Stevenson, NL;
White, IJ;
McCormack, JJ;
Robinson, C;
Cutler, DF;
Nightingale, TD;
(2017)
Clathrin-mediated post-fusion membrane retrieval influences the exocytic mode of endothelial Weibel-Palade bodies.
Journal of Cell Science
, 130
pp. 2591-2605.
10.1242/jcs.200840.
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Abstract
Weibel Palade bodies (WPB), the storage organelles of endothelial cells, are essential to normal haemostatic and inflammatory responses. Their major content protein is Von Willebrands factor (VWF) that, following secretagogue-stimulation, is released into the blood vessel lumen as large platelet-catching strings. This exocytosis changes the protein composition of the cell surface and also results in a net increase in the amount of plasma membrane. Compensatory endocytosis is thought to limit changes in cell size and retrieve fusion machinery and other misplaced integral membrane proteins following exocytosis, however little is known about the extent, timing, mechanism and precise function of compensatory endocytosis in endothelial cells. Using biochemical assays, live cell imaging and correlative spinning disk microscopy and transmission electron microscopy assays we provide the first in-depth high-resolution characterisation of this process. We provide a model of compensatory endocytosis based on rapid clathrin and dynamin mediated retrieval. Inhibition of this process results in a change of exocytic mode: WPB then fuse with previously fused WPB rather than the plasma membrane, leading in turn to formation of structurally-impaired tangled VWF strings.
| Type: | Article |
|---|---|
| Title: | Clathrin-mediated post-fusion membrane retrieval influences the exocytic mode of endothelial Weibel-Palade bodies |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1242/jcs.200840 |
| Publisher version: | http://doi.org/10.1242/jcs.200840 |
| Language: | English |
| Additional information: | Copyright © 2017. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
| Keywords: | Clathrin, Dynamin., Endocytosis, Endothelium, Exocytosis, Weibel Palade bodies |
| 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/1563299 |
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