Transcription profiling of mouse subconfluent and confluent aortic endothelial cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Leni Moldovan
PROVIDER: E-GEOD-1576 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Gene expression changes in subconfluent mouse aortic endothelial cells were compared with confluent endothelial cells. Compartmental analysis showed coordinater response in several endothelial-specific functions and organelles (endoplasmic reticulum, Golgi, lysosomes, peroxisomes) which were downregulated, and upregulation of the microtubular system and proliferation. Keywords = endothelium Keywords = confluent Keywords = subconfluent Keywords = organelles Keywords: other
2005-01-20 | GSE1576 | GEO
Project description:Crucial metabolic functions of peroxisomes rely on a variety of peroxisomal membrane proteins (PMPs). While mRNA transcripts of PMPs were shown to be colocalized with peroxisomes, the process by which PMPs efficiently couple translation with targeting to the peroxisomal membrane remained elusive. Here, we combine quantitative electron microscopy with proximity-specific ribosome profiling and reveal that translation of specific PMPs occurs on the surface of peroxisomes in the yeast Saccharomyces cerevisiae. This places peroxisomes alongside chloroplasts, mitochondria, and the endoplasmic reticulum as organelles that use localized translation for ensuring correct insertion of hydrophobic proteins into their membranes. Moreover, the correct targeting of these transcripts to peroxisomes is crucial for peroxisomal and cellular function, emphasizing the importance of localized translation for cellular physiology.
2022-01-12 | GSE113567 | GEO
Project description:Organelles from Pichia, either grown on glucose or methanol were purified and analysed using LC-ESI-MS. Two biological replicates each had been analyzed leading to four replicate data sets for every organelle. Organelles analyzed: cis golgi, trans golgi, plasma membrane, microsomes, cytosol, vacuole, peroxisomes and mitochondria
2020-05-26 | PXD011220 | Pride
Project description:The compartmentalisation of distinct organelles within eukaryotic cells is essential for their diverse functions, however, how their structures and functions depend on each other has not been systematically explored. We combined a fluorescent reporter of mitochondrial stress with genome-wide CRISPR knockout screening and identified networks of genes involved in the biogenesis and metabolism of diverse organelles. Targeted organelle gene knockouts identified that defects in peroxisomes, Golgi, and ER cause mitochondrial fragmentation and dysfunction. Correlative light and electron microscopy analysed using artificial intelligence-directed voxel extraction revealed in unprecedented detail how impaired mitochondrial interactions with diverse organelles caused cell-wide defects in their morphology and biogenesis. Multi-omics analyses identified a unified proteome stress response and global shifts in lipid and glycoprotein homeostasis that are elicited when organelle biogenesis is compromised. Our comprehensive resource has defined metabolic and morphological interactions between organelles that can be mined to understand how changes in organelle components drive diverse cellular pathologies.
2023-10-13 | GSE201573 | GEO
Project description:Intracellular Salmonella resides and multiplies in cholesterol-rich specialized compartment called Salmonella-containing vacuoles (SCVs) and avoids fusion with acidic lysosomes. Given, lysosomes are primary organelle that redistributes LDL derived cholesterol to other organelles; we questioned how lysosomal cholesterol can be transported to SCV. We demonstrate here that peroxisomes are recruited to SCVs in human primary macrophages, epithelial cells and functions as pro-bacterial organelles. Further, this interaction is assisted by SseI, a Salmonella effector protein containing mammalian peroxisome targeting sequence. SseI localizes to peroxisome, interacts and activates a host Ras GTPase, ARF-1 on the peroxisome membrane. Activation of ARF-1 leads to recruitment of phosphatidylinsolitol-5- phosphate-4 kinase to generate phosphatidylinsolitol-4-5-bisphosphate on peroxisomes. Accordingly, the ΔsseI strain showed reduced virulence in cell lines and during mice infection. Taken together, our work identified a fascinating mechanism by which a pathogen targets host organelles via its secretory effectors and exploits host metabolic intermediates for its intracellular proliferation.
