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A Two-Tier Golgi-Based Control of Organelle Size Underpins the Functional Plasticity of Endothelial Cells

Weibel-Palade bodies (WPBs), endothelial-specific secretory granules that are central to primary hemostasis and inflammation, occur in dimensions ranging between 0.5 and 5 μm. How their size is determined and whether it has a functional relevance are at present unknown. Here, we provide evidence for...

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Autores principales: Ferraro, Francesco, Kriston-Vizi, Janos, Metcalf, Daniel J., Martin-Martin, Belen, Freeman, Jamie, Burden, Jemima J., Westmoreland, David, Dyer, Clare E., Knight, Alex E., Ketteler, Robin, Cutler, Daniel F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4022834/
https://www.ncbi.nlm.nih.gov/pubmed/24794632
http://dx.doi.org/10.1016/j.devcel.2014.03.021
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author Ferraro, Francesco
Kriston-Vizi, Janos
Metcalf, Daniel J.
Martin-Martin, Belen
Freeman, Jamie
Burden, Jemima J.
Westmoreland, David
Dyer, Clare E.
Knight, Alex E.
Ketteler, Robin
Cutler, Daniel F.
author_facet Ferraro, Francesco
Kriston-Vizi, Janos
Metcalf, Daniel J.
Martin-Martin, Belen
Freeman, Jamie
Burden, Jemima J.
Westmoreland, David
Dyer, Clare E.
Knight, Alex E.
Ketteler, Robin
Cutler, Daniel F.
author_sort Ferraro, Francesco
collection PubMed
description Weibel-Palade bodies (WPBs), endothelial-specific secretory granules that are central to primary hemostasis and inflammation, occur in dimensions ranging between 0.5 and 5 μm. How their size is determined and whether it has a functional relevance are at present unknown. Here, we provide evidence for a dual role of the Golgi apparatus in controlling the size of these secretory carriers. At the ministack level, cisternae constrain the size of nanostructures (“quanta”) of von Willebrand factor (vWF), the main WPB cargo. The ribbon architecture of the Golgi then allows copackaging of a variable number of vWF quanta within the continuous lumen of the trans-Golgi network, thereby generating organelles of different sizes. Reducing the WPB size abates endothelial cell hemostatic function by drastically diminishing platelet recruitment, but, strikingly, the inflammatory response (the endothelial capacity to engage leukocytes) is unaltered. Size can thus confer functional plasticity to an organelle by differentially affecting its activities.
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spelling pubmed-40228342014-05-19 A Two-Tier Golgi-Based Control of Organelle Size Underpins the Functional Plasticity of Endothelial Cells Ferraro, Francesco Kriston-Vizi, Janos Metcalf, Daniel J. Martin-Martin, Belen Freeman, Jamie Burden, Jemima J. Westmoreland, David Dyer, Clare E. Knight, Alex E. Ketteler, Robin Cutler, Daniel F. Dev Cell Article Weibel-Palade bodies (WPBs), endothelial-specific secretory granules that are central to primary hemostasis and inflammation, occur in dimensions ranging between 0.5 and 5 μm. How their size is determined and whether it has a functional relevance are at present unknown. Here, we provide evidence for a dual role of the Golgi apparatus in controlling the size of these secretory carriers. At the ministack level, cisternae constrain the size of nanostructures (“quanta”) of von Willebrand factor (vWF), the main WPB cargo. The ribbon architecture of the Golgi then allows copackaging of a variable number of vWF quanta within the continuous lumen of the trans-Golgi network, thereby generating organelles of different sizes. Reducing the WPB size abates endothelial cell hemostatic function by drastically diminishing platelet recruitment, but, strikingly, the inflammatory response (the endothelial capacity to engage leukocytes) is unaltered. Size can thus confer functional plasticity to an organelle by differentially affecting its activities. Cell Press 2014-05-12 /pmc/articles/PMC4022834/ /pubmed/24794632 http://dx.doi.org/10.1016/j.devcel.2014.03.021 Text en © 2014 The Authors http://creativecommons.org/licenses/by/3.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Ferraro, Francesco
Kriston-Vizi, Janos
Metcalf, Daniel J.
Martin-Martin, Belen
Freeman, Jamie
Burden, Jemima J.
Westmoreland, David
Dyer, Clare E.
Knight, Alex E.
Ketteler, Robin
Cutler, Daniel F.
A Two-Tier Golgi-Based Control of Organelle Size Underpins the Functional Plasticity of Endothelial Cells
title A Two-Tier Golgi-Based Control of Organelle Size Underpins the Functional Plasticity of Endothelial Cells
title_full A Two-Tier Golgi-Based Control of Organelle Size Underpins the Functional Plasticity of Endothelial Cells
title_fullStr A Two-Tier Golgi-Based Control of Organelle Size Underpins the Functional Plasticity of Endothelial Cells
title_full_unstemmed A Two-Tier Golgi-Based Control of Organelle Size Underpins the Functional Plasticity of Endothelial Cells
title_short A Two-Tier Golgi-Based Control of Organelle Size Underpins the Functional Plasticity of Endothelial Cells
title_sort two-tier golgi-based control of organelle size underpins the functional plasticity of endothelial cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4022834/
https://www.ncbi.nlm.nih.gov/pubmed/24794632
http://dx.doi.org/10.1016/j.devcel.2014.03.021
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