In mammalian cells, endocytosed cargo that is internalized through clathrin-coated pits/vesicles passes through early endosomes and then to late endosomes, before delivery to lysosomes for degradation by proteases. Late endosomes are MVBs (multivesicular bodies) with ubiquitinated membrane proteins destined for lysosomal degradation being sorted into their luminal vesicles by the ESCRT (endosomal sorting complex required for transport) machinery. Cargo is delivered from late endosomes to lysosomes by kissing and direct fusion. These processes have been studied in live cell experiments and a cell-free system. Late endosome–lysosome fusion is preceded by tethering that probably requires mammalian orthologues of the yeast HOPS (homotypic fusion and vacuole protein sorting) complex. Heterotypic late endosome–lysosome membrane fusion is mediated by a trans-SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein receptor) complex comprising Syntaxin7, Vti1b, Syntaxin8 and VAMP7 (vesicle-associated membrane protein 7). This differs from the trans-SNARE complex required for homotypic late endosome fusion in which VAMP8 replaces VAMP7. VAMP7 is also required for lysosome fusion with the plasma membrane and its retrieval from the plasma membrane to lysosomes is mediated by its folded N-terminal longin domain. Co-ordinated interaction of the ESCRT, HOPS and SNARE complexes is required for cargo delivery to lysosomes.
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Conference Article|
September 21 2009
The delivery of endocytosed cargo to lysosomes
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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Michael D.J. Parkinson;
Michael D.J. Parkinson
1Cambridge Institute for Medical Research and Department of Clinical Biochemistry, University of Cambridge, Cambridge CB2 0XY, U.K.
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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:
June 22 2009
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2009 Biochemical Society
2009
Biochem Soc Trans (2009) 37 (5): 1019–1021.
Article history
Received:
June 22 2009
Citation
J. Paul Luzio, Michael D.J. Parkinson, Sally R. Gray, Nicholas A. Bright; The delivery of endocytosed cargo to lysosomes. Biochem Soc Trans 1 October 2009; 37 (5): 1019–1021. doi: https://doi.org/10.1042/BST0371019
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