PXD068012

PXD068012 is an original dataset announced via ProteomeXchange.

Title	VE-cadherin interaction proteomics identifies ARVCF as a key stabilizer of endothelial adherens junctions
Description	The endothelial cells lining the vascular wall maintain a selective barrier between blood and tissue. Structural connections between these endothelial cells are formed through vascular endothelial (VE)-cadherin-based adherens junctions. The extracellular domain of VE-cadherin forms homotypic bonds between neighboring cells, while its intracellular domain connects to the actin cytoskeleton via a conserved protein complex including α-, ß- and p120-catenins. Whether additional proteins bind to VE-cadherin and contribute to endothelial junction integrity remains unclear. By using mass spectrometry after VE-cadherin immunoprecipitations from human endothelial cells, we have determined the molecular interactions with VE-cadherin. The proteomics identified a core VE-cadherin interactome, consisting of nine proteins, which bind to VE-cadherin even in the absence of tyrosine phosphorylation of its intracellular domain. The core VE-cadherin interactome includes the known catenin proteins as well as four new interactors: ARVCF, ARHGAP23, KEAP1 and NGLY1. Co-immunoprecipitation and co-localization experiments verified that the VE-cadherin-binding protein ARVCF is an important component of endothelial adherens junctions. ARVCF binds to a selective pool of VE-cadherin proteins during junction maturation that is unbound from p120-catenin, through a mechanism involving the C-terminal intrinsically disordered regions of ARVCF. Depletion of ARVCF results in loss of endothelial barrier function and impairs collective cell migration. Accordingly, ARVCF is needed for VE-cadherin-based junction stabilization. Together, our results demonstrate that ARVCF is a key regulator of VE-cadherin to safeguard junctional stability and endothelial integrity.
HostingRepository	PRIDE
AnnounceDate	2026-03-18
AnnouncementXML	Submission_2026-03-18_03:25:03.121.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Arie Hoogendijk
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-02 22:56:41	ID requested
⏵ 1	2026-03-18 03:25:03	announced

Dataset with its publication pending

submitter keyword: VE-cadherin interaction proteomics identifies ARVCF as a key stabilizer of endothelial adherens junctions

Dr Maartje van den Biggelaar
contact affiliation	Department of Molecular Hematology, Sanquin Research, Amsterdam
contact email	m.vandenbiggelaar@sanquin.nl
lab head
Arie Hoogendijk
contact affiliation	Sanquin Research, Amsterdam
contact email	a.hoogendijk@sanquin.nl
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/03/PXD068012

PRIDE project URI

• PRIDE
  1. PXD068012
     1. Label: PRIDE project
     2. Name: VE-cadherin interaction proteomics identifies ARVCF as a key stabilizer of endothelial adherens junctions