FIGURE 2.
Model showing involvement of various proteins in CFTR endocytosis and recycling
CFTR (brown rectangle) is endocytosed from the apical plasma membrane in a clathrin-dependent process that requires dynamin (for vesicle fission), the μ subunit of the AP-2 adaptor complex that mediates interaction between the YDSI endocytic motif on CFTR and the clathrin lattice. The endocytosis of CFTR also requires myosin-VI, a molecular motor that drives cargo to the minus end of F-actin (i.e., inwardly directed). Several members of the RabGTPase family have been shown to modulate CFTR trafficking. Rab5 promotes endocytosis of CFTR. Exit of CFTR from early endosomes can be mediated by Rab4 which directly targets CFTR back to the plasma membrane, or by Rab7 which increases CFTR degradation by enhancing the trafficking of CFTR to late endosomes and lysosomes. Rab9 mediates CFTR trafficking from late endosomes to the trans Golgi network (TGN). Rab11 mediates CFTR trafficking from recycling endosomes to either the plasma membrane or to the TGN. RME-1 facilitates exit of CFTR from the recycling endosome. PDZ binding proteins can inhibit CFTR endocytosis from the plasma membrane, as well as facilitate recycling of internalized CFTR from early endosomes.