Knocking down CAVIN1 in WPMY-1 normal prostate stromal cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE146229 | GEO | 2022/01/19
REPOSITORIES: GEO
Similar Datasets
Project description:Reducing insulin/IGF-1 signaling (IIS) extends lifespan, promotes protein homeostasis (proteostasis) and elevates stress resistance of worms, flies and mammals. How these functions are orchestrated across the organism is only partially understood. One prominent group of IIS-regulated encode for lipid metabolizing enzymes. Thus, we asked whether IIS reduction modulates the protein content and functionality of membranal lipid assemblies. We discovered that in the nematode Caenorhabditis elegans, the IIS positively regulates the expression of caveolin-1 (cav-1), a gene which is primarily expressed in neurons of the adult worm and underlies the formation of caveolae, a subtype of lipid microdomains that serve as platforms for signaling complexes. Accordingly, IIS reduction lowers cav-1 expression and lessens the quantity of neuronal caveolae. Reduced cav-1 expression extends lifespan and mitigates toxic protein aggregation by modulating the expression of aging-regulating and signaling-promoting genes. Our findings define caveolae as aging-governing signaling centers and underscore the potential for cav-1 as a novel therapeutic target for the promotion of healthy aging.
2018-05-09 | PXD009704 | Pride
Project description:Caveolae are cell membrane invaginations that are highly abundant in adipose tissue, endothelial cells and lung and are present at lower levels in other tissues. The formation of caveolae is dependent of the expression of various structural proteins that serve as scaffolding for these membrane invaginations. Cavin1 is a newly identified structural protein whose deficiency leads to absence of caveolae formation and to the development of a lipodystrophic phenotype. In this study we show Cavin1 expression is critical for regulating macrophage number and gene-expression (phenotype) in the lung. We used microarrays to detail the global programme of gene expression in alveolar macrophage in a Cavin1 knock-out mouse and identified distinct classes of dysregulated genes during this process.
2013-06-07 | GSE42169 | GEO
Project description:Caveolae are cell membrane invaginations that are highly abundant in adipose tissue, endothelial cells and lung and are present at lower levels in other tissues. The formation of caveolae is dependent of the expression of various structural proteins that serve as scaffolding for these membrane invaginations. Cavin1 is a newly identified structural protein whose deficiency leads to absence of caveolae formation and to the development of a lipodystrophic phenotype. In this study we show Cavin1 expression is critical for regulating macrophage number and gene-expression (phenotype) in the lung. We used microarrays to detail the global programme of gene expression in alveolar macrophage in a Cavin1 knock-out mouse and identified distinct classes of dysregulated genes during this process. Bronchoalveolar Lavage performed though a 22-gauge needle tied in place to trachea with PBS containing 0.5 mM ethylenediaminetetraacetic acid (EDTA). Aliquots of 0.5 to 1 ml were instilled into the lungs under direct observation to ensure that all segments of lung were inflated, and aspirated back into the syringe. This was repeated five times per mouse. RNA was extracted from extracted alveolar macrophages and hybridized to Affymetrix microarrays for gene expression analysis.
2013-06-07 | E-GEOD-42169 | biostudies-arrayexpress
Project description:Endothelial cell (EC) CD36 controls tissue fatty acid (FA) uptake. Here we examined how ECs transfer FAs. FA interaction with apical membrane CD36 induced Src phosphorylation of caveolin-1 tyrosine-14 (Cav-1Y14) and ceramide generation in caveolae. Fission of the caveolae yielded vesicles containing FAs, CD36 and ceramide that were secreted basolaterally as small (80-100nm) exosome-like extracellular vesicles (sEVs). We visualized EC transfer of FAs in sEVs to underlying myotubes in transwells. In mice with EC-expression of the exosome marker emeraldGFP-CD63, muscle fibers accumulated circulating FAs in emGFP-labeled puncta. The FA-sEV pathway was mapped through its suppression by CD36 depletion, blocking actin-remodeling, Src inhibition, Cav-1Y14 mutation, and neutral sphingomyelinase 2 inhibition. Suppression of sEV formation in mice reduced muscle FA uptake, raised circulating FAs, which remained in blood vessels, and lowered glucose, mimicking prominent Cd36-/- phenotypes. The findings show that FA uptake influences membrane ceramide, endocytosis, and EC communication with parenchymal cells.
2023-07-02 | GSE235988 | GEO
Project description:Caveolae are plasma membrane invaginations found in most cells of mammals. Caveolin-1 (Cav1) encodes a major protein of the lipid rafts of these membrane structures. Cav1-null mice, though viable, show various phenotypic defects. At an early adult age, these mice show brain aging that resemble brain of one and half year old wildtype mice, and exhibit symptoms that are hallmarks of Alzheimer’s disease. It is not known if the ablation of Cav1 in these mice impacts the brain at the fetal stage that then influences brain function later in life. Single nuclei RNA sequencing was performed with fetal brain of wildtype and Cav1 knockout mice. Results showed that specific metabolism genes were differentially expressed bewteen different glial cells.
