Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The schizophrenia-associated variant in SLC39A8 alters N-glycosylation of critical proteins in the mouse brain

ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Christina Woo

LAB HEAD: Christina Woo

PROVIDER: PXD021632 | Pride | 2022-03-08

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Similar Datasets

Multilayered N-glycoproteome Profiling Reveals Highly Heterogeneous and Dysregulated Protein N-glycosylations Related to Alzheimer’s Disease

Project description:Protein N-glycosylation is ubiquitous in brain and closely related to cognition and memory. Alzheimer's disease (AD) is a multifactorial disorder that lacks clear pathogenesis and treatment. Aberrant N-glycosylation has been suggested to be involved in AD pathology. While the systematic variations of protein N-glycosylation and their roles in AD have not been thoroughly investigated due to technically challenging. Here, we applied multilayered N-glycoproteomics to quantify the global protein expression, N-glycosylation sites, N-glycans, and site-specific N-glycopeptides in AD mice brains (APP/PS1 transgenic) versus wild type. The N-glycoproteome landscape exhibited the highly complex site-specific heterogeneity in AD brains. Quantitative analyses explored the generally dysregulated N-glycosylations in AD, involving proteins such as glutamate receptors, as well as fucosylated and oligo-mannose glycans. Furthermore, functional study revealed the crucial roles of N-glycosylation on proteins and neuron cells. Our work provided a robust multilayered N-glycoproteomics workflow for AD and can be applied to widespread biological systems.

2019-11-25 | PXD015335 | Pride

Extensive heterogeneity of glycopeptides in plasma revealed by deep glycoproteomic analysis

Project description:A number of plasma glycoproteins are clinically useful as biomarkers in a variety of diseases. Although thousands of proteins are present in plasma, >95% of the plasma proteome by mass is represented by only 22 proteins. This necessitates strategies to deplete the abundant proteins and enrich other subsets of proteins. Although glycoproteins are abundant in plasma, in routine proteomic analyses, glycopeptides are not often investigated. Traditional methods such as lectin-based enrichment of glycopeptides followed by deglycosylation have helped understand the glycoproteome, but they lack any information about the attached glycans. Here, we apply size-exclusion chromatography (SEC) as a simple strategy to enrich intact glycopeptides based on their larger size which achieves broad selectivity regardless of the nature of attached glycans. Using this approach, we identified 1,317 glycopeptides belonging to 266 glycosylation sites on 154 plasma glycoproteins. The deep coverage achieved by this approach was evidenced by extensive heterogeneity that was observed. For instance, 20-100 glycopeptides were observed per protein for the top 15 glycoproteins. Overall, we found 615 novel glycopeptides of which 39 glycosylation sites (from 38 glycoproteins) are not including in protein databases such as Uniprot and GlyconnectDB. We also identified 12 novel glycopeptides containing di-sialic acid, which is a rare glycan epitope. Thus, SEC allows for efficient LC-MS/MS-based deep glycoproteomics from low amounts (~1 l) of human plasma. Overall, the SEC-based method described here is a simple, rapid and high-throughput strategy for characterization of the glycoproteome.

2021-08-18 | PXD025414 | Pride

Protein N-glycosylation is sex-related in Nilaparvata lugens adults

Project description:Nilaparvata lugens, or the brown planthopper, is one of the most notorious pest insects of cultured rice, and a model for hemimetabolous development. Recently, the N-glycome of N. lugens was explored throughout post-embryonic development and reproductive stages, which revealed differential protein N-glycosylation events between adult sexes. Identifying the proteins carrying these differential carbohydrate structures would point to the functionality of sex-dependent N-glycosylation. Furthermore, potential effects of the adult wing type on protein N-glycosylation are of interest. Here, a comprehensive investigation of the N-glycosylation sites from the adult stages of N. lugens was conducted, allowing a qualitative and quantitative comparison between sexes and wing forms at the glycopeptide level. N-glycopeptide enrichment using the N-glyco-FASP method with the high mannose/paucimannose-binding lectin Concanavalin A, or the Rhizoctonia solani agglutinin which interacts with complex N-glycans led to the identification of over 1,300 N-glycosylation sites derived from over 600 glycoproteins. Comparison of these N-glycopeptides revealed striking differences in protein N-glycosylation between sexes, while almost no differences were observed between wing types. Male- and female-specific N-glycosylation sites were identified, and some of these sex-specific N-glycosites were shown to be derived from proteins with a putative role in insect reproduction. Transcript expression experiments with complete insects and insect tissues confirmed the sex-related N-glycosylation of proteins, and expression of glycoproteins in reproductive tissues. In conclusion, this study provides original data on N-glycosylation sites of N. lugens adults, providing novel insights into planthopper’s biology and revealing that protein N-glycosylation is sex-related in this insect.

2020-01-16 | PXD013657 | Pride

Human brain glycoproteomic network alterations in Alzheimer’s disease

Project description:We performed a large-scale, site-specific N-glycoproteome profiling study of human Alzheimer’s disease (AD) and control brains using mass spectrometry–based quantitative N-glycoproteomics. The study provided a system-level view of human brain N-glycoproteins and in vivo N-glycosylation sites and identified disease signatures of altered N-glycopeptides, N-glycoproteins, and N-glycosylation site occupancy in AD. Glycoproteomic data-driven network analysis showed 13 modules of co-regulated N-glycopeptides/glycoproteins, 6 of which are associated with AD phenotypes.

