的募集，促进 Dll1 内吞作用，从而实现有效的 Notch 信号传导。
作者：
Okano M;Matsuo H;Nishimura Y;Hozumi K;Yoshioka S;Tonoki A;Itoh M
Notch信号调节正常发育和组织稳态。配体内吞作用在Notch信号传导激活中起关键作用。内吞蛋白如胰蛋白酶和发动蛋白通过介导Notch配体内吞作用参与Notch配体活性。泛素连接酶Mib 1也通过Notch配体泛素化在Notch信号传导中发挥重要作用。然而，Mib 1和内吞蛋白之间的分子联系尚未完全确定。在这里，我们表明，Mib 1参与发动蛋白2招募Dll 1和Snx 18，与发动蛋白2相互作用，适度调节Dll 1的内吞作用。此外，Mib 1的泛素连接酶活性由Notch配体-受体相互作用诱导。Mib 1以泛素连接酶活性依赖的方式促进发动蛋白2和Snx 18之间的相互作用。这些结果表明，Mib 1通过调节Snx 18和发动蛋白2之间的相互作用来调节发动蛋白的募集，从而有助于确保Notch配体的有效信号传导活性。
Notch signaling regulates normal development and tissue homeostasis. Ligand endocytosis plays critical roles in Notch signaling activation. Endocytic proteins such as epsin and dynamin participate in Notch ligand activity by mediating Notch ligand endocytosis. The ubiquitin ligase Mib1 also plays essential roles in Notch signaling via Notch ligand ubiquitination. However, the molecular links between Mib1 and endocytic proteins have not been fully defined. Here, we show that Mib1 is involved in dynamin 2 recruitment to Dll1 and that Snx18, which interacts with dynamin 2, modestly regulates Dll1 endocytosis. Furthermore, the ubiquitin ligase activity of Mib1 is induced by Notch ligand–receptor interactions. Mib1 promotes the interaction between dynamin 2 and Snx18 in an ubiquitin ligase activity‐dependent manner. These results suggest that Mib1 modulates dynamin recruitment by regulating the interaction between Snx18 and dynamin 2, thereby helping to ensure the efficient signaling activity of Notch ligands.