PXD026624

PXD026624 is an original dataset announced via ProteomeXchange.

Title	SLC13A5/NaCT overexpression causes disrupted white matter integrity, synaptic dysfunction, and an autistic-like phenotype in the mouse
Description	Endoplasmic-reticulum (ER)-based N-lysine acetylation is a positive selection marker for properly folded glycoproteins in the early secretory pathway, serving as an important protein quality control system. Excessive N-lysine acetylation within the ER via overexpression of the acetyl-CoA transporter AT-1 results in altered glycoprotein flux through the secretory pathway, which dramatically impacts dendritic branching and spine formation causing an autistic-like phenotype in the mouse. AT-1 works in concert with SLC25A1, the citrate/malate antiporter in the mitochondria, SLC13A5, the plasma membrane sodium/citrate synporter, and ATP citrate lyase (ACLY), the cytosolic enzyme that converts citrate into acetyl-CoA, in order to maintain the cytosolic-to-ER flux of acetyl-CoA. As such, we generated the SLC13A5 neuron transgenic (nTg) mouse with the hypothesis that increasing cytosolic citrate would impact acetyl-CoA flux into the ER and recapitulate the autistic-like AT-1 nTg model. Here, we demonstrated the SLC13A5 nTg mouse exhibits autistic-like behaviors with a jumping stereotypy. The mice displayed disrupted white matter integrity and altered synaptic structure and function. Finally, analysis of both the proteome and acetylome revealed unique adaptations in the hippocampus and cortex to SLC13A5 overexpression, implicating the importance of metabolic consequences of altered cytosolic citrate/acetyl-CoA availability in the neuron. Overall, our results corroborate the mechanistic link between aberrant intracellular citrate/acetyl-CoA flux and the development of an autistic-like phenotype.
HostingRepository	PRIDE
AnnounceDate	2021-08-26
AnnouncementXML	Submission_2021-08-26_06:50:10.280.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	2021-06-10 09:04:54	ID requested
⏵ 1	2021-08-26 06:50:10	announced

Dataset with its publication pending

submitter keyword: SLC13A5;Acetyl-CoA;Mouse;LC-MS/MS

Lingjun Li
contact affiliation	PHARM/PHARMACY, UW Madison
contact email	lingjun.li@wisc.edu
lab head
Min Ma
contact affiliation	UW madison
contact email	mma58@wisc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD026624
     1. Label: PRIDE project
     2. Name: SLC13A5/NaCT overexpression causes disrupted white matter integrity, synaptic dysfunction, and an autistic-like phenotype in the mouse