PXD059466 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2025-01-06 08:42:25 | ID requested | |
⏵ 1 | 2025-02-07 07:29:38 | announced | |
Publication List
Keyword List
submitter keyword: bEnd3. Cells,SHANK3, BioID2, LC-MS/MS |
Contact List
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 | |
Full Dataset Link List
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 |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD059466
- Label: PRIDE project
- Name: Endothelial SHANK3 Regulates Tight Junctions in the Neonatal Blood-Brain Barrier through β-Catenin Signaling