title: Weibel-Palade body size modulates the adhesive activity of its von Willebrand Factor cargo in cultured endothelial cells.
abstract: Changes in the size of cellular organelles are often linked to modifications in their function. Endothelial cells store von Willebrand Factor (vWF), a glycoprotein essential to haemostasis in Weibel-Palade bodies (WPBs), cigar-shaped secretory granules that are generated in a wide range of sizes. We recently showed that forcing changes in the size of WPBs modifies the activity of this cargo. We now find that endothelial cells treated with statins produce shorter WPBs and that the vWF they release at exocytosis displays a reduced capability to recruit platelets to the endothelial cell surface. Investigating other functional consequences of size changes of WPBs, we also report that the endothelial surface-associated vWF formed at exocytosis recruits soluble plasma vWF and that this process is reduced by treatments that shorten WPBs, statins included. These results indicate that the post-exocytic adhesive activity of vWF towards platelets and plasma vWF at the endothelial surface reflects the size of their storage organelle. Our findings therefore show that changes in WPB size, by influencing the adhesive activity of its vWF cargo, may represent a novel mode of regulation of platelet aggregation at the vascular wall.
authors: MRC Laboratory for Molecular Cell Biology, UCL, Gower Street, London, WC1E 6BT, United Kingdom.
authors: Francesco
authors: F
authors: Ferraro
authors: MRC Laboratory for Molecular Cell Biology, UCL, Gower Street, London, WC1E 6BT, United Kingdom.
authors: Silva
authors: S
authors: Mafalda Lopes da
authors: MRC Laboratory for Molecular Cell Biology, UCL, Gower Street, London, WC1E 6BT, United Kingdom.|Imaging Informatics Division, Bioinformatics Institute, A*STAR 30 Biopolis Street #07-01, Matrix, Singapore 138671.
authors: William
authors: W
authors: Grimes
authors: Imaging Informatics Division, Bioinformatics Institute, A*STAR 30 Biopolis Street #07-01, Matrix, Singapore 138671.
authors: Hwee Kuan
authors: HK
authors: Lee
authors: MRC Laboratory for Molecular Cell Biology, UCL, Gower Street, London, WC1E 6BT, United Kingdom.
authors: Robin
authors: R
authors: Ketteler
authors: MRC Laboratory for Molecular Cell Biology, UCL, Gower Street, London, WC1E 6BT, United Kingdom.
authors: Janos
authors: J
authors: Kriston-Vizi
authors: MRC Laboratory for Molecular Cell Biology, UCL, Gower Street, London, WC1E 6BT, United Kingdom.
authors: Daniel F
authors: DF
authors: Cutler
mesh_terms: D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000235:genetics; D002462:Cell Membrane / Q000235:genetics; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D005089:Exocytosis / Q000235:genetics*; D006801:Humans; D015388:Organelles / Q000378:metabolism; D022142:Secretory Vesicles / Q000235:genetics / Q000378:metabolism; D020302:Weibel-Palade Bodies / Q000378:metabolism*; D014841:von Willebrand Factor / Q000235:genetics* / Q000378:metabolism
chemical_list: D014841:von Willebrand Factor