Retromer maintains basolateral distribution of the type II TGF-β receptor via the recycling endosome

Transforming growth factor beta (TGF-beta) is critical for the development and maintenance of epithelial structures. Because receptor localization and trafficking affect the cellular and organismal response to TGF-beta, 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-beta receptor (T beta RII). Retromer and T beta RII associate in the presence or absence of TGF-beta ligand. After retromer knockdown, although T beta RII internalization and trafficking to a Rab5-positive compartment occur as in wild-type cells, receptor recycling is inhibited. This results in T beta RII 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 T beta RII delivery, steady-state polarized T beta RII expression is maintained by retromer/T beta RII binding and delivery to the common recycling endosome.