Clathrin-mediated post-fusion membrane retrieval influences the exocytic mode of endothelial Weibel-Palade bodies

Nicola Stevenson, Ian J. White, Jessica J. McCormack, Christopher Robinson, Daniel F. Cutler, Thomas D. Nightingale

Research output: Contribution to journalArticle (Academic Journal)peer-review

8 Citations (Scopus)
291 Downloads (Pure)

Abstract

Weibel-Palade bodies (WPBs), the storage organelles of endothelial cells, are essential to normal haemostatic and inflammatory responses. Their major constituent protein is von Willebrand factor (VWF) which, following stimulation with secretagogues, 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: WPBs then fuse with previously fused WPBs rather than the plasma membrane, leading, in turn, to the formation of structurally impaired tangled VWF strings.
Original languageEnglish
Pages (from-to)2591-2605
Number of pages15
JournalJournal of Cell Science
Volume130
Early online date3 Jul 2017
DOIs
Publication statusPublished - 1 Aug 2017

Keywords

  • Endocytosis
  • Endothelium
  • Weibel-Palade bodies
  • Exocytosis
  • Clathrin
  • Dynamin

Fingerprint Dive into the research topics of 'Clathrin-mediated post-fusion membrane retrieval influences the exocytic mode of endothelial Weibel-Palade bodies'. Together they form a unique fingerprint.

Cite this