PXD021632 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-09-22 09:06:58 | ID requested | |
⏵ 1 | 2022-03-08 07:26:39 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Schizophrenia |
SLC39A8 |
mouse |
N-linked glycosylation |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD021632
- Label: PRIDE project
- Name: The schizophrenia-associated variant in SLC39A8 alters N-glycosylation of critical proteins in the mouse brain