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Cleavage of rabaptin-5 blocks endosome fusion during apoptosis.
- Source :
-
The EMBO journal [EMBO J] 1997 Oct 15; Vol. 16 (20), pp. 6182-91. - Publication Year :
- 1997
-
Abstract
- Cells undergoing apoptosis exhibit striking changes in membrane organization, including plasma membrane blebbing and invagination, vacuolation and fragmentation of organelles, and alterations in the surface expression of receptors. The underlying mechanisms for these changes are unknown, though alterations in vesicular fusion are likely to play a role. Using a cell-free system based on Xenopus laevis egg extracts we have found that endosome fusion is blocked during apoptosis. Inhibition of fusion is prevented by Bcl-2 or Bcl-xL, two negative regulators of apoptosis, or by specific inhibitors of members of the caspase family of apoptotic proteases. Selective cleavage of Rabaptin-5, an essential and rate-limiting component of endosome fusion, is responsible for the loss of fusion activity. Cleavage of Rabaptin-5 also occurs in cellular models for apoptosis. These results suggest that inactivation of Rabaptin-5 and inhibition of vesicle transport lead to fragmentation of endosomes and inhibition of the endocytic pathway during the execution phase of apoptosis. We propose that parallel changes to other membrane transport pathways would give rise to general membrane fragmentation in apoptotic cells. These changes are likely to play an important role in the generation of apoptotic bodies and their recognition by phagocytosing cells.
- Subjects :
- Animals
Biological Transport
Cell-Free System
Cysteine Proteinase Inhibitors pharmacology
Endocytosis
Humans
Ovum
Proto-Oncogene Proteins c-bcl-2 metabolism
Substrate Specificity
Xenopus
Xenopus Proteins
bcl-X Protein
Apoptosis physiology
Cysteine Endopeptidases metabolism
Endosomes physiology
Membrane Fusion drug effects
Membrane Proteins metabolism
Vesicular Transport Proteins
Subjects
Details
- Language :
- English
- ISSN :
- 0261-4189
- Volume :
- 16
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- The EMBO journal
- Publication Type :
- Academic Journal
- Accession number :
- 9321397
- Full Text :
- https://doi.org/10.1093/emboj/16.20.6182