Membrane traffic to and from lysosomes

J Paul Luzio; Paul R Pryor; Sally R Gray; Matthew J Gratian; Robert C Piper; Nicholas A Bright

doi:10.1042/bss0720077

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Journal article

Membrane traffic to and from lysosomes

J Paul Luzio, Paul R Pryor, Sally R Gray, Matthew J Gratian, Robert C Piper and Nicholas A Bright

Biochemical Society Symposia, Vol.72(72), pp.77-86

2005

DOI: 10.1042/bss0720077

PMID: 15649132

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Abstract

In the late endocytic pathway, it has been proposed that endocytosed macromolecules are delivered to a proteolytic environment by 'kiss-and-run' events or direct fusion between late endosomes and lysosomes. To test whether the fusion hypothesis accounts for delivery to lysosomes in living cells, we have used confocal microscopy to examine content mixing between lysosomes loaded with rhodamine-dextran and endosomes subsequently loaded with Oregon-Green-dextran. Both kissing and explosive fusion events were recorded. Data from cell-free content-mixing assays have suggested that fusion is initiated by tethering, which leads to formation of a trans-SNARE (soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor) protein complex and then release of lumenal Ca(2+), followed by membrane bilayer fusion. We have shown that the R-SNARE (arginine-containing SNARE) protein VAMP (vesicle-associated membrane protein) 7 is necessary for heterotypic fusion between late endosomes and lysosomes, whereas a different R-SNARE, VAMP 8 is required for homotypic fusion of late endosomes. After fusion of lysosomes with late endosomes, lysosomes are re-formed from the resultant hybrid organelles, a process requiring condensation of content and the removal/recycling of some membrane proteins.

Animals

Biological Transport, Active

Endocytosis

Endosomes - metabolism

In Vitro Techniques

Lysosomes - metabolism

Membrane Fusion

Membrane Proteins - metabolism

Models, Biological

Rats

Details

Title: Subtitle: Membrane traffic to and from lysosomes
Creators: J Paul Luzio - University of Cambridge
Paul R Pryor - University of Cambridge
Sally R Gray - University of Cambridge
Matthew J Gratian - University of Cambridge
Robert C Piper - University of Iowa
Nicholas A Bright - University of Cambridge
Resource Type: Journal article
Publication Details: Biochemical Society Symposia, Vol.72(72), pp.77-86
DOI: 10.1042/bss0720077
PMID: 15649132
ISSN: 0067-8694
eISSN: 1744-1439
Grant note: R01 GM058202 / NIGMS NIH HHS
Language: English
Date published: 2005
Academic Unit: Molecular Physiology and Biophysics; Medicine Administration; Internal Medicine
Record Identifier: 9984297492202771

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