Lopes-da-Silva, M;
McCormack, JJ;
Burden, JJ;
Harrison-Lavoie, KJ;
Ferraro, F;
Cutler, DF;
(2019)
A GBF1-Dependent Mechanism for Environmentally Responsive Regulation of ER-Golgi Transport.
Developmental Cell
, 49
(5)
pp. 786-801.
10.1016/j.devcel.2019.04.006.
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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.
| Type: | Article |
|---|---|
| Title: | A GBF1-Dependent Mechanism for Environmentally Responsive Regulation of ER-Golgi Transport |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.devcel.2019.04.006 |
| Publisher version: | https://doi.org/10.1016/j.devcel.2019.04.006 |
| Language: | English |
| Additional information: | Copyright © 2019 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | AMPK, GBF1, Golgi, anterograde trafficking, collagen, endothelial cells, hemostasis, organelle size, secretion, von Willebrand factor |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10073713 |
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