Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Chondrodysplasia-inducing COL2A1 p.Gly1170Ser causes an ER storage defect without associated unfolded protein response in a human cartilage model

ABSTRACT: 10-plex TMT dataset generated by immunoprecipitation of epitope-tagged COL2A1 constructs along with DSP-crosslinked interactors. This experiment allows for quantitative comparison of wild-type and Gly1170Ser COL2A1 interactomes in HT-1080 cells transiently transfected with COL2A1 under a constitutive promoter. Negative control samples are untransfected HT-1080 cells, used to identify high-confidence collagen-II interactors from non-specific binders.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Matthew Shoulders

PROVIDER: MSV000093517 | MassIVE | Tue Nov 28 05:55:00 GMT 2023

SECONDARY ACCESSION(S): PXD047329

REPOSITORIES: MassIVE

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Chondrodysplasia-inducing COL2A1 p.Gly1170Ser causes an ER storage defect without associated unfolded protein response in chondronoids

Project description:Collagenopathies are a group of clinically diverse disorders caused by defects in collagen folding and secretion. For example, mutations in the gene encoding collagen type-II (COL2A1), the primary collagen in cartilage, can lead to chondrodysplasias of various severities. One example is the Gly1170Ser substitution in procollagen-II, which causes precocious osteoarthritis and Legg-Calvé-Perthes disease. Here, we develop and characterize a novel induced pluripotent stem cell-based cartilage model of this disease, including both hetero- and homozygous genotypes. Biochemical characterization reveals that Gly1170Ser procollagen-II is notably slow to fold and secrete. Instead, procollagen-II accumulates intracellularly, consistent with an endoplasmic reticulum (ER) storage disorder. Intriguingly, though perhaps due to the pathologic substitution occurring within a triple-helical domain that lacks hydrophobic character, this intra-ER protein accumulation is not recognized by cellular stress responses, such as the unfolded protein response. Interactome studies showed that Gly1170Ser procollagen-II interacts to a greater extent with certain ER chaperones and modifying enzymes, consistent with its slow folding. These findings provide mechanistic elucidation into the etiology of this disease. Moreover, the expandable cartilage model developed here provides a valuable platform to rapidly screen and develop therapeutic strategies that can restore procollagen folding and secretion in this collagenopathy and others.

2024-07-02 | GSE244375 | GEO

Postnatal Deletion of Fat Storage-inducing Transmembrane Protein 2 (FIT2/FITM2) Causes Lethal Enteropathy.

Project description:Lipid droplets (LDs) are phylogenetically conserved cytoplasmic organelles that store neutral lipids within a phospholipid monolayer. LDs compartmentalize lipids and may help to prevent cellular damage caused by their excess or bioactive forms. FIT2 is a ubiquitously expressed transmembrane endoplasmic reticulum (ER) membrane protein that has previously been implicated in LD formation in mammalian cells and tissue. Recent data indicate that FIT2 plays an essential role in fat storage in an in vivo constitutive adipose FIT2 knock-out mouse model, but the physiological effects of postnatal whole body FIT2 depletion have never been studied. Here, we show that tamoxifen-induced FIT2 deletion using a whole body ROSA26CreER(T2)-driven FIT2 knock-out (iF2KO) mouse model leads to lethal intestinal pathology, including villus blunting and death of intestinal crypts, and loss of lipid absorption. iF2KO mice lose weight and die within 2 weeks after the first tamoxifen dose. At the cellular level, LDs failed to form in iF2KO enterocytes after acute oil challenge and instead accumulated within the ER. Intestinal bile acid transporters were transcriptionally dysregulated in iF2KO mice, leading to the buildup of bile acids within enterocytes. These data support the conclusion that FIT2 plays an essential role in regulating intestinal health and survival postnatally.

| S-EPMC4646211 | biostudies-other

Chondrodysplasia-inducing COL2A1 p.Gly1170Ser causes an ER storage defect without associated unfolded protein response in chondronoids

Project description:Chondrodysplasia-inducing COL2A1 p.Gly1170Ser causes an ER storage defect without associated unfolded protein response in chondronoids

| PRJNA1022488 | ENA

A multimodal assay identifies optimized binders for a bicistronic CAR against GPC2 OR CD276 to overcome heterogeneity in Neuroblastoma

Project description:Neuroblastoma (NB) is the most common extra-cranial solid tumor in children and remains deadly in patients with high-risk disease. Single chimeric antigen receptor T-cell therapies (CAR-T) for solid tumor have shown poor efficacy in clinical trials due, in part, to T cell exhaustion and uneven expression of target antigens in tumors. Here, we attempted to target Glypican-2(GPC2) and CD276(B7-H3), both highly but heterogeneously expressed on NB cell surface, to overcome these challenges in single CAR T- therapies. First, to identify optimal binders for CAR T- cell targeting each antigen, we made individual CAR constructs using multiple binders against these antigens and utilized a multimodal approach including simultaneous protein and transcriptome measurement at single cell level to characterize each individual CAR T- cell in a pooled strategy. Combined with cell expansion and cytotoxicity assays, we identified the most effective CAR construct for each target.

2022-03-18 | GSE181437 | GEO

Candidate target proteins of NbERD15La in Nicotiana benthaminan

Project description:To identify the potential host interactors of NbERD15La, we transiently expressed NbERD15La in N. benthamiana and screened for protein interactors using co-immunoprecipitation (Co-IP) followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).

