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10.1161/ATVBAHA.117.310701

http://scihub22266oqcxt.onion/10.1161/ATVBAHA.117.310701
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suck abstract from ncbi


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pmid29880488
      Arterioscler+Thromb+Vasc+Biol 2018 ; 38 (7 ): 1549-1561
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  • Weibel-Palade Body Localized Syntaxin-3 Modulates Von Willebrand Factor Secretion From Endothelial Cells #MMPMID29880488
  • Schillemans M ; Karampini E ; van den Eshof BL ; Gangaev A ; Hofman M ; van Breevoort D ; Meems H ; Janssen H ; Mulder AA ; Jost CR ; Escher JC ; Adam R ; Carter T ; Koster AJ ; van den Biggelaar M ; Voorberg J ; Bierings R
  • Arterioscler Thromb Vasc Biol 2018[Jul]; 38 (7 ): 1549-1561 PMID29880488 show ga
  • OBJECTIVE: Endothelial cells store VWF (von Willebrand factor) in rod-shaped secretory organelles, called Weibel-Palade bodies (WPBs). WPB exocytosis is coordinated by a complex network of Rab GTPases, Rab effectors, and SNARE (soluble NSF attachment protein receptor) proteins. We have previously identified STXBP1 as the link between the Rab27A-Slp4-a complex on WPBs and the SNARE proteins syntaxin-2 and -3. In this study, we investigate the function of syntaxin-3 in VWF secretion. APPROACH AND RESULTS: In human umbilical vein endothelial cells and in blood outgrowth endothelial cells (BOECs) from healthy controls, endogenous syntaxin-3 immunolocalized to WPBs. A detailed analysis of BOECs isolated from a patient with variant microvillus inclusion disease, carrying a homozygous mutation in STX3(STX3(-/-)), showed a loss of syntaxin-3 protein and absence of WPB-associated syntaxin-3 immunoreactivity. Ultrastructural analysis revealed no detectable differences in morphology or prevalence of immature or mature WPBs in control versus STX3(-/-) BOECs. VWF multimer analysis showed normal patterns in plasma of the microvillus inclusion disease patient, and media from STX3(-/-) BOECs, together indicating WPB formation and maturation are unaffected by absence of syntaxin-3. However, a defect in basal as well as Ca(2+)- and cAMP-mediated VWF secretion was found in the STX3(-/-) BOECs. We also show that syntaxin-3 interacts with the WPB-associated SNARE protein VAMP8 (vesicle-associated membrane protein-8). CONCLUSIONS: Our data reveal syntaxin-3 as a novel WPB-associated SNARE protein that controls WPB exocytosis.
  • |*Exocytosis [MESH]
  • |Calcium/metabolism [MESH]
  • |Cells, Cultured [MESH]
  • |Cyclic AMP/metabolism [MESH]
  • |Endothelial Cells/*metabolism/ultrastructure [MESH]
  • |Human Umbilical Vein Endothelial Cells/metabolism [MESH]
  • |Humans [MESH]
  • |Malabsorption Syndromes/diagnosis/genetics/*metabolism [MESH]
  • |Microvilli/genetics/metabolism/*pathology [MESH]
  • |Mucolipidoses/diagnosis/genetics/*metabolism [MESH]
  • |Mutation [MESH]
  • |Qa-SNARE Proteins/genetics/*metabolism [MESH]
  • |R-SNARE Proteins/metabolism [MESH]
  • |Secretory Pathway [MESH]
  • |Signal Transduction [MESH]
  • |Weibel-Palade Bodies/*metabolism/ultrastructure [MESH]


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