A5005243390- Ion Channels and Receptors
- Ion channel regulation and function
- Calcium signaling and nucleotide metabolism
- Mast cells and histamine
- Asthma and respiratory diseases
- Magnesium in Health and Disease
- Biochemical Analysis and Sensing Techniques
- Olfactory and Sensory Function Studies
- Cardiac electrophysiology and arrhythmias
- Neurobiology and Insect Physiology Research
- Adipose Tissue and Metabolism
- Connexins and lens biology
- Cellular transport and secretion
- Polyamine Metabolism and Applications
- Pancreatic function and diabetes
- Adenosine and Purinergic Signaling
- Sirtuins and Resveratrol in Medicine
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Respiratory and Cough-Related Research
- interferon and immune responses
- Urinary Bladder and Prostate Research
- Inflammasome and immune disorders
- melanin and skin pigmentation
- Plant Stress Responses and Tolerance
- Genetics, Aging, and Longevity in Model Organisms
German Centre for Cardiovascular Research
2020-2024
Heidelberg University
2012-2024
University Hospital Heidelberg
2012-2019
Institute of Pharmacology
2018
Universitätsklinikum des Saarlandes
2012
Saarland University
2007-2011
Bogomoletz Institute of Physiology
2003-2004
National Academy of Sciences of Ukraine
2003
Inflammation-induced neurodegeneration is a defining feature of multiple sclerosis (MS), yet the underlying mechanisms remain unclear. By dissecting neuronal inflammatory stress response, we discovered that neurons in MS and its mouse model induce stimulator interferon genes (STING). However, activation STING requires detachment from stromal interaction molecule 1 (STIM1), process triggered by glutamate excitotoxicity. This initiates non-canonical signaling, which leads to autophagic...
Full-length transient receptor potential (TRP) cation channel TRPC4alpha and shorter TRPC4beta lacking 84 amino acids in the cytosolic C terminus are expressed smooth muscle endothelial cells where they regulate membrane Ca(2+) influx. In common with other "classical" TRPCs, TRPC4 is activated by G(q)/phospholipase C-coupled receptors, but underlying mechanism remains elusive. Little also known about any isoform-specific regulation. Here we show that not was strongly inhibited...
Production of functional spermatozoa requires regulation the Ca 2+ concentration in epididymal fluid by TRPV6.
Mast cells (MCs), which are best known for their detrimental role in patients with allergic diseases, act a diverse array of physiologic and pathologic functions made possible by the plurality MC types. Their various developmental avenues distinct sensitivity to (micro-) environmental conditions convey extensive heterogeneity, resulting functions. We briefly summarize this elaborate on molecular determinants that allow MCs communicate environment fulfill tasks, discuss protease repertoire...
Transient receptor potential (TRP) proteins form cation channels that are regulated through strikingly diverse mechanisms including multiple cell surface receptors, changes in temperature, pH and osmolarity, cytosolic free Ca(2+) concentration ([Ca(2+)](i)), by phosphoinositides which makes them polymodal sensors for fine tuning of many cellular systemic processes the body. The 28 TRP identified mammals classified into six subfamilies: TRPC, TRPV, TRPM, TRPA, TRPML, TRPP. When activated,...
Regulated exocytosis is initiated by increased Ca2+ concentrations in close spatial proximity to secretory granules, which effectively prevented when the cell at rest. Here we showed that of zymogen granules acinar cells was driven directly released from acidic stores including through NAADP-activated two-pore channels (TPCs). We identified OCaR1 (encoded Tmem63a) as an organellar regulator protein integral membrane controlled release via inhibition TPC1 and TPC2 currents. Deletion led...
Significance The worldwide prevalence of allergic and anaphylactic reactions has increased massively over recent decades. Mast cells basophils are essential drivers these diseases, releasing inflammatory mediators such as histamine. Here, we link the endolysosomal two-pore channel TPC1 to systemic anaphylaxis in vivo underlying mast cell function ex vivo. TPC1-deficient mice develop enhanced reflected by a drop body temperature slower recovery compared wild-type animals. Genetic deletion or...
