|
 |
|
|
| The EMBO Journal
(1997) 16, 6182–6191, doi:10.1093/emboj/16.20.6182 |
|
| Cleavage of Rabaptin-5 blocks endosome fusion during apoptosis |
|
|
| Sabina C. Cosulich2, Hisanori Horiuchi3, Marino Zerial3, Paul R. Clarke2 and Philip G. Woodman1 |
|
|
1 Division of Biochemistry, School of Biological Sciences, University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK 2 Zeneca Laboratory of Molecular and Cellular Biology, School of Biological Sciences, University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK 3 European Molecular Biology Laboratory, Meyerhofstrasse 1, D69012 Heidelberg, Germany To whom correspondence should be addressed Philip G. Woodman, pwoodman@fs1.scg.man.ac.uk Received 6 February 1997; Revised 11 July 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. |
|
| Keywords: apoptosis, Bcl-2, caspase, fusion, Rabaptin-5 |
|
|
| |
| |
| |
 | Email link to a friend |
| |
 | Download PDF |
| |
 | Full text |
| |
| |
| |
 | Next article |
| |
 | Previous article |
| |
 | Table of contents |
| |
| |
 | Rights and permissions |
| |
 | Reprints |
| |
| |
| |
 Register for table of contents by email | |
| |
| |
| |
