PXD025415

PXD025415 is an original dataset announced via ProteomeXchange.

Title	Increased expression of SLC25A1/CIC in the mouse results in an autistic-like phenotype with altered white matter microstructure and neuron morphology
Description	Ne-lysine acetylation within the lumen of the endoplasmic reticulum (ER) is a recently characterized protein quality control system that positively selects properly folded glycoproteins in the early secretory pathway. Overexpression of the ER acetyl-CoA transporter AT-1 in mouse forebrain neurons results in increased dendritic branching, spine formation, and an autistic-like phenotype that is attributed to altered glycoprotein flux through the secretory pathway. AT-1 overexpressing neurons maintain the cytosolic pool of acetyl-CoA by upregulation of SLC25A1, the mitochondrial citrate/malate antiporter, and ATP citrate lyase (ACLY), which converts cytosolic citrate into acetyl-CoA. All three genes have been associated with autism spectrum disorder (ASD), suggesting that aberrant cytosolic to ER flux of acetyl-CoA can be a mechanistic driver for the development of ASD. We therefore generated a SLC25A1 neuron transgenic (nTg) mouse, which displayed autistic-like behaviors with a jumping stereotypy. The mice exhibited increased steady-state levels of citrate and acetyl-CoA, disrupted white matter integrity with activated microglia, and altered synaptic plasticity and morphology. Finally, acetylomic and proteomic analysis revealed differential adaptations in the hippocampus and cortex. Overall, our study reinforces the connection between aberrant cytosol-to-ER flux of acetyl-CoA flux and the development of an autistic-like phenotype.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:52:54.142.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Min Ma
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-15 01:42:28	ID requested
1	2022-02-25 16:40:58	announced
⏵ 2	2023-11-14 08:52:54	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: Dileu labeing,acetyl-CoA,autism spectrum disorder, LC-MS/MS

Lingjun Li
contact affiliation	School of pharmacy, University of Wisconsin-madison
contact email	lingjun.li@wisc.edu
lab head
Min Ma
contact affiliation	UW madison
contact email	mma58@wisc.edu
dataset submitter

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/2022/02/PXD025415

PRIDE project URI

• PRIDE
  1. PXD025415
     1. Label: PRIDE project
     2. Name: Increased expression of SLC25A1/CIC in the mouse results in an autistic-like phenotype with altered white matter microstructure and neuron morphology