Stimulated release of intraluminal vesicles from Weibel-Palade bodies.


Journal

Blood
ISSN: 1528-0020
Titre abrégé: Blood
Pays: United States
ID NLM: 7603509

Informations de publication

Date de publication:
20 06 2019
Historique:
received: 11 09 2018
accepted: 06 02 2019
pubmed: 15 2 2019
medline: 10 1 2020
entrez: 15 2 2019
Statut: ppublish

Résumé

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 microdomains within WPBs. Extracellular antibody recycling studies showed that CD63 in WPB microdomains can originate from the plasma membrane. By cryo-electron tomography of frozen-hydrated endothelial cells, we identify internal vesicles as novel structural features of the WPB lumen. By live-cell fluorescence microscopy, we directly observe 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.

Identifiants

pubmed: 30760452
pii: S0006-4971(20)42476-0
doi: 10.1182/blood-2018-09-874552
pmc: PMC6624784
doi:

Substances chimiques

CD63 protein, human 0
Tetraspanin 30 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2707-2717

Subventions

Organisme : Medical Research Council
ID : MC_PC_13053
Pays : United Kingdom
Organisme : Cancer Research UK
ID : FC001143
Pays : United Kingdom

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2019 by The American Society of Hematology.

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Auteurs

James Streetley (J)

MRC National Institute for Medical Research, The Ridgeway, London, United Kingdom.

Ana-Violeta Fonseca (AV)

MRC National Institute for Medical Research, The Ridgeway, London, United Kingdom.

Jack Turner (J)

Structural Biology of Cells and Viruses Laboratory, Francis Crick Institute, London, United Kingdom; and.

Nikolai I Kiskin (NI)

MRC National Institute for Medical Research, The Ridgeway, London, United Kingdom.

Laura Knipe (L)

MRC National Institute for Medical Research, The Ridgeway, London, United Kingdom.

Peter B Rosenthal (PB)

MRC National Institute for Medical Research, The Ridgeway, London, United Kingdom.
Structural Biology of Cells and Viruses Laboratory, Francis Crick Institute, London, United Kingdom; and.

Tom Carter (T)

MRC National Institute for Medical Research, The Ridgeway, London, United Kingdom.
Molecular and Clinical Sciences Research Institute, St George's University, London, United Kingdom.

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Classifications MeSH