Ligand-dependent and -independent transforming growth factor-beta receptor recycling regulated by clathrin-mediated endocytosis and Rab11

Proteins in the transforming growth factor-beta (TGF-beta) family recognize transmembrane serine/threonine kinases known as type I and type II receptors. Binding of TGF-beta to receptors results in receptor down-regulation and signaling. Whereas previous work has focused on activities controlling TGF-beta signaling, more recent studies have begun to address the trafficking properties of TGF-beta receptors. In this report, it is shown that receptors undergo recycling both in the presence and absence of ligand activation, with the rates of internalization and recycling being unaffected by ligand binding. Recycling occurs as receptors are most likely internalized through clathrin-coated pits, and then returned to the plasma membrane via a rab11-dependent, rab4-independent mechanism. Together, the results suggest a mechanism wherein activated TGF-beta receptors are directed to a distinct endocytic pathway for down-regulation and clathrin-dependent degradation after one or more rounds of recycling.