We have followed the transfer of EGF-EGF receptor (EGFR) complexes from endosomal vacuoles that contain transferrin receptors (TfR) to lysosome vacuoles identified by their content of HRP loaded as a 15-min pulse 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 lysosomes inhibits the delivery of EGFR and degradation of EGF, and results in the accumulation of EGFR-containing multivesicular bodies (MVB). With time these accumulating MVB undergo a series of maturation changes that include the loss of TfR, the continued recruitment of EGFR, and the accumulation of internal vesicles, but they remain LAMP-1 and M6PR negative. The mature MVB are often seen to make direct contact with lysosomes containing preactivated HRP, but their perimeter membranes remain intact. Together our observations suggest that the transfer of EGF-EGFR complexes from the TfR-containing endosome compartment to the lysosomes that degrade them employs a single vacuolar intermediate, the maturing MVB, and can be achieved by a single heterotypic fusion step.
Article|
March 15 1996
Multivesicular endosomes containing internalized EGF-EGF receptor complexes mature and then fuse directly with lysosomes.
C E Futter,
C E Futter
Medical Research Council Laboratory for Molecular Cell Biology, University College, London, United Kingdom.
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A Pearse,
A Pearse
Medical Research Council Laboratory for Molecular Cell Biology, University College, London, United Kingdom.
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L J Hewlett,
L J Hewlett
Medical Research Council Laboratory for Molecular Cell Biology, University College, London, United Kingdom.
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C R Hopkins
C R Hopkins
Medical Research Council Laboratory for Molecular Cell Biology, University College, London, United Kingdom.
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C E Futter
Medical Research Council Laboratory for Molecular Cell Biology, University College, London, United Kingdom.
A Pearse
Medical Research Council Laboratory for Molecular Cell Biology, University College, London, United Kingdom.
L J Hewlett
Medical Research Council Laboratory for Molecular Cell Biology, University College, London, United Kingdom.
C R Hopkins
Medical Research Council Laboratory for Molecular Cell Biology, University College, London, United Kingdom.
Online ISSN: 1540-8140
Print ISSN: 0021-9525
J Cell Biol (1996) 132 (6): 1011–1023.
Citation
C E Futter, A Pearse, L J Hewlett, C R Hopkins; Multivesicular endosomes containing internalized EGF-EGF receptor complexes mature and then fuse directly with lysosomes.. J Cell Biol 15 March 1996; 132 (6): 1011–1023. doi: https://doi.org/10.1083/jcb.132.6.1011
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