2023-11-08 | PXD046771 |

Advanced Strategies for Articular Cartilage Defect Repair.

Project description:Articular cartilage is a unique tissue owing to its ability to withstand repetitive compressive stress throughout an individual's lifetime. However, its major limitation is the inability to heal even the most minor injuries. There still remains an inherent lack of strategies that stimulate hyaline-like articular cartilage growth with appropriate functional properties. Recent scientific advances in tissue engineering have made significant steps towards development of constructs for articular cartilage repair. In particular, research has shown the potential of biomaterial physico-chemical properties significantly influencing the proliferation, differentiation and matrix deposition by progenitor cells. Accordingly, this highlights the potential of using such properties to direct the lineage towards which such cells follow. Moreover, the use of soluble growth factors to enhance the bioactivity and regenerative capacity of biomaterials has recently been adopted by researchers in the field of tissue engineering. In addition, gene therapy is a growing area that has found noteworthy use in tissue engineering partly due to the potential to overcome some drawbacks associated with current growth factor delivery systems. In this context, such advanced strategies in biomaterial science, cell-based and growth factor-based therapies that have been employed in the restoration and repair of damaged articular cartilage will be the focus of this review article.

| S-EPMC5452095 | biostudies-other

Proteome analysis of affinity-purified protein co-precipitates

Project description:Proteome analysis of affinity-purified materials prepared from chromatin fractions of HEK293T cells expressing various constructs. HEK293T cells transiently expressing various constructs were subjected to fanChIP (fractionation-assisted chromatin immunoprecipitation) method described in our previous paper (Okuda et al. 2014 Nucleic Acids Research 42;7 p4241-4256).

2021-06-15 | PXD019783 | JPOST Repository

Structural insights into triglyceride storage mediated by fat storage-inducing transmembrane (FIT) protein 2.

Project description:Fat storage-Inducing Transmembrane proteins 1 & 2 (FIT1/FITM1 and FIT2/FITM2) belong to a unique family of evolutionarily conserved proteins localized to the endoplasmic reticulum that are involved in triglyceride lipid droplet formation. FIT proteins have been shown to mediate the partitioning of cellular triglyceride into lipid droplets, but not triglyceride biosynthesis. FIT proteins do not share primary sequence homology with known proteins and no structural information is available to inform on the mechanism by which FIT proteins function. Here, we present the experimentally-solved topological models for FIT1 and FIT2 using N-glycosylation site mapping and indirect immunofluorescence techniques. These methods indicate that both proteins have six-transmembrane-domains with both N- and C-termini localized to the cytosol. Utilizing this model for structure-function analysis, we identified and characterized a gain-of-function mutant of FIT2 (FLL(157-9)AAA) in transmembrane domain 4 that markedly augmented the total number and mean size of lipid droplets. Using limited-trypsin proteolysis we determined that the FLL(157-9)AAA mutant has enhanced trypsin cleavage at K86 relative to wild-type FIT2, indicating a conformational change. Taken together, these studies indicate that FIT2 is a 6 transmembrane domain-containing protein whose conformation likely regulates its activity in mediating lipid droplet formation.

| S-EPMC2875400 | biostudies-literature

Treatment of glenoid chondral defect using micronized allogeneic cartilage matrix implantation.

Project description:Focal chondral lesions of the glenohumeral joint, though less common than chondral defects in the knee or ankle, can be a significant source of pain in an active population. For patients in whom nonsurgical management fails, promising results have been reported after arthroscopic microfracture surgery to treat such lesions. However, microfracture leads to growth of fibrocartilage tissue and is biomechanically less durable than native hyaline cartilage. Recently, augmentation of the microfractured defect with micronized allogeneic cartilage and platelet-rich plasma has been described to restore hyaline-like cartilage and potentially protect the subchondral bone from postsurgical fracture biology within the base of the defect. We present a simple arthroscopic technique of implanting dehydrated, micronized allogeneic cartilage scaffold to treat an isolated chondral lesion of the glenoid.

| S-EPMC4175152 | biostudies-literature

Engraftment of allogeneic iPS cell-derived cartilage organoid in a primate model of articular cartilage defect

Project description:Induced pluripotent stem cells (iPSCs) are a promising resource for allogeneic cartilage transplantation to treat articular cartilage defects that do not heal spontaneously and often progress to debilitating conditions, such as osteoarthritis. However, to the best of our knowledge, allogeneic cartilage transplantation into primate models has never been assessed. Here, we show that allogeneic iPSC-derived cartilage organoids survive and integrate as well as function as articular cartilage in a primate model of chondral defects in the knee joints. Histological analysis revealed that allogeneic iPSC-derived cartilage organoids in chondral defects elicited no immune reaction and directly contributed to the tissue repair for at least four months. iPSC-derived cartilage organoids integrated with the host native articular cartilage and prevented degeneration of the surrounding cartilage. Single-cell RNA-sequence analysis indicated that iPSC-derived cartilage organoids differentiated after transplantation, acquiring expression of PRG4 that is crucial for joint lubrication. Pathway analysis suggested the involvement of SIK3 inactivation, verified through molecular experiments. Our study outcomes suggest that allogeneic transplantation of iPSC-derived cartilage organoids may be clinically applicable for the treatment of patients with chondral defects of the articular cartilage.

2023-01-23 | GSE206120 | GEO

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