PXD006176

PXD006176 is an original dataset announced via ProteomeXchange.

Title	Syntaxin-3 is a Weibel-Palade body localized SNARE protein that regulates Von Willebrand factor secretion from endothelial cells
Description	Endothelial cells store von Willebrand factor (VWF) 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 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. In human umbilical vein endothelial cells (HUVECs) 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 (MVID), 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 MVID patient, and media from STX3-/- BOECs, together indicating WPB formation and maturation are unaffected by absence of syntaxin-3. However, a clear defect in Ca2+ and cAMP-mediated VWF secretion was found in the STX3-/- BOECs. Co-immunoprecipitation studies showed that syntaxin-3 associates with the WPB SNAREs SNAP23 and VAMP8. Our data reveal syntaxin-3 as a novel WPB-associated SNARE controlling VWF secretion and highlight the complex regulation of WPB exocytosis by multiple SNARE complexes.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:05:05.391.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Bart van den Eshof
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion ETD

Revision	Datetime	Status	ChangeLog Entry
0	2017-03-27 01:51:11	ID requested
1	2018-07-04 02:54:12	announced
⏵ 2	2024-10-22 04:05:06	announced	2024-10-22: Updated project metadata.

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, Weibel-Palade Body Localized Syntaxin-3 Modulates Von Willebrand Factor Secretion From Endothelial Cells. Arterioscler Thromb Vasc Biol, 38(7):1549-1561(2018) [pubmed]

10.1161/atvbaha.117.310701;

curator keyword: Biological

submitter keyword: endothelial cells, proteomics, Weibel-Palade body, SNARE machinery, syntaxin-3, Von Willebrand factor

Maartje van den Biggelaar
contact affiliation	Plasma Proteins, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
contact email	m.vandenbiggelaar@sanquin.nl
lab head
Bart van den Eshof
contact affiliation	Sanquin Research
contact email	bartvdeshof@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD006176
     1. Label: PRIDE project
     2. Name: Syntaxin-3 is a Weibel-Palade body localized SNARE protein that regulates Von Willebrand factor secretion from endothelial cells