Impaired store-operated Ca2+ entry in mouse epidermis
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE306726 | GEO | 2025/10/15
REPOSITORIES: GEO
Similar Datasets
Project description:T follicular helper (TFH) cells promote affinity maturation of B cells in germinal centers (GCs), whereas T follicular regulatory (TFR) cells limit GC reaction. Store-operated Ca2+ entry (SOCE) through Ca2+ release-activated Ca2+ (CRAC) channels mediated by STIM and ORAI proteins is a fundamental signaling pathway in T lymphocytes. Here we show that SOCE is required for the differentiation and function of both TFH and TFR cells. Conditional deletion of Stim1 and Stim2 genes in T cells or Treg cells results in spontaneous autoantibody production and humoral autoimmunity. Conversely, antibody-mediated immune responses following viral infection critically depend on SOCE in TFH cells. Mechanistically, STIM1 and STIM2 control early TFR and TFH cell differentiation through NFAT-mediated IRF4, BATF and Bcl-6 expression. SOCE plays a dual role in GC response by controlling TFH and TFR cell function, thus enabling protective B cell responses and preventing humoral autoimmunity. RNAseq analyses of WT and Stim1Stim2 DKO follicular T cells and non-follicular T cells; 4-6 mice per cohort in duplicates. Mice were infected for 10 days with LCMV.
2016-03-10 | E-GEOD-79039 | biostudies-arrayexpress
Project description:T follicular helper (TFH) cells promote affinity maturation of B cells in germinal centers (GCs), whereas T follicular regulatory (TFR) cells limit GC reaction. Store-operated Ca2+ entry (SOCE) through Ca2+ release-activated Ca2+ (CRAC) channels mediated by STIM and ORAI proteins is a fundamental signaling pathway in T lymphocytes. Here we show that SOCE is required for the differentiation and function of both TFH and TFR cells. Conditional deletion of Stim1 and Stim2 genes in T cells or Treg cells results in spontaneous autoantibody production and humoral autoimmunity. Conversely, antibody-mediated immune responses following viral infection critically depend on SOCE in TFH cells. Mechanistically, STIM1 and STIM2 control early TFR and TFH cell differentiation through NFAT-mediated IRF4, BATF and Bcl-6 expression. SOCE plays a dual role in GC response by controlling TFH and TFR cell function, thus enabling protective B cell responses and preventing humoral autoimmunity.
2016-03-10 | GSE79039 | GEO
Project description:Abstarct:Mutations in the endoplasmic reticulum (ER) Ca2+ sensor stromal interaction molecule 1 (STIM1) result is a number of disease states including abnormal enamel formation. However, these defects in enamel have remained unclear given a lack of animal models available. We generated Stim1/2K14Cre mice to ablate the activity of STIM1 and its homologue STIM2 in enamel cells. These mice showed impaired Ca2+ entry in enamel cells and although enamel formed, it was severely hypomineralized and mechanically weak. RNA-sequencing of enamel cells provided a global overview of loss of Ca2+ sensor activity. ER stress markers associated with unfolded protein response (UPR) were increased. Cell morphology was altered showing loss of the typical ruffled-border and mislocalized mitochondria. We also identified decreased glutathione system and potentially associated with this, increased ROS and abnormal mitochondria. The Ca2+ extrusion system and enamel gene expression were also altered. These data might represent the first in vivo study linking Stim1/2 ablation with increased UPR function, decreased glutathione metabolism, increased ROS and abnormal mitochondria. Loss of ER Ca2+ sensors Stim1/2 in enamel cells has substantial detrimental effects at the cell and mineral phase level.
