title: A two-tier Golgi-based control of organelle size underpins the functional plasticity of endothelial cells.
abstract: 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.
authors.affiliation: Endothelial Cell Biology Laboratory, Laboratory for Molecular and Cellular Biology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Francesco
authors.initials: F
authors.lastname: Ferraro
authors.affiliation: Translational Research Resource Center, Laboratory for Molecular and Cellular Biology, University College London, Gower Street, London WC1E 6BT, UK; Bioinformatics Image Core, Laboratory for Molecular and Cellular Biology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Janos
authors.initials: J
authors.lastname: Kriston-Vizi
authors.affiliation: Analytical Science Division, National Physical Laboratory, Hampton Road, Teddington, Middlesex TW11 0LW, UK.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Metcalf
authors.affiliation: Endothelial Cell Biology Laboratory, Laboratory for Molecular and Cellular Biology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Belen
authors.initials: B
authors.lastname: Martin-Martin
authors.affiliation: Translational Research Resource Center, Laboratory for Molecular and Cellular Biology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Jamie
authors.initials: J
authors.lastname: Freeman
authors.affiliation: Electron Microscopy Laboratory, Laboratory for Molecular and Cellular Biology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Jemima J
authors.initials: JJ
authors.lastname: Burden
authors.affiliation: Endothelial Cell Biology Laboratory, Laboratory for Molecular and Cellular Biology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: David
authors.initials: D
authors.lastname: Westmoreland
authors.affiliation: Endothelial Cell Biology Laboratory, Laboratory for Molecular and Cellular Biology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Clare E
authors.initials: CE
authors.lastname: Dyer
authors.affiliation: Analytical Science Division, National Physical Laboratory, Hampton Road, Teddington, Middlesex TW11 0LW, UK.
authors.forename: Alex E
authors.initials: AE
authors.lastname: Knight
authors.affiliation: Translational Research Resource Center, Laboratory for Molecular and Cellular Biology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Robin
authors.initials: R
authors.lastname: Ketteler
authors.affiliation: Endothelial Cell Biology Laboratory, Laboratory for Molecular and Cellular Biology, University College London, Gower Street, London WC1E 6BT, UK. Electronic address: d.cutler@ucl.ac.uk.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Cutler
mesh_terms: D001324:Autoantigens / Q000235:genetics; D002478:Cells, Cultured; D000077614:Golgi Matrix Proteins; D061307:Human Umbilical Vein Endothelial Cells / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics; D015739:Nocodazole / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering; D050257:Tubulin Modulators / Q000494:pharmacology; D020302:Weibel-Palade Bodies / Q000235:genetics / Q000502:physiology*; D021601:trans-Golgi Network / Q000378:metabolism*; D014841:von Willebrand Factor / Q000502:physiology*
chemical_list: D001324:Autoantigens; C122048:GORASP2 protein, human; D000077614:Golgi Matrix Proteins; C097741:Golgin subfamily A member 2; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D050257:Tubulin Modulators; C087574:macrogolgin; D014841:von Willebrand Factor; D015739:Nocodazole