PXD021632

PXD021632 is an original dataset announced via ProteomeXchange.

Title	The schizophrenia-associated variant in SLC39A8 alters N-glycosylation of critical proteins in the mouse brain
Description	A missense mutation (A391T) in the manganese transporter SLC39A8 is strongly associated with schizophrenia through GWAS, though the molecular connection to the brain remains hypothetical. Human carriers of A391T have reduced serum manganese, altered plasma glycosylation, and brain MRI changes consistent with altered metal transport. Here, using a mouse knock-in model homozygous for A391T, we show that the schizophrenia-associated variant changes protein glycosylation in the brain. N-linked glycosylation was most significantly impaired, with effects differing between regions. RNAseq analysis showed negligible variation, consistent with changes in the activity of glycosylation enzymes rather than gene expression. Finally, one third of all detected glycoproteins were differentially N-glycosylated in the cortex, including members of several pathways previously implicated in schizophrenia such as cell adhesion molecules and neurotransmitter receptors. These findings provide a mechanistic link between a risk allele and biochemical changes in the brain, furthering our molecular understanding of the pathophysiology of schizophrenia.
HostingRepository	PRIDE
AnnounceDate	2022-03-08
AnnouncementXML	Submission_2022-03-08_07:26:38.688.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD021632
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Christina Woo
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	deamidated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-22 09:06:58	ID requested
⏵ 1	2022-03-08 07:26:39	announced

Dataset with its publication pending

submitter keyword: Schizophrenia

SLC39A8

mouse

N-linked glycosylation

Christina Woo
contact affiliation	DEPARTMENT of CHEMISTRY & CHEMICAL BIOLOGY HARVARD UNIVERSITY
contact email	cwoo@chemistry.harvard.edu
lab head
Christina Woo
contact affiliation	Harvard University
contact email	cwoo@chemistry.harvard.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/2022/03/PXD021632

PRIDE project URI

• PRIDE
  1. PXD021632
     1. Label: PRIDE project
     2. Name: The schizophrenia-associated variant in SLC39A8 alters N-glycosylation of critical proteins in the mouse brain