Retromer maintains basolateral distribution of the type II TGF-β receptor via the recycling endosome.
Retromer maintains basolateral distribution of the type II TGF-β receptor via the recycling endosome.
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DOI：
10.1091/mbc.e13-02-0093
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发表时间：
2013-07
影响因子：
3.3
通讯作者：
Leof EB
中科院分区：
文献类型：
--
作者：
Yin X;Murphy SJ;Wilkes MC;Ji Y;Leof EB
在基底外侧（BL）细胞表面递送后，反转录酶促进II型TGF-β受体退出并再循环到BL质膜。然而，在没有反转录体的情况下，II型受体异常分选和定位错误，因此观察到BL和根尖的表达独立于rab11阳性的根尖循环内体。转化生长因子β (TGF-β)对上皮结构的发育和维持至关重要。由于受体的定位和转运会影响细胞和机体对TGF-β的反应，因此本研究旨在探讨这种稳态控制是如何被调节的。为此，我们确定了哺乳动物反转录复合物在维持II型TGF-β受体（t -β rii）的基底外侧质膜表达中的新作用。在TGF-β配体存在或不存在的情况下，逆转录物和t -β rii结合。逆转录物敲除后，尽管TβRII内化和转运到rab5阳性区室的情况与野生型细胞一样，受体循环受到抑制。这导致TβRII从基底外侧到基底外侧和根尖质膜的错误定位，而不依赖于高尔基转运和rab11阳性的根尖循环内体。这些数据支持一个模型，在初始基底外侧TβRII递送后，通过反转录物/TβRII结合并递送到共同循环内体，维持稳态极化的TβRII表达。
After basolateral (BL) cell surface delivery, retromer promotes type II TGF-β receptor exit and recycling to the BL plasma membrane. In the absence of retromer, however, type II receptors aberrantly sort and are mislocalized such that both BL and apical expression is observed independent of the Rab11-positive apical recycling endosome. Transforming growth factor β (TGF-β) is critical for the development and maintenance of epithelial structures. Because receptor localization and trafficking affect the cellular and organismal response to TGF-β, the present study was designed to address how such homeostatic control is regulated. To that end, we identify a new role for the mammalian retromer complex in maintaining basolateral plasma membrane expression of the type II TGF-β receptor (TβRII). Retromer and TβRII associate in the presence or absence of TGF-β ligand. After retromer knockdown, although TβRII internalization and trafficking to a Rab5-positive compartment occur as in wild-type cells, receptor recycling is inhibited. This results in TβRII mislocalization from the basolateral to both the basolateral and apical plasma membranes independent of Golgi transit and the Rab11-positive apical recycling endosome. The data support a model in which, after initial basolateral TβRII delivery, steady-state polarized TβRII expression is maintained by retromer/TβRII binding and delivery to the common recycling endosome.