EGF induces macropinocytosis and SNX1-modulated recycling of E-cadherin
EGF induces macropinocytosis and SNX1-modulated recycling of E-cadherin
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DOI：
10.1242/jcs.000653
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发表时间：
2007-05-15
影响因子：
4
通讯作者：
Stow, Jennifer L.
中科院分区：
文献类型：
--
作者：
Bryant, David M.;Kerr, Markus C.;Stow, Jennifer L.
在上皮细胞中，连接蛋白被内吞以调节细胞-细胞粘附和细胞极性。在响应于生长因子，细胞-细胞粘附蛋白E-钙粘蛋白从细胞表面内化，降解或再循环作为潜在的命运。然而，参与钙粘蛋白内化和再循环的细胞机制仍然存在争议。在这里，我们研究了EGF诱导的E-钙粘蛋白内化。EGF刺激MCF-7细胞导致Rac 1调节的E-钙粘蛋白-连环蛋白复合物巨胞饮进入与EEA 1和分选连接蛋白SNX 1共定位的内体隔室。通过siRNA消耗细胞SNX 1水平导致细胞内积累增加，并且响应EGF从细胞表面内化的E-cadherin的周转增加。此外，SNX 1也需要有效回收内化的E-钙粘蛋白和重建上皮粘附。总之，这些研究结果表明SNX 1在从降解内体途径中检索E-钙粘蛋白和调节E-钙粘蛋白再循环的膜运输途径中的作用。
In epithelia, junction proteins are endocytosed for modulation of cell-cell adhesion and cell polarity. In response to growth factors, the cell-cell adhesion protein E-cadherin is internalized from the cell surface with degradation or recycling as potential fates. However, the cellular machinery involved in cadherin internalization and recycling remains controversial. Here we investigated EGF-induced E-cadherin internalization. EGF stimulation of MCF-7 cells resulted in Rac1-modulated macropinocytosis of the E-cadherin-catenin-complex into endosomal compartments that colocalized with EEA1 and the sorting nexin, SNX1. Depletion of cellular SNX1 levels by siRNA resulted in increased intracellular accumulation and turnover of E-cadherin internalized from the cell surface in response to EGF. Moreover, SNX1 was also required for efficient recycling of internalized E-cadherin and re-establishment of epithelial adhesion. Together, these findings demonstrate a role for SNX1 in retrieval of E-cadherin from a degradative endosomal pathway and in membrane trafficking pathways that regulate E-cadherin recycling.