Figure 7.

Proposed itinerary of TGF-β receptors in Dab2 WT and Dab2 KD cells. 1) TGF-β receptors internalize via clathrin-coated pits where AP2, Dab2, and other adaptors may be present. Dab2 is not required for initial endocytosis. 2) In the absence of ligand, receptors travel to an EEA1-positive early endosome compartment (EE) and travel back to the cell surface via a Rab11-positive recycling endosome (RE) (3). Because Dab2 binds the receptors constitutively (Hocevar et al., 2001), it is currently unknown whether it accompanies the receptor complex to the early endosome, or alternatively, dissociates after internalization. Dab2 or an unidentified associated adaptor protein recruited by Dab2, may assist in translocation of receptors to the Rab11-positive recycling compartment (3). In the absence of Dab2 and/or Dab2-associated proteins, endocytosed receptors (4) are sequestered in a perinuclear EEA1 associated compartment (5), some of which become enlarged early endosomes (EEE). Although the type I receptor was not directly assessed, our previous work has established that both type I and type II receptors display similar trafficking behavior (Mitchell et al., 2004).