PXD056477-1

PXD056477 is an original dataset announced via ProteomeXchange.

Title	Downregulation of calcium-activated potassium channels drives cortical excitability dysfunction in a model of Itgb3-associated autism
Description	Layer V pyramidal neurons, particularly pyramidal tract (PT) neurons, are essential for cortical output. Genetic studies have linked ITGB3, the gene encoding the cell-adhesion molecule β3 integrin, to autism spectrum disorder (ASD), yet its role in brain function remains poorly understood. Here, we investigate β3 integrin function in the prefrontal cortex, revealing its selective regulation of PT neuron excitability. β3 integrin modulates action potential (AP) discharge through its interaction with Ca2+-activated SK2 channels. Genetic ablation of Itgb3 reduces SK2 channel surface expression, impairing the gain, adaptation and precision of AP discharge in PT neurons. Phosphoproteomic analysis reveals altered protein kinase A (PKA)-dependent phosphorylation of Tau in Itgb3 KO mice, while PKA inhibition restores SK2 channel currents, linking phosphorylation changes to excitability defects. These findings identify a novel β3 integrin-dependent signaling pathway as a selective key modulator of PT neuron function, and provide insight into the cellular mechanisms linking dysfunction in cortical output to ASD.
HostingRepository	PRIDE
AnnounceDate	2025-10-13
AnnouncementXML	Submission_2025-10-12_16:47:42.103.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Martina Bartolucci
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-03 05:57:55	ID requested
⏵ 1	2025-10-12 16:47:43	announced

Vitale C, Jaudon F, Luj, á, n R, Bartolucci M, Celora L, Reisoli E, Ruggeri R, Petretto A, Thalhammer A, Cingolani LA, 3 integrin mouse model of autism. Brain, 148(10):3635-3651(2025) [pubmed]

10.1093/brain/awaf089;

submitter keyword: spike frequency adaptation,β3 integrin, SK2 channels, tau, layer V pyramidal neurons, PKA, afterhyperpolarization, pyramidal tract neurons, medial prefrontal cortex, intrinsic excitability

Andrea Petretto
contact affiliation	IRCCS Istituto G Gaslini
contact email	a.petretto@gmail.com
lab head
Martina Bartolucci
contact affiliation	IRCCS Gaslini
contact email	smartibartolucci@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD056477
     1. Label: PRIDE project
     2. Name: Downregulation of calcium-activated potassium channels drives cortical excitability dysfunction in a model of Itgb3-associated autism