Persistent cell migration and adhesion rely on retrograde transport of β1 integrin
Persistent cell migration and adhesion rely on retrograde transport of β1 integrin
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DOI：
10.1038/ncb3287
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发表时间：
2016-01-01
影响因子：
21.3
通讯作者：
Johannes, Ludger
中科院分区：
文献类型：
--
作者：
Shafaq-Zadah, Massiullah;Gomes-Santos, Carina S.;Johannes, Ludger
整合素在细胞粘附和迁移中具有关键功能。整合素是如何动态地重新定位到高度极化的迁移细胞的前沿仍然没有探索。在这里，我们证明了β（1）整合素（在秀丽隐杆线虫中称为PAT-3），而不是β（3），从质膜转运到trans-Golgi网络，以极化方式重新分泌。这种逆向运输仅限于β（1）整联蛋白的非配体结合构象。逆行运输抑制消除了几种β（1）-整合素特异性功能，如小鼠早期胚胎发育中的细胞粘附，以及C.优雅我们的研究结果建立了一个范式，根据该范式，逆行运输，而不是内体再循环，是高度极化细胞中β（1）整合素功能的关键驱动因素。这些数据更普遍地表明，逆行路线是用来重新定位质膜机器从以前的网站的功能迁移细胞的前缘。
Integrins have key functions in cell adhesion and migration. How integrins are dynamically relocalized to the leading edge in highly polarized migratory cells has remained unexplored. Here, we demonstrate that beta(1) integrin (known as PAT-3 in Caenorhabditis elegans), but not beta(3), is transported from the plasma membrane to the trans-Golgi network, to be resecreted in a polarized manner. This retrograde trafficking is restricted to the non-ligand-bound conformation of beta(1) integrin. Retrograde trafficking inhibition abrogates several beta(1)-integrin-specific functions such as cell adhesion in early embryonic development of mice, and persistent cell migration in the developing posterior gonad arm of C. elegans. Our results establish a paradigm according to which retrograde trafficking, and not endosomal recycling, is the key driver for beta(1) integrin function in highly polarized cells. These data more generally suggest that the retrograde route is used to relocalize plasma membrane machinery from previous sites of function to the leading edge of migratory cells.