PXD051786

PXD051786 is an original dataset announced via ProteomeXchange.

Title	Increased expression of ATase1/NAT8B or ATase2/NAT8 in the mouse results in an autistic-like phenotype with altered dendritic branching and spine formation
Description	Neurons heavily depend on the ability of the secretory pathway to deliver correctly folded polypeptides to the periphery of the cell for the assembly, maintenance, and normal functioning of synapses. The endoplasmic reticulum (ER) acetylation machinery has emerged as a novel branch of the more general ER quality control machinery. It regulates the positive selection of correctly folded nascent glycoproteins, thus ensuring the efficiency of the secretory pathway. ER acetylation requires the activity of two ER-luminal acetylCoA:lysine acetyltransferases, ATase1/NAT8B and ATase2/NAT8. Both acetyltransferases depend on the influx of acetyl-CoA into the ER from the cytosol, which is ensued by the coordinated action of the citrate transporters, SLC25A1 and SLC13A5, and the ER acetyl-CoA transporter, AT-1. Gene duplication events affecting ATase1 and ATase2 are associated with rare disease phenotypes that include autism and intellectual disability with dysmorphism. Here, we generated mice with neuron-specific overexpression of human ATase1 or ATase2. The animals display autistic-like behaviors with altered synaptic plasticity, altered neuronal morphology, and altered synaptic structure and function. Mechanistic assessment demonstrates that widespread proteomic changes and altered dynamics of the secretory pathway underly the synaptic defects. The phenotype of ATase1 and ATase2 overexpressing mice is reminiscent of SLC25A1, SLC13A5 and AT-1 overexpressing models. Therefore, our results establish the intracellular citrate/acetyl-CoA pathway, with the ATases acting as the last output, as a metabolic pathway immediately connected to the pathogenesis of certain rare forms of ASD.
HostingRepository	PRIDE
AnnounceDate	2025-07-31
AnnouncementXML	Submission_2025-07-31_13:27:42.422.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Haiyan Lu
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-26 16:28:59	ID requested
⏵ 1	2025-07-31 13:27:42	announced

Dataset with its publication pending

submitter keyword: lysine acetylation, autism spectrum disease,ATase1, ATase2

Lingjun Li
contact affiliation	School of Pharmacy, University of Wisconsin-Madison, Madison, WI, 53705, USA
contact email	lingjun.li@wisc.edu
lab head
Haiyan Lu
contact affiliation	School of Pharmacy, University of Wisconsin-Madison
contact email	hlu244@wisc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD051786
     1. Label: PRIDE project
     2. Name: Increased expression of ATase1/NAT8B or ATase2/NAT8 in the mouse results in an autistic-like phenotype with altered dendritic branching and spine formation