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Verfasst von:Schillemans, Maaike [VerfasserIn]   i
 Adam, Rüdiger [VerfasserIn]   i
Titel:Weibel-Palade body localized syntaxin-3 modulates von Willebrand Factor secretion fom endothelial cells
Verf.angabe:Maaike Schillemans, Ellie Karampini, Bart L. van den Eshof, Anastasia Gangaev, Menno Hofman, Dorothee van Breevoort, Henriët Meems, Hans Janssen, Aat A. Mulder, Carolina R. Jost, Johanna C. Escher, Rüdiger Adam, Tom Carter, Abraham J. Koster, Maartje van den Biggelaar, Jan Voorberg, Ruben Bierings
E-Jahr:2018
Jahr:1 Jul 2018
Umfang:13 S.
Fussnoten:Gesehen am 27.06.2019 ; Originally published 1 Jul 2018
Titel Quelle:Enthalten in: Arteriosclerosis, thrombosis, and vascular biology
Ort Quelle:Philadelphia, Pa. : Lippincott, Williams & Wilkins, 1981
Jahr Quelle:2018
Band/Heft Quelle:38(2018), 7, Seite 1549-1561
ISSN Quelle:1524-4636
 2330-9180
 2330-9199
Abstract: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 Ca2+- 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.
DOI:doi:10.1161/ATVBAHA.117.310701
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: http://dx.doi.org/10.1161/ATVBAHA.117.310701
 DOI: https://doi.org/10.1161/ATVBAHA.117.310701
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:1668047039
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