The delivery of endocytosed cargo to lysosomes occurs through kissing and direct fusion of late endosomes/MVBs (multivesicular bodies) and lysosomes. Live-cell and electron microscopy experiments together with cell-free assays have allowed us to describe the characteristics of the delivery process and determine the core protein machinery required for fusion. The ESCRT (endosomal sorting complex required for transport) machinery is required for MVB biogenesis. The HOPS (homotypic fusion and vacuole protein sorting) complex is required for endosome–lysosome tethering and a trans-SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein receptor) complex including the R-SNARE VAMP7 (vesicle-associated membrane protein 7) mediates endosome–lysosome membrane fusion. Protein-binding partners of VAMP7 including the clathrin adaptors AP-3 (adaptor protein 3) and Hrb (HIV Rev-binding protein) are required for its correct intracellular localization and function. Overall, co-ordination of the activities of ESCRT, HOPS and SNARE complexes are required for efficient delivery of endocytosed macromolecules to lysosomes. Endosome–lysosome fusion results in a hybrid organelle from which lysosomes are re-formed. Defects in fusion and/or lysosome reformation occur in a number of lysosome storage diseases.
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Conference Article|
November 24 2010
Endosome–lysosome fusion
J. Paul Luzio;
J. Paul Luzio
1
1Cambridge Institute for Medical Research and Department of Clinical Biochemistry, University of Cambridge, Cambridge CB2 0XY, U.K.
1To whom correspondence should be addressed (email jpl10@cam.ac.uk).
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Sally R. Gray;
Sally R. Gray
1Cambridge Institute for Medical Research and Department of Clinical Biochemistry, University of Cambridge, Cambridge CB2 0XY, U.K.
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Nicholas A. Bright
Nicholas A. Bright
1Cambridge Institute for Medical Research and Department of Clinical Biochemistry, University of Cambridge, Cambridge CB2 0XY, U.K.
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Publisher: Portland Press Ltd
Received:
September 02 2010
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2010 Biochemical Society
2010
Biochem Soc Trans (2010) 38 (6): 1413–1416.
Article history
Received:
September 02 2010
Citation
J. Paul Luzio, Sally R. Gray, Nicholas A. Bright; Endosome–lysosome fusion. Biochem Soc Trans 1 December 2010; 38 (6): 1413–1416. doi: https://doi.org/10.1042/BST0381413
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