1. Retromer maintains basolateral distribution of the type II TGF-β receptor via the recycling endosome
- Author
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Yan Ji, Edward B. Leof, Xueqian Yin, Mark C. Wilkes, and Stephen J. Murphy
- Subjects
Receptor recycling ,Retromer ,Endosome ,Vesicular Transport Proteins ,Endosomes ,Protein Serine-Threonine Kinases ,Biology ,Madin Darby Canine Kidney Cells ,symbols.namesake ,Dogs ,Transforming Growth Factor beta ,Cell polarity ,Animals ,Humans ,Molecular Biology ,rab5 GTP-Binding Proteins ,Cell Membrane ,Receptor, Transforming Growth Factor-beta Type II ,Cell Polarity ,Articles ,Cell Biology ,Basolateral plasma membrane ,Golgi apparatus ,Apical recycling endosome ,Cell biology ,Retromer complex ,Protein Transport ,Gene Expression Regulation ,Membrane Trafficking ,rab GTP-Binding Proteins ,symbols ,Receptors, Transforming Growth Factor beta ,Signal Transduction - Abstract
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.
- Published
- 2013