Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Myelin basic protein is an RNA chaperone in microglial nuclear retro-transport

ABSTRACT: CNS oligodendrocytes generate myelin, an RNA-containing proteolipid substance that enhances axonal transmission. In multiple sclerosis (MS), myelin debris is phagocytosed by microglia (MG), and prior studies have detected myelin-derived mRNA in MG nuclei, suggesting a retrograde transport pathway. We report myelin basic protein (MBP) is a nucleic acid–binding and trafficking protein. We found that retro-transport of myelin RNA into the MG nucleus was phagocytosis and importin-dependent. Transcriptomic and proteomic analyses of MG nuclei revealed enrichment of myelin mRNAs and proteins, with MBP singularly detected in soluble and chromatin-associated fractions. MBP bound mRNA with high affinity (Kd ≈ 0.30 nM) and was sufficient to facilitate MG RNA nuclear import in vitro and in vivo. Functionally, MBP mediated the delivery of small interfering RNAs for targeted knockdown of toll-like receptor 4. These findings indicate MBP as an RNA-binding protein capable of MG nuclear import, providing insight into neuroinflammatory pathology of MS.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE330818 | GEO | 2026/06/20

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Amyloid-β increases MBP and MOBP translation in oligodendrocytes through dysregulation of hnRNP A2-dependent RNA dynamics

Project description:Oligodendrocyte dysfunction, myelin degeneration, and white matter structural alterations are critical events in Alzheimer's disease (AD) that contribute to cognitive decline. A key hallmark of AD, Aβ oligomers, disrupt oligodendrocyte and myelin homeostasis, but a comprehensive global analysis of the mechanisms involved is lacking. Here, transcriptomic profiling of Aβ-exposed oligodendrocytes revealed widespread gene expression changes, particularly affecting pathways related to RNA localisation. Among the genes identified, we focused on Hnrnpa2/b1, the gene encoding the hnRNP A2 protein, which is essential for RNA transport and translation of myelin proteins. We confirmed aberrant upregulation of hnRNP A2 in hippocampal oligodendrocytes from post-mortem human brains of early-stage AD patients, Aβ-injected mouse hippocampi and Aβ-treated disrupting cells in vitro. RIP-seq analysis of the hnRNP A2 interactome revealed attenuated interactions with Hnrnpk and Hnrnpa2/b1, while interactions with Mbp and Mobp were enriched, suggesting changes in RNA metabolism of molecules associated with mRNA transport of myelin proteins. Aβ increased the total number and dynamics of mRNA-containing granules, facilitating local translation of the myelin proteins MBP and MOBP and attenuating Ca2+ signalling. These findings suggest that Aβ oligomers disrupt RNA metabolism mechanisms crucial for oligodendrocyte myelination through dysregulation of hnRNP A2 and myelin protein levels, potentially affecting oligodendroglia Ca2+ homeostasis.

2025-01-02 | GSE263799 | GEO

White matter integrity requires continuous myelin synthesis at the inner tongue

Project description:Myelin, the electrically insulating axonal sheath, is composed of lipids and proteins with exceptionally long lifetime. Using 3D electron microscopy, mass spectrometry imaging, and quantitative proteome analysis, we addressed the question how myelin function is affected by myelin turnover. We studied the integrity of myelinated tracts after experimentally preventing the formation of new myelin in the CNS of adult mice by an inducible myelin basic protein (Mbp) null allele. Recombined oligodendrocytes continued to express myelin genes, but failed to establish MBP-dependent compaction of myelin sheaths. Abundance changes of myelin proteins upon Mbp ablation were analyzed in whole optic nerve lysates at different time points and compared with shiverer mice. This naturally occurring mutant is inable to developmentally form compact myelin due to the lack of MBP and served as proxy for the demyelination endpoint. Label-free protein quantification using an ion mobility-enhanced data-independent acquisition (DIA) workflow with alternating low and elevated energy (referred to as UDMS^E) revealed that numerous myelin proteins are reduced in abundance, while microglia and astrocyte markers were increased, indicative of neuropathology. Taken together, we observed an axonal pathology with about 50% myelin loss after 20 weeks and concluded that functional axon-myelin units require the continuous incorporation of new myelin membranes.

