PXD067112-1

PXD067112 is an original dataset announced via ProteomeXchange.

Title	Endocytic Turnover of Endothelial Cell-Membrane Proteins as a Driver of Blood Brain Barrier Specialization and Dysfunction
Description	The blood-brain barrier (BBB), formed primarily by specialized brain endothelial cells (BEC), exerts essential functions for proper brain activity, including nutrient transport, signal transduction, immune cell transmigration and pathogen restriction. While these functions are known to be regulated by the identity and abundance (i.e. composition) of cell-membrane proteins, a parameter which remains underexplored is how protein endocytic turnover rate (ETOR)—the rate of protein internalization from the cell membrane— governs BBB physiology. Employing high-throughput in vitro proteomics, we quantify the ETOR of large protein arrays (c. 1000 individual proteins) across endothelial phenotypes and pathological states to examine the mechanisms driving BBB specialization and the changes underlying BBB dysfunction. We find that BEC possess a specialized ETOR profile which differentiates them from peripheral endothelial cells beyond their cell-membrane protein composition. In addition, we demonstrate that inflammatory conditions disrupt the endocytic rates of BEC to a greater degree than disruptions in protein abundance, shifting the specialized ETOR profile of BEC towards a peripheral phenotype. Furthermore, we demonstrate that, while inflammation-induced changes in protein abundance identify proteins strongly involved in immune response, inflammation-induced changes in ETOR identifies proteins strongly involved in vasculature remodelling. Together, our results indicate that the ETOR of cell-membrane proteins is an important parameter driving the specialization of the BBB which becomes disrupted during pathological conditions independently of cell-membrane protein composition. Furthermore, it highlights that ETOR changes identify pathological mechanisms underlying BBB dysfunction not identified by changes in protein abundance.
HostingRepository	PRIDE
AnnounceDate	2026-05-15
AnnouncementXML	Submission_2026-05-15_06:52:10.374.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marta Vilaseca
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: NEWT:10116;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-08 00:27:15	ID requested
⏵ 1	2026-05-15 06:52:10	announced

Dataset with its publication pending

submitter keyword: blood-brain barrier, brain endothelial cells, endocytic turnover rate

Marta Vilaseca
contact affiliation	Mass Spectrometry & Proteomics Core Facility (MSPCF) Institute for Research in Biomedicine (IRB Barcelona) Barcelona Institute of Science and Technology (BIST) C/ Baldiri Reixac, 10-12 08028 Barcelona - Spain.
contact email	masspe@irbbarcelona.org
lab head
Marta Vilaseca
contact affiliation	Mass Spectrometry & Proteomics Core Facility (MSPCF) Institute for Research in Biomedicine (IRB Barcelona) Barcelona Institute of Science and Technology (BIST) C/ Baldiri Reixac, 10-12 08028 Barcelona - Spain
contact email	masspe@irbbarcelona.org
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/2026/05/PXD067112

PRIDE project URI

• PRIDE
  1. PXD067112
     1. Label: PRIDE project
     2. Name: Endocytic Turnover of Endothelial Cell-Membrane Proteins as a Driver of Blood Brain Barrier Specialization and Dysfunction