PXD059466

PXD059466 is an original dataset announced via ProteomeXchange.

Title	Endothelial SHANK3 Regulates Tight Junctions in the Neonatal Blood-Brain Barrier through β-Catenin Signaling
Description	Autism spectrum disorder (ASD) is a neurodevelopmental condition caused by a combination of genetic and environmental factors. The blood-brain barrier (BBB) plays a key role in regulating environmental influences on the brain, yet its contributions to ASD remain unclear. We report that endothelium-specific SHANK3 (eSHANK3) is expressed in brain endothelial cells (BECs) that form the BBB. Our analysis of eSHANK3 interactions in BECs shows significant enrichment of proteins involved in membrane and cell junction functions. We found that eSHANK3 maintains tight junction (TJ) integrity, which is essential for BBB function. Loss of Shank3 disrupts TJs, increasing paracellular passage through the endothelium. In vivo, eShank3 knockout (KO) mice show BBB hyperpermeability, reduced neuronal excitability, and impaired ultrasonic communication. Although BBB permeability is restored in adulthood, the mutant mice continue to have reduced neuronal excitability and impaired sociability. Further analysis reveals that neonatal BBB hyperpermeability is due to β-Catenin imbalance caused by eShank3-KO. Restoring β-Catenin signaling rescues neuronal and social behavior deficits. These findings uncover a new pathogenic mechanism linked to Shank3 in ASD and suggest that neonatal BECs in the BBB could be a potential therapeutic target for ASD.
HostingRepository	PRIDE
AnnounceDate	2025-02-07
AnnouncementXML	Submission_2025-02-07_07:29:37.726.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yongeun Kim
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	biotinylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-06 08:42:25	ID requested
⏵ 1	2025-02-07 07:29:38	announced

10.1038/S41467-025-56720-1;

submitter keyword: bEnd3. Cells,SHANK3, BioID2, LC-MS/MS

Il Hwan Kim
contact affiliation	Department of Anatomy & Neurobiology University of Tennessee Health Science Center
contact email	ikim9@uthsc.edu
lab head
Yongeun Kim
contact affiliation	The University of Tennessee Health Science Center (UTHSC)
contact email	ykim73@uthsc.edu
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/2025/02/PXD059466

PRIDE project URI

• PRIDE
  1. PXD059466
     1. Label: PRIDE project
     2. Name: Endothelial SHANK3 Regulates Tight Junctions in the Neonatal Blood-Brain Barrier through β-Catenin Signaling