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.