A5027752685- Cellular transport and secretion
- S100 Proteins and Annexins
- Lipid Membrane Structure and Behavior
- Caveolin-1 and cellular processes
- Pancreatic function and diabetes
- Liver physiology and pathology
- Glycosylation and Glycoproteins Research
- Erythrocyte Function and Pathophysiology
- Endoplasmic Reticulum Stress and Disease
- Cell Adhesion Molecules Research
- Protein Kinase Regulation and GTPase Signaling
- Liver Disease Diagnosis and Treatment
- Lipid metabolism and biosynthesis
- Protease and Inhibitor Mechanisms
- Ion Transport and Channel Regulation
- Ion channel regulation and function
- Lysosomal Storage Disorders Research
- Signaling Pathways in Disease
- Drug Transport and Resistance Mechanisms
- Cholesterol and Lipid Metabolism
- Cell death mechanisms and regulation
- Metabolism, Diabetes, and Cancer
- Connexins and lens biology
- Calcium signaling and nucleotide metabolism
- Cellular Mechanics and Interactions
Consorci Institut D'Investigacions Biomediques August Pi I Sunyer
2016-2025
Universitat de Barcelona
2016-2025
Departament de Salut
2018-2025
Medicina
2015
University of Buenos Aires
2007
The University of Queensland
2006
Max Planck Institute of Molecular Cell Biology and Genetics
2006
Consejo Superior de Investigaciones Científicas
2006
Institut d'Investigacions Biomèdiques de Barcelona
2006
St Vincent's Hospital Sydney
2006
Abstract Exosomes are vesicles secreted to the extracellular environment through fusion with plasma membrane of specific endosomes called multivesicular bodies (MVB) and mediate cell-to-cell communication in many biological processes. Posttranslational modifications involved sorting proteins into exosomes. Here we identify ISGylation as a ubiquitin-like modification that controls exosome release. induction decreases MVB numbers impairs secretion. Using ISG15-knockout mice expressing...
Cells drop a bomb on pathogens Lipid droplets (LDs) accumulate in cells to serve as lipid storage organelles. They are also an attractive source of nutrients for many pathogens. Bosch et al. show that various proteins involved innate immunity form complexes LDs response bacterial lipopolysaccharide (see the Perspective by Green). Upon activation, became physically uncoupled from mitochondria, driving shift oxidative phosphorylation aerobic glycolysis. This work highlights ability both kill...
Control of lipid droplet (LD) nucleation and copy number are critical, yet poorly understood, processes. We use model peptides that shift from the endoplasmic reticulum (ER) to LDs in response fatty acids characterize initial steps LD formation occurring lipid-starved cells. Initially, arriving lipids rapidly packed resistant starvation (pre-LDs). Pre-LDs restricted ER microdomains with a stable core neutral lipids. Subsequently, first round "emerging" is nucleated, providing additional...
Abstract Lipid droplets (LDs) are intracellular organelles that provide fatty acids (FAs) to cellular processes including synthesis of membranes and production metabolic energy. While known move bidirectionally along microtubules (MTs), the role LD motion whether it facilitates interaction with other unclear. Here we show during nutrient starvation, LDs mitochondria relocate on detyrosinated MT from cell centre adopt a dispersed distribution. In periphery, LD–mitochondria interactions...
Liver regeneration is an orchestrated cellular response that coordinates cell activation, lipid metabolism, and division. We found caveolin-1 gene–disrupted mice ( cav1 –/– mice) exhibited impaired liver low survival after a partial hepatectomy. Hepatocytes showed dramatically reduced droplet accumulation did not advance through the division cycle. Treatment of with glucose (which predominant energy substrate when compared to lipids) drastically increased reestablished progression Thus,...
This study addressed the contribution of acidic sphingomyelinase (ASMase) in TNF-α–mediated hepatocellular apoptosis. Cultured hepatocytes depleted mitochondrial glutathione (mGSH) became sensitive to TNF-α, undergoing a time-dependent apoptotic cell death preceded by membrane depolarization, cytochrome c release, and caspase activation. Cyclosporin A treatment rescued mGSH-depleted from TNF-α–induced death. In contrast, deficient ASMase were resistant but exogenous ASMase. Furthermore,...
Caveolins are a crucial component of caveolae but have also been localized to the Golgi complex, and, under some experimental conditions, lipid bodies (LBs). The physiological relevance and dynamics LB association remain unclear. We now show that endogenous caveolin-1 caveolin-2 redistribute LBs in loaded A431 FRT cells. Association with is regulated reversible; removal fatty acids causes caveolin rapidly leave body. by subcellular fractionation, light electron microscopy during first hours...
Caveolins are a crucial component of plasma membrane (PM) caveolae but have also been localized to intracellular compartments, including the Golgi complex and lipid bodies. Mutant caveolins associated with human disease show aberrant trafficking PM accumulation. We now that pool mainly newly synthesized protein is detergent-soluble predominantly in monomeric state, contrast surface pool. Caveolin at not recognized by specific caveolin antibodies unless cholesterol depleted. Exit from...