2022-01-14 | PXD025180 | Pride

Gene Expression Profiles of Lymphocytes Obtained from Mice treated with Glatimer Acetate and ither Glatiramatoids

Project description:Glatiramer acetate (GA; Copaxone), is a complex mixture of synthetic polypeptides approved for treatment of multiple sclerosis (MS). GA is an altered peptide ligand (APL) of myelin basic protein (MBP), an encephalitic autoantigen implicated in MS. GA induces GA-reactive T cells, which upregulate expression of anti-inflammatory and neurotrophic substances in the CNS. The antigenic sequences in glatiramoids cannot be completely characterized; nevertheless, differences among them can cause toxicity. We conducted microarray analyses to determine whether gene expression by GA-reactive lymphocytes from mouse spleens could differentiate GA from other glatiramoids. Expression of 135 genes was unique to cells reactivated by GA vs by intentionally altered GA and other glatiramoids. Significantly (p<0.01) altered expression of 207 genes was observed by cells reactivated by GA vs purported generic GA. Some APLs of MBP have caused serious adverse effects in MS patients. The influence of altered gene expression on glatiramoid safety warrants further investigation.

2013-08-01 | GSE40566 | GEO

Proteome analysis of the MO3.13 cell line from human oligodendrocytes

Project description:MO3.13 is an immortal human-human hybrid cell line that express phenotypic characteristics of primary oligodendrocytes. It was created by fusing a 6-thioguanine-resistant mutant of the human rhabdomyosarcoma RD (cancer of skeletal muscle) with adult human oligodendrocytes by a lectin-enhanced polyethylene glycol procedure. In contrast to the tumor parent, MO3.13 expressed surface immunoreactivity for galactosyl cerebroside(GS) and intracellular immunoreactivity for myelin basic protein (MBP), proteolipid protein (PLP), and glial fibrillary acidic protein (GFAP). MO3.13 also exhibit the markers of immature oligodendrocytes GalC (galactosylceramidase) and CNPase. Upon differentiation, the MO3.13 cells have been also shown to express the MBP and MOG markers. Data analysis: Each MS raw file was processed using ProteoWizard for the generation of a MGF file. These were processed in SearchGUI, which runs the search engines Open Mass Spectrometry Search Algorithm (OMSSA) and X!Tandem against the UniProt human protein database (release 2013_08, 20,266 sequences). Search parameters were: peptide and fragment ion mass accuracy 10 ppm and 0.5 Da, respectively; protein and peptide FDRs 1%; two miss cleavages; trypsin as enzyme; fixed modifications: cysteine carbamidomethylation; variable modifications: methionine oxidation. In order to generate one single proteome dataset of MO3.13, resulting data was processed in PeptideShaker.

2013-10-09 | PXD000263 | Pride

Immunodominant myelin basic protein fragments induce mechanical hypersensitivity.

Project description:An insulating myelin sheath ensures saltatory conduction of mechanosensory A afferents. Myelin damage results in the electrical instability of A fibers and the ability to generate pain in response to light touch/pressure (mechanical allodynia). We have hypothesized and then established that the release of T cell epitopes of myelin basic protein (MBP) enables nociceptive circuitry in myelinated fibers. Thus, mass spectrometry analysis of the rat sciatic nerve proteome followed by bioinformatics examination of the datasets revealed a loss of MBP and activation of T-helper cell signaling in the nerves undergoing chronic constriction injury (CCI). Matrix metalloproteinase-9 (MMP-9) proteolysis resulted in the MBP digest peptides, including the MBP84-104 and MBP68-86 regions, which exhibit prominent immunogenic epitopes. Myelin-forming Schwann cells and paranodal areas accumulated MHCII, MMP-9 and the degraded MBP at the sciatic nerve injury site. Administration of the immunodominant MBP84-104 and MBP68-86 peptides but not of the control peptides in a naïve rat sciatic nerve produced robust mechanical allodynia. Allodynia was accompanied by the T cell infiltration and an increase in MHCII, IL-17A and TNF- levels at the nerve injection site and the segmental ganglia. The pro-nociceptive activity of the synthetic MBP84-104 diminished in athymic nude rats lacking T cells. SB-3CT, an antagonist of MMP-9, inhibited mechanical allodynia, neuroinflammation and spinal sensitization after CCI. Collectively, our novel data implicate, for the first time, MMP-mediated cleavage of MBP and the resulting MBP digest fragments as a major cause of neuropathic pain. Gene extression profiling of total RNAs extracted from rat sciatic nerves, dorsal root ganglion and spinal cords after MBP84-104 peptide injection

2012-03-03 | E-GEOD-34868 | biostudies-arrayexpress

SILAC-Tp (12 importins)

Project description:Importin-beta family proteins are nucleocytoplasmic transport receptors (NTRs), and they transport most nuclear proteins as their cargoes into and out of the nuclei. Human cells have 20 species of importin-beta family NTRs, of which 10 (importin-beta, transportin-1, -2, -SR, importin-4, -5, -7, -8, -9, and -11) are nuclear import receptors and 2 (importin-13, and exportin-4) are bi-directional receptors. Here, we identified the import cargo proteins of these 12 NTRs by a method called SILAC-Tp, which employs stable isotope labeling with amino acids in cell culture (SILAC), an in vitro reconstituted transport system, and LC-MS/MS.

