Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA113249 | ENA |
REPOSITORIES: ENA
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Project description:Protein disulfide isomerases (PDIs) aid protein folding and assembly by catalyzing formation and shuffling of cysteine disulfide bonds in the endoplasmic reticulum (ER). Many members of the PDI family are expressed in mammals but the roles of specific PDIs in vivo are poorly understood. A recent homology-based search for additional PDI family members identified anterior gradient homolog 2 (AGR2), a protein originally presumed to be secreted by intestinal epithelial cells, but the function of AGR2 has been obscure. Here we show that AGR2 is expressed in the ER of secretory cells and is essential for in vivo production of intestinal mucin, a large cysteine-rich glycoprotein that forms the protective mucus gel lining the intestine. A cysteine residue within the AGR2 thioredoxin-like domain forms mixed disulfide bonds with MUC2, consistent with a direct role for AGR2 in mucin processing. Despite a complete absence of intestinal mucin, mice lacking AGR2 appeared healthy but were highly susceptible to dextran sodium sulfate-induced experimental colitis, indicating a critical role for AGR2 in protection from environmental insults. We conclude that AGR2 is a unique member of the PDI family that has a specialized and non-redundant role in intestinal mucus production. Keywords: small intestine and colon gene expression profiles for Agr2-/- and littermate control mice
2009-05-15 | GSE12503 | GEO
Project description:Protein disulfide isomerases (PDIs) aid protein folding and assembly by catalyzing formation and shuffling of cysteine disulfide bonds in the endoplasmic reticulum (ER). Many members of the PDI family are expressed in mammals but the roles of specific PDIs in vivo are poorly understood. A recent homology-based search for additional PDI family members identified anterior gradient homolog 2 (AGR2), a protein originally presumed to be secreted by intestinal epithelial cells, but the function of AGR2 has been obscure. Here we show that AGR2 is expressed in the ER of secretory cells and is essential for in vivo production of intestinal mucin, a large cysteine-rich glycoprotein that forms the protective mucus gel lining the intestine. A cysteine residue within the AGR2 thioredoxin-like domain forms mixed disulfide bonds with MUC2, consistent with a direct role for AGR2 in mucin processing. Despite a complete absence of intestinal mucin, mice lacking AGR2 appeared healthy but were highly susceptible to dextran sodium sulfate-induced experimental colitis, indicating a critical role for AGR2 in protection from environmental insults. We conclude that AGR2 is a unique member of the PDI family that has a specialized and non-redundant role in intestinal mucus production. Keywords: small intestine and colon gene expression profiles for Agr2-/- and littermate control mice DNA miocroarrays were used to analyze small intenstine and colon mRNA expression of AGR2 KO and littermate control mice. The experiment incorporated a 1 color design and used Agilent arrays that contained roughly 44,00 60mer probes that provide complete coverage of the mouse genome. 12 arrays were hybridized and represent 8 small intestine samples ( 4 each KO and WT) and 4 colon samples (2 each KO and WT)
2010-05-19 | E-GEOD-12503 | biostudies-arrayexpress
Project description:The de novo Autism Spectrum Disorder RELN R2290C Mutation Reduces Reelin Secretion and Increases Protein Disulfide Isomerase Expression
| PRJNA381193 | ENA
Project description:This study tested the hypothesis that a medicinal plant, Vasaka, typically consumed as a tea to treat respiratory malaise, could protect airway epithelial cells (AECs) from wood smoke particle-induced damage and prevent pathological mucus expression. Wood/biomass smoke is a common pneumotoxic air pollutant that activates transient receptor potential ankyrin 1 (TRPA1) and causes endoplasmic reticulum (ER) stress and AEC damage. This stimulates epidermal growth factor receptor and mucin 5AC (MUC5AC) production by AECs. Mucus normally protects the airways, but excessive MUC5AC production can obstruct airflow and cause respiratory distress. Vasaka tea pre- and co-treatment dose-dependently inhibited MUC5AC mRNA induction in cells treated with wood smoke particles. This correlated with TRPA1 inhibition, an attenuation of ER stress, and AEC damage/death, among other effects. Induction of mRNA for Anterior Gradient 2 (AGR2), an ER chaperone/disulfide isomerase required for MUC5AC production, and TRP vanilloid-3 (TRPV3), a gene that suppresses ER stress and wood smoke particle-induced cell death, were also attenuated. Variable inhibition of TRPA1, ER stress, and MUC5AC mRNA induction was observed using selected chemicals identified in Vasaka tea including vasicine, vasicinone, apigenin, 9-oxoODE, and 9,10-EpOME. 9,10-EpOME and apigenin were the most cytoprotective and mucosuppressive. Cytochrome P450 1A1 mRNA was also induced by Vasaka tea and wood smoke particles. Inhibition of CYP1A1 enhanced ER stress and MUC5AC mRNA expression, suggesting a role in producing protective oxylipins in stressed cells. The results provide mechanistic insights and support for the purported benefits of Vasaka tea in treating lung inflammatory conditions, raising the possibility of further development as a preventative therapy.
2023-07-05 | GSE232172 | GEO
Project description: Not available
| S-EPMC8784167 | biostudies-literature
Project description:To understand the immunomodulation roles of Ixodes scapularis protein disulfide isomerase A6 (IsPDIA6), we utilized RNA sequencing (RNA-seq) to investigate the effect of IsPDIA6 on the murine transcriptome.
2024-10-14 | GSE273486 | GEO
Project description:Therapeutic Targeting of Protein Disulfide Isomerase PDIA1 in Multiple Myeloma
| PRJNA702993 | ENA
Project description: Not available
| S-EPMC11335981 | biostudies-literature
Project description:AGR2 is an oncogenic endoplasmic reticulum (ER)-resident protein disulfide isomerase. AGR2 protein has a relatively unique property for a chaperone in that it can bind sequence-specifically to a peptide motif (TTIYY). A synthetic TTIYY-containing peptide column can be used to affinity-purify AGR2 from crude lysates highlighting peptide selectivity in complex mixtures. Hydrogen-deuterium exchange mass spectrometry localized the dominant region in AGR2 that interacts with the TTIYY peptide to within a structural loop from amino acids 131-135 (VDPSL). A peptide binding site consensus of Tx[IL][YF][YF] was developed for AGR2 by measuring its activity against a alanine mutagenized synthetic peptide library. Screening the human proteome for proteins harboring this consensus motif revealed an enrichment in transmembrane proteins and we focus on validating EpCAM as one such oncogenic protein. Recombinant AGR2 and EpCAM proteins formed a dose-dependent protein-protein interaction in vitro. Proximity ligation assays demonstrated that endogenous AGR2 and EpCAM protein associate in cells. Introducing a single alanine mutation in EpCAM at Tyr251 attenuated its binding to AGR2 in vitro and in cells. Hydrogen-deuterium exchange mass spectrometry was used to identify a stable binding site for AGR2 on EpCAM, adjacent to the TILYY motif and surrounding EpCAM’s detergent binding site. Together, these data define a dominant peptide-binding site on AGR2 that mediates its specific peptide-binding function. A model client protein, EpCAM, is proposed for AGR2 to study how an ER-resident chaperone can dock specifically and regulate assembly of a protein destined for the secretory pathway.
2018-01-22 | PXD005782 | Pride
Project description: Not available
| S-EPMC5321798 | biostudies-literature