PXD064040

PXD064040 is an original dataset announced via ProteomeXchange.

Title	Loss of Necdin causes social deficit and aberrant synaptic function through destabilization of SynGAP
Description	The Ras GTPase-activating protein SynGAP interacts with PSD95 to regulate synaptic morphology and function at the postsynaptic density in neurons. Haploinsufficiency of SYNGAP1 has been linked to autism spectrum disorders (ASD) and intellectual disability (ID). While transcriptional and translational regulation of SYNGAP1 has been extensively explored, the mechanisms governing its protein homeostasis remain largely elusive. In this study, we discovered that Necdin, a protein linked to Prader-Willi syndrome (PWS), interacts with SynGAP and regulates its stability through the SGT1-HSP90 chaperone machinery; notably, loss of Necdin results in decreased SynGAP protein levels in mice. Necdin-deficient mice exhibited impaired sociability, accompanied by an increased number of dendritic spines and a higher proportion of mature spines in pyramidal neurons of the medial prefrontal cortex (mPFC). Electrophysiological recordings revealed elevated frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) and reduced amplitude of miniature inhibitory postsynaptic currents (mIPSCs) in these neurons. Targeted viral overexpression of Syngap1 in the mPFC of Necdin-deficient mice rescued the deficits in sociability, synaptic function, and dendritic spine morphology. Collectively, our findings reveal Necdin as a key regulator of SynGAP protein homeostasis and highlight the contribution of post-translational regulation in the pathogenesis of ASD.
HostingRepository	iProX
AnnounceDate	2025-05-17
AnnouncementXML	Submission_2025-05-18_23:11:19.191.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xiangyu Li
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-18 23:11:03	ID requested
⏵ 1	2025-05-18 23:11:19	announced

Dataset with its publication pending

submitter keyword: Necdin, SynGAP, Autism, Synapse

Jiada Li
contact affiliation	Central South University
contact email	lijiada@csu.edu.cn
lab head
Xiangyu Li
contact affiliation	Central South University
contact email	lixiangyu@sklmg.edu.cn
dataset submitter

iProX dataset URI