2017-03-30 | MSV000080815 | MassIVE

Comprehensive atlas of the myelin basic protein interaction landscape

Project description:Intrinsically disorder myelin basic protein (MBP) is one of the key autoantigens in autoimmune neurodegeneration and multiple sclerosis particularly. MBP is highly positively charged and lacks distinct structure in solution and therefore its intracellular part-ners are still mostly enigmatic. Here we used combination of formaldehyde-induced cross-linking followed by immunoprecipitation and Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) to elucidate the interaction network of MBP in mammalian cells and provide the list of potential MBP interacting proteins. Our data suggest that the largest group of MBP-interacting proteins belongs to cellular proteins involved in the protein translation machinery, as well as in the spatial and temporal regulation of translation. MBP interacts with core ribosomal proteins, RNA helicase Ddx28 and RNA-binding proteins STAU1, ADAR-1 and hnRNP A0, which are involved in various stages of RNA biogenesis and processing, including specific maintaining MBP-coding mRNA. Among MBP partners we identified CTNND1, which has previously been shown to be necessary for myelinating Schwann cells, for cell-cell interactions and the formation of a normal myelin sheath. MBP binds proteins MAGEB2/D2 associated with neurotrophin receptor p75NTR, involved in pathways that promote neuronal survival and neuronal death. Finally, we observed that MBP interacts with RNF40 – a component of heterotetrameric Rnf40/Rnf20 E3 ligase complex, recruited by Egr2, which is the central transcriptional regulator of peripheral myelination. Concluding, our data suggest that MBP may be more actively involved in myelination not only as a main building block but also as a regulating element.

2022-02-16 | PXD028685 | Pride

SILAC-Tp (12 importins) - Extensive cargo identification reveals distinct biological roles of the 12 importin pathways

2017-01-20 | PXD004655 | Pride

Transcription profiling of mouse MBP Ac 11-11 activated purified CD4+ T cells

Project description:Local catabolism of the amino acid tryptophan (Trp) by indoleamine-2,3-dioxygenase (IDO) is considered an important mechanism of regulating T cell immunity. We show that IDO transcription was increased upon stimulation of myelin-specific T cells with tolerogenic altered self-peptides. Catabolites of Trp suppressed proliferation of myelin-specific T cells and inhibited production of proinflammatory TH1 cytokines. N-(3,4,-dimethoxycinnamoyl) anthranilic acid (3,4-DAA), an orally active synthetic derivative of the Trp metabolite anthranilic acid, reversed paralysis in mice with experimental autoimmune encephalomyelitis, a model of multiple sclerosis (MS). Trp catabolites and their derivatives offer a new strategy for treating TH1-mediated autoimmune diseases, such as MS. 4Y vd 1-11 comparison files are available as supplementary files. Experiment Overall Design: Double stranded cDNA was generated from total RNA extracted from MBP Ac 11-11 activated purified CD4+ T cells. Biotinylated cRNA was manufactured by in vitro transcription and hybridized to the Affymetrix genechip murine Mu11k set according to the manufacturer's protocols. Results were calculated as the ratio of mean average differences for each gene in 4Y versus Ac1-11 stimulated samples.

2008-06-12 | E-GEOD-3401 | biostudies-arrayexpress

 Autoreactive T Cells Recognize Unique MBP Peptides Naturally Presented by EBV-Infected B Cells and Multiple Sclerosis Brain Tissue

Project description:Epstein-Barr virus (EBV) is involved in causing and probably also perpetuating multiple sclerosis (MS). Among several mechanisms, how EBV may contribute, are transcriptome alterations including changes of antigen processing and preferential presentation of both viral and self-antigens. Here, we found that EBV reprograms the transcriptome and immunopeptidome presented on the MS-associated HLA-DR15 molecules of infected B cells. Identical myelin basic protein (MBP) peptides were found to be presented on both EBV-infected B cells and MS brain tissue but not primary B cells and thymic tissue. Peripheral memory and cerebrospinal fluid (CSF)-derived CD4+ T cells of HLA-DR15+ MS patients responded to MBP peptides, MBP(78-90) and/or MBP(83-90), and T cell clones raised with these peptides recognized all MBP peptides ending at amino acid MBP90 in MS brain tissues. Our study provides a new mechanistic link how the environmental and genetic risk factors, EBV infection and HLA-DR15 haplotype, may contribute jointly to MS.

2026-03-11 | PXD068488 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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