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Stimulated release of intraluminal vesicles from Weibel-Palade Bodies

Streetley, J; Fonseca, A-V; Turner, J; Kiskin, KI; Knipe, L; Rosenthal, PR; Carter, TD (2019) Stimulated release of intraluminal vesicles from Weibel-Palade Bodies. BLOOD. ISSN 0006-4971 https://doi.org/10.1182/blood-2018-09-874552
SGUL Authors: Carter, Thomas David

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Abstract

Weibel-Palade bodies (WPBs) are secretory granules that contain von Willebrand factor and P-selectin, molecules that regulate hemostasis and inflammation respectively. The presence of CD63/LAMP3 in the limiting membrane of WPBs has led to their classification as lysosome-related organelles. Many lysosome-related organelles contain intraluminal vesicles (ILVs) enriched in CD63 that are secreted into the extracellular environment during cell activation to mediate intercellular communication. To date there are no reports that WPBs contain or release ILVs. By light microscopy and live-cell imaging we show that CD63 is enriched in micro-domains within WPBs. Extracellular antibody recycling studies showed that CD63 in WPB micro-domains can originate from the plasma membrane. By cryo-electron tomography of frozen-hydrated endothelial cells we identify internal vesicles as a novel structural feature of the WPB lumen. By live-cell fluorescence microscopy we observe directly the exocytotic release of EGFP-CD63 ILVs as discrete particles from individual WPBs. WPB exocytosis provides a novel route for release of ILVs during endothelial cell stimulation.

Item Type: Article
Additional Information: This research was originally published in Blood Online. Streetley, J; Fonseca, A-V; Turner, J; Kiskin, KI; Knipe, L; Rosenthal, PR; Carter, TD. Stimulated release of intraluminal vesicles from Weibel-Palade Bodies. Blood. Prepublished February 13, 2019; DOI 10.1182/blood-2018-09-874552.
Keywords: 1102 Cardiovascular Medicine And Haematology, 1103 Clinical Sciences, 1114 Paediatrics And Reproductive Medicine, Immunology
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: BLOOD
ISSN: 0006-4971
Dates:
DateEvent
13 February 2019Published Online
6 February 2019Accepted
Publisher License: Publisher's own licence
Projects:
Project IDFunderFunder ID
MC_PC_13053Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
FC001156Cancer Research UKhttp://dx.doi.org/10.13039/501100000289
FC001143Cancer Research UKhttp://dx.doi.org/10.13039/501100000289
FC001156Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
FC001143Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
FC001156Wellcome Trusthttp://dx.doi.org/10.13039/100004440
FC001143Wellcome Trusthttp://dx.doi.org/10.13039/100004440
URI: http://openaccess.sgul.ac.uk/id/eprint/110629
Publisher's version: https://doi.org/10.1182/blood-2018-09-874552

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