2024-10-28 | PXD055151 | Pride
Project description:Cholesterol and phosphoinositides (PI) are two critically important lipids that are found in cellular membranes and dysregulated in many disorders. Therefore, uncovering molecular pathways connecting these essential lipids may offer new therapeutic insights. We report that loss of function of lysosomal Niemann-Pick Type C1 (NPC1) cholesterol transporter, which leads to neurodegenerative NPC disease, initiates a signaling cascade that alters the cholesterol/phosphatidylinositol 4-phosphate (PtdIns4P) countertransport cycle between Golgi-endoplasmic reticulum (ER), as well as lysosome-ER membrane contact sites (MCS). Central to these disruptions is increased recruitment of phosphatidylinositol 4-kinases-PI4KIIα and PI4KIIIβ-which boosts PtdIns4P metabolism at Golgi and lysosomal membranes. Aberrantly increased PtdIns4P levels elevate constitutive anterograde secretion from the Golgi complex, and mTORC1 recruitment to lysosomes. NPC1 disease mutations phenocopy the transporter loss of function and can be rescued by inhibition or knockdown of either key phosphoinositide enzymes or their recruiting partners. In summary, we show that the lysosomal NPC1 cholesterol transporter tunes the molecular content of Golgi and lysosome MCS to regulate intracellular trafficking and growth signaling in health and disease.
2021-09-15 | MTBLS2612 | MetaboLights
Project description:Subconfluent and confluent aortic endothelial cells
| PRJNA90341 | ENA
Project description:Eukaryotic cells contain several membrane-separated organelles to compartmentalize distinct metabolic reactions. However, it has remained unclear how these organelle systems are coordinated, when cells adapt metabolic pathways to support their development, survival or effector functions. Here we present OrgaPlexing, a multispectral organelle imaging approach for the comprehensive mapping of six key metabolic organelles and their interactions. We use this analysis on macrophages, immune cells that undergo rapid metabolic switches upon sensing bacterial and inflammatory stimuli. Our results identify lipid droplets (LDs) as primary inflammatory responder organelle, which forms three- and four-way interactions with other organelles. While clusters with endoplasmic reticulum (ER) and mitochondria (M-ER-LD unit) help supply fatty acids for LD growth, the additional recruitment of peroxisomes (M-ER-P-LD unit) supports fatty acid efflux from LDs. Interference with individual components of these units has direct functional consequences for inflammatory lipid synthesis. Together, we show that macrophages form functional multi-organellar units (MOUs) to support metabolic adaptation, and provide an experimental strategy to identify organelle-metabolic signaling hubs.
2024-05-03 | GSE235484 | GEO
Project description:Abstract Von Willebrand factor (VWF) is a multimeric hemostatic protein primarily synthesized in endothelial cells (ECs). VWF is stored in endothelial storage organelles, the Weibel-Palade bodies (WPBs), whose biogenesis strongly depends on VWF anterograde trafficking and Golgi architecture. Elongated WPB morphology is correlated to longer VWF strings with better adhesive properties. We previously identified the SNARE SEC22B, which is involved in anterograde ER-to-Golgi transport, as a novel regulator of WPB elongation. To elucidate novel determinants of WPB morphology we explored endothelial SEC22B interaction partners in a mass spectrometry-based approach, identifying the Golgi SNARE Syntaxin 5 (STX5). We established STX5 knockdown in ECs using shRNA-dependent silencing and analyzed WPB and Golgi morphology, using confocal and electron microscopy. STX5-depleted ECs exhibited extensive Golgi fragmentation and decreased WPB length, which was associated with reduced intracellular VWF levels, and impaired stimulated VWF secretion. However, the secretion incompetent organelles in shSTX5 cells maintained WPB markers such as Angiopoietin 2, P-selectin, Rab27A, and CD63. Taken together, our study has identified SNARE protein STX5 as a novel regulator of WPB biogenesis
2022-01-27 | PXD027516 | Pride
Project description:Signal peptide peptidase-like 2c (SPPL2c) is the only member of the GxGD type intramembrane-cleaving aspartyl proteases that so far has not been assigned any substrates and thus its capability of proteolysis and its physiological function remain enigmatic. Based on a surprisingly high expression of SPPL2c in elongated spermatids we applied proteomics on a cellular model system with ectopic expression of SPPL2c and identified a variety of candidate substrates. The majority of these candidate substrates clusters to the biological process of vesicular trafficking. Analysis of selected SNARE proteins reveals proteolytic processing by SPPL2c that impairs vesicular transport and causes retention of cargo proteins in the endoplasmic reticulum. As a consequence, the integrity of subcellular compartments, in particular the Golgi, is disturbed. This may be the trigger for the compartmental reorganization observed during spermatogenesis, which finally results in loss of the majority of endoplasmic reticulum, Golgi and parts of the cytosol in the mature sperm.
2019-02-12 | PXD011923 | Pride