Schematic of Rab5 mediated endosomal trafficking in receptor down-regulation and influences by free p85.
Cartoon summarising endosomal trafficking and the known points of influence of free p85. The ligand-bound receptor is internalised within an intracellular clathrin lattice. The clathrin lattice invaginates forming a clathrin-coated pit that pinches off to form a clathrin-coated vesicle. This intermediate vesicle fuses with the early endosome, delivering the receptor. This vesicle fusion event is mediated by Rab5 that localises to early endosomes. p85 GAP activity towards Rab5·GTP switches off this initial fusion event and is implicated in receptor down-regulation. The RTK-containing early endosome can also be trafficked through the endocytic pathway to the lysosome for degradation. AP2, adaptor protein2; GF, growth factor; SNX9, sorting nexin 9; GAP, GTPase activating protein; GEF, guanine nucleotide exchange factor.