PXD013194

PXD013194 is an original dataset announced via ProteomeXchange.

Title	Proximity proteomics of endothelial Weibel-Palade bodies identifies novel regulator of VWF secretion
Description	Weibel-Palade bodies (WPB) are unique secretory organelles of endothelial cells that store factors regulating vascular haemostasis and local inflammation. Endothelial activation triggers the acute exocytosis of WPB, leading to the surface presentation of adhesion molecules relevant for leukocyte rolling (P-selectin) and platelet plug formation (von-Willebrand factor, VWF). Despite its role as an important secretory organelle, a comprehensive compilation of WPB-associated factors has not been carried out. We addressed this by a proximity proteomics approach employing the peroxidase APEX2 coupled to two known WPB-associated proteins, the RabGTPases Rab3b and Rab27a. We show that APEX2-Rab3b/27a fusion constructs are correctly targeted to WPB and that proteins in their close proximity can be biotinylated through the WPB-recruited APEX2. Mass spectrometry analysis of the biotinylated proteins identified 183 WPB-associated proteins. While some of the factors identified have been reported before to localize to WPB, the majority comprises proteins not previously associated with WPB biology. These include the SNARE-interacting protein Munc13-2, which specifically localizes to WPB and serves as a novel factor promoting histamine-evoked WPB exocytosis and VWF secretion.
HostingRepository	PRIDE
AnnounceDate	2019-07-11
AnnouncementXML	Submission_2019-07-11_01:23:30.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hannes Drexler
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-03-22 05:10:28	ID requested
⏵ 1	2019-07-11 01:23:31	announced

Holthenrich A, Drexler HCA, Chehab T, Na, ß J, Gerke V, Proximity proteomics of endothelial Weibel-Palade bodies identifies novel regulator of von Willebrand factor secretion. Blood, 134(12):979-982(2019) [pubmed]

submitter keyword: human, endothelial cells, Weibel-Palade bodies, von-Willebrand factor, proximity labeling, biotinylation, LC-MSMS

Hannes C. A. Drexle5r
contact affiliation	Max Planck Institut or Molecular Biomedicine Bioanyltical Mass Spectrometry Röntgenstr. 20 48149 Münster Germany
contact email	hannes.drexler@mpi-muenster.mpg.de
lab head
Hannes Drexler
contact affiliation	Bioanalytical Mass Spectrometry
contact email	hannes.drexler@mpi-muenster.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD013194
     1. Label: PRIDE project
     2. Name: Proximity proteomics of endothelial Weibel-Palade bodies identifies novel regulator of VWF secretion