Rab11 in recycling endosomes regulates the sorting and basolateral transport of E-cadherin
Rab11 in recycling endosomes regulates the sorting and basolateral transport of E-cadherin
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DOI：
10.1091/mbc.e04-10-0867
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发表时间：
2005-04-01
影响因子：
3.3
通讯作者：
Stow, JL
中科院分区：
文献类型：
--
作者：
Lock, JG;Stow, JL
E-钙粘蛋白在细胞极性和细胞间粘附中起着重要作用;然而，E-钙粘蛋白递送至上皮细胞基底外侧膜的途径尚未完全表征。我们首先追踪了非极化细胞中GFP标记的E-cadherin（Ecad-GFP）的高尔基体后胞外转运。在活细胞中，Ecad-GFP被发现退出高尔基复合体的多形管泡载体，而不是直接移动到细胞表面，最常见的融合与一个中间室，随后确定为Rab 11阳性回收内体。在MDCK细胞中，E-钙粘蛋白的基底外侧靶向依赖于双亮氨酸基序。E-cadherin和靶向突变体Delta S1-E-cadherin与Rab 11共定位，并在分别发散到基底外侧膜或顶膜之前与回收内体融合。在极化和非极化细胞中，Rab 11突变体的共表达破坏了E-钙粘蛋白的细胞表面递送，并导致其错误定位到顶端膜，而顶端Delta S1-E-钙粘蛋白不受影响。因此，我们证明了一种新的途径Rab 11依赖，二亮氨酸介导的，亩1B-独立的排序和基底外侧贩运，以E-钙粘蛋白为例。回收内体被确定为后高尔基体运输和E-钙粘蛋白的胞吐的中间隔室，在建立和维持钙粘蛋白为基础的粘附具有潜在的重要作用。
E-cadherin plays an essential role in cell polarity and cell-cell adhesion; however, the pathway for delivery of E-cadherin to the basolateral membrane of epithelial cells has not been fully characterized. We first traced the post-Golgi, exocytic transport of GFP-tagged E-cadherin (Ecad-GFP) in unpolarized cells. In live cells, Ecad-GFP was found to exit the Golgi complex in pleiomorphic tubulovesicular carriers, which, instead of moving directly to the cell surface, most frequently fused with an intermediate compartment, subsequently identified as a Rab11-positive recycling endosome. In MDCK cells, basolateral targeting of E-cadherin relies on a dileucine motif. Both E-cadherin and a targeting mutant, Delta S1-E-cadherin, colocalized with Rab11 and fused with the recycling endosome before diverging to basolateral or apical membranes, respectively. In polarized and unpolarized cells, coexpression of Rab11 mutants disrupted the cell surface delivery of E-cadherin and caused its mistargeting to the apical membrane, whereas apical Delta S1-E-cadherin was unaffected. We thus demonstrate a novel pathway for Rab11 dependent, dileucine-mediated, mu 1B-independent sorting and basolateral trafficking, exemplified by E-cadherin. The recycling endosome is identified as an intermediate compartment for the post-Golgi trafficking and exocytosis of E-cadherin, with a potentially important role in establishing and maintaining cadherin-based adhesion.