2017-01-17 | GSE93655 | GEO
Project description:This series of microarray experiments monitored the gene expression profiles for monoclonal cell lines (derived from HEK-293 parental cell culture) with high (H1, H15, H24, H36, H39) or low (L3, L28, L29) levels of store-operated Ca2+ entry (SOCE). For selection of clones, HEK-293 cells were loaded with indo-1 and sorted by FACS on the basis of their cyclopiazonic acid (CPA)-stimulated Ca2+ entry. Monoclonal cell lines were selected from the sorted cells and their levels of SOCE confirmed by monitoring thapsigargin-stimulated Ba2+ entry. Total RNA was extracted from cells immediately after removal from their growth environment. RNA was processed and hybridized to the Affymetrix HG-U133A chip. Two parallel hybridizations were done for each RNA preparation from each monoclonal cell line or from the parental HEK-293 cell culture.
2007-08-03 | E-GEOD-1309 | biostudies-arrayexpress
Project description:This series of microarray experiments monitored the gene expression profiles for monoclonal cell lines (derived from HEK-293 parental cell culture) with high (H1, H15, H24, H36, H39) or low (L3, L28, L29) levels of store-operated Ca2+ entry (SOCE). For selection of clones, HEK-293 cells were loaded with indo-1 and sorted by FACS on the basis of their cyclopiazonic acid (CPA)-stimulated Ca2+ entry. Monoclonal cell lines were selected from the sorted cells and their levels of SOCE confirmed by monitoring thapsigargin-stimulated Ba2+ entry. Total RNA was extracted from cells immediately after removal from their growth environment. RNA was processed and hybridized to the Affymetrix HG-U133A chip. Two parallel hybridizations were done for each RNA preparation from each monoclonal cell line or from the parental HEK-293 cell culture. Keywords: parallel sample
2004-06-08 | GSE1309 | GEO
Project description:Pharmacological manipulation of lysosome membrane integrity or ionic movements is a key strategy for probing lysosomal involvement in cellular processes. However, we have found an unexpected inhibition of store-operated Ca2+ entry (SOCE) by these agents. Dipeptides [glycyl-L-phenylalanine 2-naphthylamide (GPN) and L-leucyl-L-leucine methyl ester] that are inducers of lysosomal membrane permeabilization (LMP) uncoupled endoplasmic reticulum Ca2+-store depletion from SOCE by interfering with Stim1 oligomerization and/or Stim1 activation of Orai. Similarly, the K+/H+ ionophore, nigericin, that rapidly elevates lysosomal pH, also inhibited SOCE in a Stim1-dependent manner. In contrast, other strategies for manipulating lysosomes (bafilomycin A1, lysosomal re-positioning) had no effect upon SOCE. Finally, the effects of GPN on SOCE and Stim1 was reversed by a dynamin inhibitor, dynasore. Our data show that lysosomal agents not only release Ca2+ from stores but also uncouple this release from the normal recruitment of Ca2+ influx.
| S-EPMC7860125 | biostudies-literature
Project description:Primary Sjogren’s syndrome (pSS) is an autoimmune disease characterized by xerostomia (dry mouth), lymphocytic infiltration into salivary glands and the presence of SSA and SSB autoantibodies. Xerostomia is caused by hypofunction of the salivary glands and has been considered a driver in pSS development. Saliva production is regulated by sympathetic input into the gland initiating intracellular Ca2+ signals that activate the store operated Ca2+ entry (SOCE) pathway eliciting sustained Ca2+ influx. SOCE is mediated by the STIM1 and STIM2 proteins and the ORAI1 Ca2+ channel. However, there are no studies on the effects of lack of STIM1/2 function in salivary acini in animal models or its impact on pSS. Here we report that male and female mice lacking Stim1 and Stim2 (Stim1/2K14Cre) in salivary glands hyposalivate upon pilocarpine stimulation and showed reduced intracellular Ca2+ levels via SOCE in parotid acini. Bulk RNASeq of the parotid glands of Stim1/2K14Cre showed a decrease in Stim1/2 genes but not in other Ca2+ associated genes mediating saliva fluid secretion, yet SOCE was functionally required for the activation of the Ca2+ activated chloride channel ANO1. Ageing Stim1/2K14Cre mice showed no evidence of lymphocytic infiltration in the glands or elevated levels of SSA or SSB autoantibodies in the serum which may be linked to the downregulation of the toll-like receptor 8 (Tlr8) in Stim1/2K14Cre mice. This is supported by an increase in TLR8 gene expression in a salivary gland cell line following SOCE stimulation. Moreover, salivary gland biopsies of pSS patients showed increased STIM1 and TLR8 expression. These results implicate SOCE as an important activator of ANO1 and saliva fluid secretion in salivary glands but loss of SOCE does not result in pSS. Importantly, our data suggest a link between SOCE and TLR8 signaling which may have implications in inflammatory responses in salivary glands.
