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Figure 7


Fig. 7. Model for the effect of Mop on EGFR endocytosis in Drosophila. Upon activation of EGFR, ubiquitylation by Cbl induces EGFR internalization through clathrin-coated vesicles. These vesicles fuse with early endosomes and the EGFR is passed from the Hrs complex to the ESCRT-I, ESCRT-II and ESCRT-III complexes as the endosomes are transformed into multivesicular bodies (MVBs). ESCRT-III promotes EGFR deubiquitylation and entry into the internal vesicles of MVBs; fusion of MVBs with lysosomes results in EGFR degradation. Sprouty prevents the EGFR from progressing into late endosomes. We propose that Mop is required for EGFR progression through the endocytic pathway, perhaps through its effect on Hrs. This progression may allow EGFR to encounter crucial downstream components located on late endosomes (X), or to be recycled to the plasma membrane to prolong signaling. Cleavage of the receptor must occur at a stage after the requirement for mop.