Ce. Futter et al., MULTIVESICULAR ENDOSOMES CONTAINING INTERNALIZED EGF-EGF RECEPTOR COMPLEXES MATURE AND THEN FUSE DIRECTLY WITH LYSOSOMES, The Journal of cell biology, 132(6), 1996, pp. 1011-1023
We have followed the transfer of EGF-EGF receptor (EGFR) complexes fro
m endosomal vacuoles that contain transferrin receptors (TfR) to lysos
ome vacuoles identified by their content of HRP loaded as a 15-min pul
se 4 h previously. We show that the HRP-loaded lysosomes are lysosomal
-associated membrane protein-1 (LAMP-1) positive, mannose-6-phosphate
receptor (M6PR) negative, and contain active acid hydrolase. EGF-EGFR
complexes are delivered to these lysosomes intact and are then rapidly
degraded. Preactivating the HRP contained within the preloaded lysoso
mes inhibits the delivery of EGFR and degradation of EGF, and results
in the accumulation of EGFR-containing multivesicular bodies (MVB). Wi
th time these accumulating MVB undergo a series of maturation changes
that include the loss of TfR, the continued recruitment of EGFR, and t
he accumulation of internal vesicles, but they remain LAMP-1 and M6PR
negative, The mature MVB are often seen to make direct contact with ly
sosomes containing preactivated HRP, but their perimeter membranes rem
ain intact. Together our observations suggest that the transfer of EGF
-EGFR complexes from the TfR-containing endosome compartment to the ly
sosomes that degrade them employs a single vacuolar intermediate, the
maturing MVB, and can be achieved by a single heterotypic fusion step.