A GBF1-Dependent Mechanism for Environmentally Responsive Regulation of ER-Golgi Transport

被引：35

作者：

Lopes-da-Silva, Mafalda ^{[1
,3
]}

McCormack, Jessica J. ^{[1
]}

Burden, Jemima J. ^{[2
]}

Harrison-Lavoie, Kimberly J. ^{[1
]}

Ferraro, Francesco ^{[1
]}

Cutler, Daniel F. ^{[1
]}

机构：

[1] UCL, MRC Lab Mol Cell Biol, Endothelial Cell Biol Lab, London, England

[2] UCL, MRC Lab Mol Cell Biol, Electron Microscopy Lab, London, England

[3] Univ Nova Lisboa, Fac Ciencias Med, NOVA Med Sch, CEDOC Chron Dis Res Ctr, Lisbon, Portugal

来源：

DEVELOPMENTAL CELL | 2019年 / 49卷 / 05期

关键词：

NUCLEOTIDE EXCHANGE FACTOR; VON-WILLEBRAND-FACTOR; ACTIVATED PROTEIN-KINASE; ADP-RIBOSYLATION FACTORS; WEIBEL-PALADE BODIES; FACTOR GBF1; DISTINCT FUNCTIONS; SECRETORY PATHWAY; ARF PROTEINS; COPI;

D O I：

10.1016/j.devcel.2019.04.006

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：786 / +

页数：22

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