Results

RDF/XMLNTriplesTurtleShow queryShare ▶
SubjectPredicateObject
http://purl.uniprot.org/citations/29880488http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/29880488http://www.w3.org/2000/01/rdf-schema#comment"

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."xsd:string
http://purl.uniprot.org/citations/29880488http://purl.org/dc/terms/identifier"doi:10.1161/atvbaha.117.310701"xsd:string
http://purl.uniprot.org/citations/29880488http://purl.uniprot.org/core/author"Koster A.J."xsd:string
http://purl.uniprot.org/citations/29880488http://purl.uniprot.org/core/author"Janssen H."xsd:string
http://purl.uniprot.org/citations/29880488http://purl.uniprot.org/core/author"Bierings R."xsd:string
http://purl.uniprot.org/citations/29880488http://purl.uniprot.org/core/author"Mulder A.A."xsd:string
http://purl.uniprot.org/citations/29880488http://purl.uniprot.org/core/author"Voorberg J."xsd:string
http://purl.uniprot.org/citations/29880488http://purl.uniprot.org/core/author"Adam R."xsd:string
http://purl.uniprot.org/citations/29880488http://purl.uniprot.org/core/author"Carter T."xsd:string
http://purl.uniprot.org/citations/29880488http://purl.uniprot.org/core/author"Escher J.C."xsd:string
http://purl.uniprot.org/citations/29880488http://purl.uniprot.org/core/author"Jost C.R."xsd:string
http://purl.uniprot.org/citations/29880488http://purl.uniprot.org/core/author"van den Biggelaar M."xsd:string
http://purl.uniprot.org/citations/29880488http://purl.uniprot.org/core/author"Meems H."xsd:string
http://purl.uniprot.org/citations/29880488http://purl.uniprot.org/core/author"van Breevoort D."xsd:string
http://purl.uniprot.org/citations/29880488http://purl.uniprot.org/core/author"Gangaev A."xsd:string
http://purl.uniprot.org/citations/29880488http://purl.uniprot.org/core/author"Hofman M."xsd:string
http://purl.uniprot.org/citations/29880488http://purl.uniprot.org/core/author"Karampini E."xsd:string
http://purl.uniprot.org/citations/29880488http://purl.uniprot.org/core/author"Schillemans M."xsd:string
http://purl.uniprot.org/citations/29880488http://purl.uniprot.org/core/author"van den Eshof B.L."xsd:string
http://purl.uniprot.org/citations/29880488http://purl.uniprot.org/core/date"2018"xsd:gYear
http://purl.uniprot.org/citations/29880488http://purl.uniprot.org/core/name"Arterioscler Thromb Vasc Biol"xsd:string
http://purl.uniprot.org/citations/29880488http://purl.uniprot.org/core/pages"1549-1561"xsd:string
http://purl.uniprot.org/citations/29880488http://purl.uniprot.org/core/title"Weibel-Palade Body Localized Syntaxin-3 Modulates Von Willebrand Factor Secretion From Endothelial Cells."xsd:string
http://purl.uniprot.org/citations/29880488http://purl.uniprot.org/core/volume"38"xsd:string
▶