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Publication Detail
Type II PI4-kinases control Weibel-Palade body biogenesis and von Willebrand factor structure in human endothelial cells
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Article
  • Authors:
    O'Connor MN, da Silva ML, Kriston-Vizi J, White IJ, Al-Shawi R, Simons JP, Mössinger J, Haucke V, Cutler DF
  • Publication date:
    15/05/2016
  • Pagination:
    2096, 2105
  • Journal:
    Journal of Cell Science
  • Volume:
    129
  • Issue:
    10
  • Status:
    Published
  • Print ISSN:
    0021-9533
Abstract
© 2016.Weibel-Palade bodies (WPBs) are endothelial storage organelles that mediate the release of molecules involved in thrombosis, inflammation and angiogenesis, including the pro-thrombotic glycoprotein von Willebrand factor (VWF). Although many protein components required for WPB formation and function have been identified, the role of lipids is almost unknown. We examined two key phosphatidylinositol kinases that control phosphatidylinositol 4-phosphate levels at the trans-Golgi network, the site of WPB biogenesis. RNA interference of the type II phosphatidylinositol 4-kinases PI4KIIα and PI4KIIβ in primary human endothelial cells leads to formation of an increased proportion of short WPB with perturbed packing of VWF, as exemplified by increased exposure of antibody-binding sites. When stimulated with histamine, these cells release normal levels of VWF yet, under flow, form very few plateletcatching VWF strings. In PI4KIIα-deficient mice, immuno-microscopy revealed that VWF packaging is also perturbed and these mice exhibit increased blood loss after tail cut compared to controls. This is the first demonstration that lipid kinases can control the biosynthesis of VWF and the formation of WPBs that are capable of full haemostatic function.
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