Upon stimulation of membrane receptors, nicotinic acid adenine dinucleotide phosphate (NAADP) is formed as second messenger within seconds and evokes Ca
The activation of mast cells (MC) is part the innate and adaptive immune responses depends on Ca2+ entry across plasma membrane, leading to release preformed inflammatory mediators by degranulation or de novo synthesis. calcium conducting channels TRPV family, known their thermo osmotic sensitivity, have been proposed be involved in MC murine, rat, human cell models. So far, immortalized lines nonspecific blockers employed characterize role MC. aim this work was elucidate physiological using...
Animals need to sense and react potentially dangerous environments. TRP ion channels participate in nociception, presumably via Ca(2+) influx, most animal species. However, the relationship between permeation animals' nocifensive behaviour is unknown. Here we use an invertebrate model with relevance for mammalian pain. We analyse putative selectivity filter of OSM-9, a TRPV channel, osmotic avoidance Caenorhabditis elegans. Using mutagenized OSM-9 expressed head nociceptor neuron, ASH, study...
Blood-brain barrier (BBB) dysfunction is critically involved in determining the extent of several central nervous systems (CNS) pathologies and here particular neuroinflammatory conditions. Inhibiting BBB breakdown could reduce level vasogenic edema number immune cells invading CNS, thereby counteracting neuronal injury. Transient receptor potential (TRP) channels have an important role as environmental sensors constitute attractive therapeutic targets that are calcium homeostasis during...
Mast cells are a heterogeneous group of immune cells. The simplest and commonly accepted classification divides them in two groups according to their protease content. We have compared the action diverse secretagogues on bone marrow derived (BMMC) peritoneal (PMC) mast which represent classical models mucosal connective tissue type mice. Whereas antigen stimulation FcεRI receptors was similarly effective triggering elevations free intracellular Ca2+ concentration ([Ca2+]i) both BMMC PMC,...
Abstract TRPM4 proteins form Ca 2+ -activated non selective cation (CAN) channels that affect transmembrane -influx by determining the membrane potential. Tight control of intracellular concentration is essential for mast cell responses. In this study, we analyzed expression in peritoneal cells (PCMC) as a model connective tissue type with respect to FcεRI-evoked calcium changes and subcellular localization fluorescently labeled using two viral transduction systems before following antigen...
Nicotinic acid adenine dinucleotide phosphate (NAADP) is a second messenger that evokes calcium release from intracellular organelles by the engagement of channels, including members Transient Receptor Potential (TRP) family, such as TRPML1, (structurally) related Two Pore Channel type 1 (TPC1) and TPC2 channels well Ryanodine Receptors (RYR1) (Guse, 2012). NAADP acidic stores many cell types 2012), NAADP-sensitive Ca2+ have been described in hippocampal neurons rat (Bak et al., 1999;...
Early embryogenesis depends on proper control of intracellular homeostasis ions including Ca2+ and Mg2+. Deletion the Mg2+ conducting TRPM7 channel is embryonically lethal in mice but leaves compaction, blastomere polarization, blastocoel formation, correct specification lineages trophectoderm inner cell mass unaltered despite that free cytoplasmic reduced at two-cell stage. Although Trpm7-/- embryos are able to hatch from zona pellucida, no expansion trophoblast cells can be observed, not...
Mast cells (MCs), as a part of the immune system, play key role in defending host against several pathogens and initiation allergic response.The activation MCs via cross-linking surface IgE bound to high affinity receptor (FcεRI), well through stimulation other receptors, initiates rise free intracellular Ca 2+ level ([Ca ] i ) that promotes release inflammatory mediators.The identification molecular constituents involved these signaling pathways is crucial for understanding regulation MC...