Regulation of cell death by recycling endosomes and golgi membrane dynamics via a pathway involving Src-family kinases, Cdc42 and Rab11a.
Mol Biol Cell
; 20(18): 4091-106, 2009 Sep.
Article
em En
| MEDLINE
| ID: mdl-19641023
ABSTRACT
Actin dynamics and membrane trafficking influence cell commitment to programmed cell death through largely undefined mechanisms. To investigate how actin and recycling endosome (RE) trafficking can engage death signaling, we studied the death program induced by the adenovirus early region 4 open reading frame 4 (E4orf4) protein as a model. We found that in the early stages of E4orf4 expression, Src-family kinases (SFKs), Cdc42, and actin perturbed the organization of the endocytic recycling compartment and promoted the transport of REs to the Golgi apparatus, while inhibiting recycling of protein cargos to the plasma membrane. The resulting changes in Golgi membrane dynamics that relied on actin-regulated Rab11a membrane trafficking triggered scattering of Golgi membranes and contributed to the progression of cell death. A similar mobilization of RE traffic mediated by SFKs, Cdc42 and Rab11a also contributed to Golgi fragmentation and to cell death progression in response to staurosporine, in a caspase-independent manner. Collectively, these novel findings suggest that diversion of RE trafficking to the Golgi complex through a pathway involving SFKs, Cdc42, and Rab11a plays a general role in death signaling by mediating regulated changes in Golgi dynamics.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Endossomos
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Quinases da Família src
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Proteínas rab de Ligação ao GTP
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Proteína cdc42 de Ligação ao GTP
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Endocitose
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Complexo de Golgi
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Membranas Intracelulares
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article