Sorting nexin 17 prevents lysosomal degradation of β1 integrins by binding to the β1-integrin tail
Sorting nexin 17 prevents lysosomal degradation of β1 integrins by binding to the β1-integrin tail
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DOI：
10.1038/ncb2501
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发表时间：
2012-06-01
影响因子：
21.3
通讯作者：
Faessler, Reinhard
中科院分区：
文献类型：
--
作者：
Boettcher, Ralph Thomas;Stremmel, Christopher;Faessler, Reinhard
整联蛋白的功能是通过调节其对配体的亲和力以及通过完整整联蛋白通过内体的有效再循环来控制的。在这里，我们证明β（1）-整联蛋白胞质结构域中的Kindlin结合位点充当分子开关，使不同细胞区室中两种含有FERM结构域的蛋白质能够顺序结合。当β（1）整联蛋白位于质膜时，Kindlin控制配体结合亲和力。然而，当它们被内化时，Kindlin与整联蛋白解离，并且分选连接蛋白17（SNX 17）被募集以在早期内体中释放β（1）-整联蛋白尾部，以防止β（1）-整联蛋白降解，导致它们再循环回到细胞表面。我们的研究结果将SNX 17鉴定为β（1）-整联蛋白尾部结合蛋白，其与内体中的游离Kindlin结合位点相互作用以稳定β（1）整联蛋白，导致其再循环至细胞表面，在那里它们可以被重复使用。
Integrin functions are controlled by regulating their affinity for ligand, and by the efficient recycling of intact integrins through endosomes. Here we demonstrate that the Kindlin-binding site in the beta(1)-integrin cytoplasmic domain serves as a molecular switch enabling the sequential binding of two FERM-domain-containing proteins in different cellular compartments. When beta(1) integrins are at the plasma membrane, Kindlins control ligand-binding affinity. However, when they are internalized, Kindlins dissociate from integrins and sorting nexin 17 (SNX17) is recruited to free beta(1)-integrin tails in early endosomes to prevent beta(1)-integrin degradation, leading to their recycling back to the cell surface. Our results identify SNX17 as a beta(1)-integrin-tail-binding protein that interacts with the free Kindlin-binding site in endosomes to stabilize beta(1) integrins, resulting in their recycling to the cell surface where they can be reused.