2023-09-20 | GSE214759 | GEO
Project description:Caveolae are specialized domains of the plasma membrane. Formation of these invaginations is dependent on the expression of Caveolin-1 or -3 and proteins of the cavin family. In response to stress, caveolae disassemble and cavins are released from caveolae, allowing cavins to potentially interact with intracellular targets. Here, we describe the intracellular (non-plasma membrane) cavin interactome using biotin affinity proteomics and mass spectrometry. We validate 47 potential cavin-interactor proteins using a cell-free expression system and protein-protein binding assays. These data, together with pathway analyses, revealed novel roles for cavin proteins in metabolism and stress signaling. We validated the interaction between one candidate interactor protein, protein phosphatase 1 alpha (PP1α), and Cavin-1 and -3 and show that UV treatment causes release of Cavin3 from caveolae allowing interaction with, and inhibition of, PP1α. This interaction increases H2AX phosphorylation to stimulate apoptosis, identifying a pro-apoptotic signaling pathway from surface caveolae to the nucleus.
2019-07-23 | PXD014094 | Pride
Project description:Caveolae are specialized domains of the plasma membrane. Formation of these invaginations is dependent on the expression of Caveolin-1 or -3 and proteins of the cavin family. In response to stress, caveolae disassemble and cavins are released from caveolae, allowing cavins to potentially interact with intracellular targets. Here, we describe the intracellular (non-plasma membrane) cavin interactome using biotin affinity proteomics and mass spectrometry. We validate 47 potential cavin-interactor proteins using a cell-free expression system and protein-protein binding assays. These data, together with pathway analyses, revealed novel roles for cavin proteins in metabolism and stress signaling. We validated the interaction between one candidate interactor protein, protein phosphatase 1 alpha (PP1α), and Cavin-1 and -3 and show that UV treatment causes release of Cavin3 from caveolae allowing interaction with, and inhibition of, PP1α. This interaction increases H2AX phosphorylation to stimulate apoptosis, identifying a pro-apoptotic signaling pathway from surface caveolae to the nucleus.
2019-07-23 | PXD014081 | Pride
Project description:Caveolae are plasma membrane invaginations found in most cells of mammals. Caveolin-1 (Cav1) encodes a major protein of the lipid rafts of these membrane structures. Cav1-null mice, though viable, show various phenotypic defects. At an early adult age, these mice show brain aging that resemble brain of one and half year old wildtype mice, and exhibit symptoms that are hallmarks of Alzheimer’s disease. It is not known if the ablation of Cav1 in these mice impacts the brain at the fetal stage that then influences brain function later in life. RNA-seq was performed to profile gene expression of fetal brain (gestation day 15) and aging brain (week 70) of Cav1 knockout mice. The data was comapred with genes expression data of fetal brain (gestation day 15) and aging brain (week 70) of wildtype mice from our earlier study.
2023-09-20 | GSE215139 | GEO
Project description:Obesity has emerged as a worldwide problem in human health. Dietary lipids are taken up and transported via lymphatics into the circulatory system. During this process, lipids pass the mesenteric lymph node (mLN). These organs filter the lymph fluid for foreign antigens to induce and control immune responses. Alteration of that function during obesity has only slightly been studied. Here, we characterize changes within the microarchitecture of the mLN during high levels of lipid transport and highlight the role of stromal cells. Microarray experiments detected gene probes expressed by mLN stromal cells. Transmission electron microscopy enabled us to identify lipid droplets in different stromal cells, and in macrophages. Sizes, numbers and intercellular distances increased after 10 weeks of a high-fat diet. Thus, we propose that changes in the microarchitecture and increased accumulation of lipid droplets in stromal cells and macrophages have an influence on the immunological function of the mLN.
2020-05-14 | GSE138594 | GEO
Project description:Obesity has emerged as a worldwide problem in human health. Dietary lipids are taken up and transported via lymphatics into the circulatory system. During this process, lipids pass the mesenteric lymph node (mLN). These organs filter the lymph fluid for foreign antigens to induce and control immune responses. Alteration of that function during obesity has only slightly been studied. Here, we characterize changes within the microarchitecture of the mLN during high levels of lipid transport and highlight the role of stromal cells. Microarray experiments detected gene probes expressed by mLN stromal cells. Transmission electron microscopy enabled us to identify lipid droplets in different stromal cells, and in macrophages. Sizes, numbers and intercellular distances increased after 10 weeks of a high-fat diet. Thus, we propose that changes in the microarchitecture and increased accumulation of lipid droplets in stromal cells and macrophages have an influence on the immunological function of the mLN.
2020-05-14 | GSE138593 | GEO