2022-11-02 | PXD037229 | Pride

N-glycosylation analysis of human complement component C3 LC-MS - annotation data

Project description:The most abundant and central component, glycoprotein C3, contributes to the development of type 1 diabetes by enhancing the organ-specific autoimmune inflammatory processes. It is known that changes in glycosylation can modulate inflammatory responses and we recently showed that children at the onset of type 1 diabetes have a higher proportion of oligomannose glycans in plasma N-glycome compared to their healthy siblings. Due to fact that C3 contains two N-glycosylation sites occupied by this type of glycans, our aim was to develop a novel high-throughput and cost-effective glycoproteomic workflow for N-glycosylation analysis of human C3 to reveal the possible role of C3 glycosylation in type 1 diabetes development.

2023-03-11 | PXD035126 | Pride

N-glycosylation analysis of human complement component C3 LC-MS

2023-03-10 | PXD034083 | Pride

Probing the ovarian cancer O-glycoproteome by the Macrophage Galactose like C-type Lectin (MGL): dissecting novel patterns of immune recognition

Project description:Glycosylation, the posttranslational linking of sugar molecules to proteins, is notoriously altered during tumor transformation. More specifically in carcinomas, GalNAc-type O-glycosylation, is characterized by biosynthetically immature truncated glycans present on the cancer cell surface which profoundly impacts anti-tumor immune recognition. The tumor associated glycan pattern may thus be regarded as a biomarker of immune modulation. In Epithelial Ovarian Cancer (EOC) there is a particular lack of specific biomarkers and molecular targets to aid early diagnose and develop novel therapeutic interventions, respectively. The aim of this study was therefore to interrogate the ovarian cancer O-glycoproteome and identify tumor associated glycoproteins relevant in tumor-Dendritic Cell (DC) interactions, mediated by the MGL C-type lectin, recognizing the tumor associated Tn O-glycan. Here we present a strategy, employing a recombinant human MGL protein, to probe the ovarian cancer O-glycoproteome. This was achieved by a MGL Lectin Weak Affinity Chromatography (LWAC) approach using glycoengineered ovarian cancer cells and ovarian cancer tissues as input material. Biochemical and bioinformatics analysis allowed us to identify the glycan structure/arrangement identified by MGL and furthermore to recognize potential MGL binders located at cell membrane, as expected, but also within the intracellular compartment and the matrisome, strongly suggesting that MGL in vivo could act as sensor of cellular distress/damage and modulator of DC motility. The tumor glycoproteins binders for MGL may become relevant as potential “onco-immune” biomarkers for EOC progression and prognosis. Furthermore, these results contribute to the design of glyco-immunogens for DC-based cancer immunotherapy.

2020-10-19 | PXD017510 | Pride

Glycoproteome of Human lung cancer cell by LC-MSMS

Project description:We demonstrate the utility of lectin-magnetic nanoprobe coupled with Orbitrap HCD-CID-MS/MS for complementary glycotope-specific enrichment and site-specific glycosylation analysis of the glycoproteome. Using non-small cell lung cancer (NSCLC) cells as model, this approach allowed us to compare the glycosylation profiles of the drug resistant cell, PC9, and its resistant derivative, PC9-IR. The complementary enrichment allowed broader targeting of different glycoforms; using Byonic software, confident identification of a total of 2767 and 2290 non-redundant intact glycopeptides was achieved for PC9-IR and PC9, respectively. This also enabled glycan profiling of the onco-protein EGFR, without immunoprecipitation. Moreover, the glycan specificity afforded by the lectin@MNP allowed as to observe increased terminal and core fucosylation in EGFR from PC9-IR, which demonstrates the potential for protein glycosylation alterations in the resistant cell line. The multi-lectin nanoprobe-based affinity mass spectrometry presents a new method for large-scale glycoproteomic profiling of different sample types without prior fractionation or immunoprecipitation.

2022-02-25 | PXD010035 | Pride

Bloodstream infection N-glycoproteomics

Project description:Here we have performed targeted quantitative N-glycoproteomics from plasma samples of patients with confirmed positive blood culture together with age and sex matched febrile controls with negative blood culture reports. Three hundred and sixty eight potential N-glycopeptides were quantified by mass spectrometry and 149 were further selected for identification. Twenty four N-glycopeptides were identified with high confidence together with elucidation of the peptide sequence, N-glycosylation site, glycan composition and proposed glycan structures. these N-glycopeptides can be used as potential biomarkers of bloodstream infection.

2018-04-09 | PXD009048 | Pride

Probing endogenous peptide acceptor substrate specificities of TbSTT3A and TbSTT3B

Project description:We performed glycoproteomics on endogenous parasite glycoproteins using sequential endoglycosidase-H and peptide-N-glycosidase-F digestions, the latter in the presence of H2[18O]. This allowed us to assess the relative occupancies of native N-glycosylation sites by endoglycosidase-H resistant N-glycans originating from Man5GlcNAc2-PP-dolichol transferred by TbSTT3A, and endoglycosidase-H sensitive N-glycans originating from Man9GlcNAc2-PP-dolichol transferred by TbSTT3B.

2017-09-20 | PXD007267 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data