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PXD059466

PXD059466 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleEndothelial SHANK3 Regulates Tight Junctions in the Neonatal Blood-Brain Barrier through β-Catenin Signaling
DescriptionAutism 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.
HostingRepositoryPRIDE
AnnounceDate2025-02-07
AnnouncementXMLSubmission_2025-02-07_07:29:37.726.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterYongeun Kim
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListbiotinylated residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-01-06 08:42:25ID requested
12025-02-07 07:29:38announced
Publication List
10.1038/S41467-025-56720-1;
Keyword List
submitter keyword: bEnd3. Cells,SHANK3, BioID2, LC-MS/MS
Contact List
Il Hwan Kim
contact affiliationDepartment of Anatomy & Neurobiology University of Tennessee Health Science Center
contact emailikim9@uthsc.edu
lab head
Yongeun Kim
contact affiliationThe University of Tennessee Health Science Center (UTHSC)
contact emailykim73@uthsc.edu
dataset submitter
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Dataset FTP location
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