2025-02-19 | GSE251691 | GEO
Project description:Calcium signals are initiated in immune cells by the process of store-operated calcium entry (SOCE), where receptor activation triggers transient calcium release from the endoplasmic reticulum, followed by opening of plasma membrane calcium-release activated calcium (CRAC) channels. ORAI1, ORAI2 and ORAI3 are known to comprise the CRAC channel, however the contributions of individual isoforms to neutrophil function is not well understood. Here we show that loss of ORAI1 partially decreases calcium influx while loss of both ORAI1 and ORAI2 completely abolishes store-operated calcium entry. In other immune cell types, loss of ORAI2 enhances SOCE. In contrast, we find that ORAI2-deficient neutrophils display decreased calcium influx, which is correlated with measurable differences in regulation of neutrophil membrane potential via KCa3.1. Decreased SOCE in ORAI1-, ORAI2- and ORAI1/2-deficient neutrophils impairs multiple neutrophil functions including phagocytosis, degranulation, leukotriene and ROS production, rendering ORAI1/2-deficient mice highly susceptible to staphylococcal infection. This study demonstrates that ORAI1 and ORAI2 are the primary components of the neutrophil CRAC channel and identifies novel subpopulations of neutrophils where cell membrane potential functions as a rheostat to modulate the SOCE response. These findings have implications for new mechanisms that modulate neutrophil function during infection, acute and chronic inflammatory conditions, and cancer.
2020-09-01 | GSE157200 | GEO
Project description:Transcriptional regulation by Store-operated Calcium Entry (SOCE) is well studied in non-excitable cells. However, the role of SOCE has been poorly documented in neuronal cells with more complicated calcium dynamics. Previous reports demonstrated a requirement of neuronal SOCE for Drosophila flight. We identified the early pupal stage to be critical and used RNA-sequencing to identify SOCE mediated gene expression changes in the developing Drosophila pupal nervous system. We down-regulated dStim, the endoplasmic reticular calcium sensor and a principal component of SOCE in the nervous system for a 24h period during pupal development, and compared wild type and knockdown transcriptional profiles, immediately after knockdown as well as after a 36h recovery period. We found that dStim knockdown altered the expression of a number of genes. We also characterized one of the down-regulated genes, Ral for its role in flight. Thus, we identify neuronal SOCE as a mechanism that regulates expression of a number of genes during the development of the pupal nervous system. These genes can be further studied in the context of pupal nervous system development.
2017-03-21 | GSE89168 | GEO
Project description:Calcium (Ca2+) signaling plays a dichotomous role in cellular biology, controlling cell survival and proliferation on the one hand and cellular toxicity and cell death on the other. Store-operated Ca2+ entry (SOCE) by CRAC channels represents a major pathway for Ca2+ entry in non-excitable cells. The CRAC channel has two key components, the endoplasmic reticulum Ca2+ sensor stromal interaction molecule (STIM) and the plasma-membrane Ca2+ channel Orai. Physical coupling between STIM and Orai opens the CRAC channel and the resulting Ca2+ flux is regulated by a negative feedback mechanism of slow Ca2+ dependent inactivation (SCDI). The identification of the SOCE-associated regulatory factor (SARAF) and investigations of its role in SCDI have led to new functional and molecular insights into how SOCE is controlled. In this review, we provide an overview of the functional and molecular mechanisms underlying SCDI and discuss how the interaction between SARAF, STIM1, and Orai1 shapes Ca2+ signaling in cells.
| S-EPMC8391525 | biostudies-literature