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Cosulich SC
,
Horiuchi H
,
Zerial M
,
Clarke PR
,
Woodman PG
.
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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.
Beere,
Selective inhibition of topoisomerase II by ICRF-193 does not support a role for topoisomerase II activity in the fragmentation of chromatin during apoptosis of human leukemia cells.
1996, Pubmed
Beere,
Selective inhibition of topoisomerase II by ICRF-193 does not support a role for topoisomerase II activity in the fragmentation of chromatin during apoptosis of human leukemia cells.
1996,
Pubmed
Boldin,
Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death.
1996,
Pubmed
Brancolini,
Microfilament reorganization during apoptosis: the role of Gas2, a possible substrate for ICE-like proteases.
1995,
Pubmed
Bucci,
The small GTPase rab5 functions as a regulatory factor in the early endocytic pathway.
1992,
Pubmed
Bucci,
Rab5a is a common component of the apical and basolateral endocytic machinery in polarized epithelial cells.
1994,
Pubmed
Chinnaiyan,
The cell-death machine.
1996,
Pubmed
Chinnaiyan,
Molecular ordering of the cell death pathway. Bcl-2 and Bcl-xL function upstream of the CED-3-like apoptotic proteases.
1996,
Pubmed
Cosulich,
Bcl-2 regulates activation of apoptotic proteases in a cell-free system.
1996,
Pubmed
,
Xenbase
Diaz,
Vesicle fusion following receptor-mediated endocytosis requires a protein active in Golgi transport.
1989,
Pubmed
Duvall,
Macrophage recognition of cells undergoing programmed cell death (apoptosis).
1985,
Pubmed
Earnshaw,
Nuclear changes in apoptosis.
1995,
Pubmed
Enari,
Apoptosis by a cytosolic extract from Fas-activated cells.
1995,
Pubmed
Fearnhead,
An interleukin-1 beta-converting enzyme-like protease is a common mediator of apoptosis in thymocytes.
1995,
Pubmed
Gorvel,
rab5 controls early endosome fusion in vitro.
1991,
Pubmed
Jacobson,
Programmed cell death and Bcl-2 protection in the absence of a nucleus.
1994,
Pubmed
Jänicke,
Specific cleavage of the retinoblastoma protein by an ICE-like protease in apoptosis.
1996,
Pubmed
Kelly,
Secretion. A question of endosomes.
1993,
Pubmed
Kerr,
Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics.
1972,
Pubmed
Kiefer,
Modulation of apoptosis by the widely distributed Bcl-2 homologue Bak.
1995,
Pubmed
Lamaze,
Regulation of receptor-mediated endocytosis by Rho and Rac.
1996,
Pubmed
,
Xenbase
Lazebnik,
Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE.
1994,
Pubmed
Le Romancer,
Cleavage and inactivation of DNA-dependent protein kinase catalytic subunit during apoptosis in Xenopus egg extracts.
1996,
Pubmed
,
Xenbase
Martin,
Proteolysis of fodrin (non-erythroid spectrin) during apoptosis.
1995,
Pubmed
Martin,
Cell-free reconstitution of Fas-, UV radiation- and ceramide-induced apoptosis.
1995,
Pubmed
Martin,
Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl.
1995,
Pubmed
Muchmore,
X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death.
1996,
Pubmed
Murphy,
Endosome dynamics regulated by a Rho protein.
1996,
Pubmed
Muzio,
FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death--inducing signaling complex.
1996,
Pubmed
Na,
D4-GDI, a substrate of CPP32, is proteolyzed during Fas-induced apoptosis.
1996,
Pubmed
Newmeyer,
Cell-free apoptosis in Xenopus egg extracts: inhibition by Bcl-2 and requirement for an organelle fraction enriched in mitochondria.
1994,
Pubmed
,
Xenbase
Nicholson,
Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis.
1995,
Pubmed
Norman,
Characterization of a glucocorticoid-sensitive human lymphoid cell line.
1977,
Pubmed
Nuñez,
The Bcl-2 family of proteins: regulators of cell death and survival.
1994,
Pubmed
Oltvai,
Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death.
1993,
Pubmed
Raff,
Social controls on cell survival and cell death.
1992,
Pubmed
Reed,
Bcl-2 and the regulation of programmed cell death.
1994,
Pubmed
Rodriguez,
Multiple N-ethylmaleimide-sensitive components are required for endosomal vesicle fusion.
1994,
Pubmed
Rybin,
GTPase activity of Rab5 acts as a timer for endocytic membrane fusion.
1996,
Pubmed
Savill,
Vitronectin receptor-mediated phagocytosis of cells undergoing apoptosis.
1990,
Pubmed
Song,
DNA-dependent protein kinase catalytic subunit: a target for an ICE-like protease in apoptosis.
1996,
Pubmed
Stenmark,
Rabaptin-5 is a direct effector of the small GTPase Rab5 in endocytic membrane fusion.
1995,
Pubmed
Stenmark,
Inhibition of rab5 GTPase activity stimulates membrane fusion in endocytosis.
1994,
Pubmed
Tagaya,
Domain structure of an N-ethylmaleimide-sensitive fusion protein involved in vesicular transport.
1993,
Pubmed
Takahashi,
Cleavage of lamin A by Mch2 alpha but not CPP32: multiple interleukin 1 beta-converting enzyme-related proteases with distinct substrate recognition properties are active in apoptosis.
1996,
Pubmed
Thornberry,
A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes.
1992,
Pubmed
Tuomikoski,
Inhibition of endocytic vesicle fusion in vitro by the cell-cycle control protein kinase cdc2.
,
Pubmed
,
Xenbase
Ullrich,
Membrane association of Rab5 mediated by GDP-dissociation inhibitor and accompanied by GDP/GTP exchange.
1994,
Pubmed
Verhey,
Distinct signals in the GLUT4 glucose transporter for internalization and for targeting to an insulin-responsive compartment.
1995,
Pubmed
Warren,
Membrane partitioning during cell division.
1993,
Pubmed
Warren,
Recycling of transferrin receptors in A431 cells is inhibited during mitosis.
1984,
Pubmed
Weeks,
Immunoassays using acridinium esters.
1986,
Pubmed
Whyte,
Impairment of function in aging neutrophils is associated with apoptosis.
1993,
Pubmed
Wood,
Mitotic chromatin condensation in vitro using somatic cell extracts and nuclei with variable levels of endogenous topoisomerase II.
1990,
Pubmed
Woodman,
In vitro fusion of endocytic vesicles is inhibited by cyclin A-cdc2 kinase.
1993,
Pubmed
Woodman,
Fusion between vesicles from the pathway of receptor-mediated endocytosis in a cell-free system.
1988,
Pubmed
Woodman,
Fusion of endocytic vesicles in a cell-free system.
1989,
Pubmed
Wyllie,
Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation.
1980,
Pubmed
Yuan,
The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme.
1993,
Pubmed
