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Publication Detail
A two-tier Golgi-based control of organelle size underpins the functional plasticity of endothelial cells.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Ferraro F, Kriston-Vizi J, Metcalf DJ, Martin-Martin B, Freeman J, Burden JJ, Westmoreland D, Dyer CE, Knight AE, Ketteler R, Cutler DF
  • Publication date:
  • Pagination:
    292, 304
  • Journal:
    Dev Cell
  • Volume:
  • Issue:
  • Country:
    United States
  • PII:
  • Language:
  • Keywords:
    Autoantigens, Cells, Cultured, Human Umbilical Vein Endothelial Cells, Humans, Inflammation, Membrane Proteins, Nocodazole, RNA Interference, RNA, Small Interfering, Tubulin Modulators, Weibel-Palade Bodies, trans-Golgi Network, von Willebrand Factor
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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