A GBF1-Dependent Mechanism for Environmentally Responsive Regulation of ER-Golgi Transport.
Dev Cell
; 49(5): 786-801.e6, 2019 06 03.
Article
em En
| MEDLINE
| ID: mdl-31056345
ABSTRACT
How can anterograde membrane trafficking be modulated by physiological cues? A screen of Golgi-associated proteins revealed that the ARF-GEF GBF1 can selectively modulate the ER-Golgi trafficking of prohaemostatic von Willebrand factor (VWF) and extracellular matrix (ECM) proteins in human endothelial cells and in mouse fibroblasts. The relationship between levels of GBF1 and the trafficking of VWF into forming secretory granules confirmed GBF1 is a limiting factor in this process. Further, GBF1 activation by AMPK couples its control of anterograde trafficking to physiological cues; levels of glucose control GBF1 activation in turn modulating VWF trafficking into secretory granules. GBF1 modulates both ER and TGN exit, the latter dramatically affecting the size of the VWF storage organelles, thereby influencing the hemostatic capacity of the endothelium. The role of AMPK as a central integrating element of cellular pathways with intra- and extra-cellular cues can now be extended to modulation of the anterograde secretory pathway.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator de von Willebrand
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Fatores de Ribosilação do ADP
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Fator 1 de Ribosilação do ADP
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Fatores de Troca do Nucleotídeo Guanina
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Retículo Endoplasmático
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Proteínas Quinases Ativadas por AMP
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Complexo de Golgi
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Dev Cell
Assunto da revista:
EMBRIOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article