Alcoholic and nonalcoholic liver steatosis steatohepatitis are characterized by the massive accumulation of lipid droplets (LDs) in cytosol hepatocytes. Although LDs ubiquitous dynamic organelles found cells a wide range organisms, little is known about mechanisms sites LD biogenesis. To examine participation these pathophysiological disorders steatotic livers, we used combination mass spectrometry (matrix‐assisted laser desorption ionization‐time flight LC‐MS electrospray) Western blot...
Severe liver diseases are characterized by expansion of progenitor cells (LPC), which correlates with disease severity. However, the origin and role LPC in physiology hepatic injury remains a contentious topic. We found that ductular reaction human cirrhotic livers express hepatocyte nuclear factor 1 homeobox B (HNF1β). HNF1β expression was not present newly generated epithelial cell adhesion molecule (EpCAM)-positive hepatocytes. In order to investigate HNF1β-expressing we used...
Mitochondrial cholesterol accumulation is a hallmark of alcoholic and non-alcoholic fatty liver diseases impairs the function specific solute carriers through changes in membrane physical properties. However, its impact on mitochondrial respiration organization respiratory supercomplexes has not been determined so far. Here we fed mice cholesterol-enriched diet (HC) supplemented with sodium cholate to examine effect function. HC feeding increased content, which downregulated Srebp2 Hmgcr...
Inhibition of cholesterol export from late endosomes causes cellular imbalance, including depletion in the trans-Golgi network (TGN). Here, using Chinese hamster ovary (CHO) Niemann-Pick type C1 (NPC1) mutant cell lines and human NPC1 fibroblasts, we show that altered levels at TGN/endosome boundaries trigger Syntaxin 6 (Stx6) accumulation into VAMP3, transferrin, Rab11-positive recycling (REs). This increases Stx6/VAMP3 interaction interferes with αVβ3 α5β1 integrins migration, possibly a...
Abstract Acute inflammation can either resolve through immunosuppression or persist, leading to chronic inflammation. These transitions are driven by distinct molecular and metabolic reprogramming of immune cells. The anti-diabetic drug Metformin inhibits acute mechanisms still not fully understood. Here, we report that the anti-inflammatory reactive-oxygen-species-inhibiting effects depend on expression plasticity factor ZEB1 in macrophages. Using mice lacking Zeb1 their myeloid cells human...
Following cell activation, hepatic stellate cells (HSCs) acquire proinflammatory and profibrogenic properties. We investigated whether activated HSCs also display immune Here we show that cultured human express membrane proteins involved in antigen presentation, including members of the HLA family (HLA–I HLA–II), lipid–presenting molecules (CD1b CD1c), factors T–cell activation (CD40 CD80). Exposure to cytokines markedly up–regulates these molecules. Importantly, freshly isolated from...
The interaction of mitochondria with proapoptotic proteins activates apoptosis pathways. Previous findings have identified ganglioside GD3 (GD3) as an emerging apoptotic lipid intermediate that targets in response to death signals. Using immunoelectron and laser scanning confocal microscopy, we characterize the trafficking tumor necrosis factor-α (TNF-α) rat hepatocytes. In control hepatocytes, is present predominantly at plasma membrane well endosomal/Golgi network, verified by its...
Abstract CD6 is a cell surface receptor expressed on immature thymocytes and mature T B1a lymphocytes. The ultimate function of has not been deciphered yet, but much evidence supports role for in activation differentiation. In this study, we show that fraction molecules physically associates with the TCR/CD3 complex by coimmunoprecipitation, cocapping, fluorescence resonance energy transfer experiments. Image analysis Ag-specific T-APC conjugates demonstrated its ligand, activated leukocyte...
Ras proteins are small guanosine triphosphatases involved in the regulation of important cellular functions such as proliferation, differentiation, and apoptosis. Understanding intracellular trafficking is crucial to identify novel signaling platforms. In this study, we report that epidermal growth factor triggers Kirsten (KRas) translocation onto endosomal membranes (independently calmodulin protein kinase C phosphorylation) through a clathrin-dependent pathway. From early endosomes, KRas...
Annexin A6 (AnxA6) belongs to a family of Ca 2+ ‐dependent membrane‐binding proteins and is involved in the regulation endocytic exocytic pathways. We previously demonstrated that AnxA6 regulates receptor‐mediated endocytosis lysosomal targeting low‐density lipoproteins translocates cholesterol‐enriched late endosomes (LE). As cholesterol modulates membrane binding cellular location AnxA6, but also affects intracellular distribution caveolin, we investigated localization trafficking caveolin...
Abstract Caveolin-1 (CAV1) is a structural protein of caveolae involved in lipid homeostasis and endocytosis. Using newly generated pure Balb/C CAV1 null (Balb/CCAV1−/−) mice, CAV1−/− mice from Jackson Laboratories (JAXCAV1−/−), developed the Kurzchalia Laboratory (KCAV1−/−), we show that under physiological conditions expression mouse tissues necessary to guarantee an efficient progression liver regeneration survival after partial hepatectomy. Absence compensated by development...