A5029441793- Neuroscience and Neuropharmacology Research
- Respiratory Support and Mechanisms
- Lipid Membrane Structure and Behavior
- Neuroinflammation and Neurodegeneration Mechanisms
- Nicotinic Acetylcholine Receptors Study
- Receptor Mechanisms and Signaling
- Photoreceptor and optogenetics research
- Cancer, Hypoxia, and Metabolism
- Pregnancy-related medical research
- Cardiac Ischemia and Reperfusion
- Nitric Oxide and Endothelin Effects
- Preterm Birth and Chorioamnionitis
- Cardiac Arrest and Resuscitation
- Ion channel regulation and function
- Mechanical Circulatory Support Devices
- Tryptophan and brain disorders
- Photochromic and Fluorescence Chemistry
- Anesthesia and Neurotoxicity Research
- Cellular transport and secretion
- Food Allergy and Anaphylaxis Research
- Enhanced Recovery After Surgery
- Extracellular vesicles in disease
- Intensive Care Unit Cognitive Disorders
- Molecular Sensors and Ion Detection
- Neural dynamics and brain function
Medical University of Vienna
2015-2025
Pain and Rehabilitation Medicine
2019-2020
Barmherzige Schwestern Krankenhaus Wien
2019
Ludwig Boltzmann Cluster for Cardiovascular Research
2017
Union Hospital
2017
Vienna General Hospital
2013
University of Vienna
2001-2012
University College London
2004-2009
University of Pennsylvania
2004-2008
University of Göttingen
2004
γ-Aminobutyric acid (GABA) type A receptors mediate fast inhibitory synaptic transmission and have been implicated in responses to sedative/hypnotic agents (including neuroactive steroids), anxiety, learning memory. Using gene targeting technology, we generated a strain of mice deficient the δ subunit GABA receptors. In vivo testing various behavioral revealed strikingly selective attenuation steroids, but not other modulatory drugs. Electrophysiological recordings from hippocampal slices...
GABAA receptors are ligand-gated chloride ion channels that presumed to be pentamers composed of alpha, beta, and gamma subunits. The subunit stoichiometry, however, is controversial, the arrangement presently not known. In this study ratio subunits in recombinant alpha1beta3gamma2 was determined Western blots from relative signal intensities antibodies directed against N terminus or cytoplasmic loop different after reactivity these had been with receptor chimeras N-terminal domain one...
The ability of peptide‐ N 4 ‐( ‐acetyl‐β‐glucosaminyl)asparagine amidase F (PNGase F) from Flavobacterium meningosepticum and PNGase A sweet almonds to deglycosylate N‐glycopeptides N‐glycoproteins plants was compared. Bromelain glycopeptide horseradish peroxidase‐C glycoprotein, which contain xylose linked β1 → 2 β‐mannose fucose α1 3 the innermost ‐acetylglucosamine, were used as substrates. In contrast A, enzyme F. did not act upon these substrates even at concentrations 100‐fold higher...
Classical benzodiazepine sensitive GABA A receptor subtypes, the major mediators of fast synaptic inhibition in brain are heteropentamers that can be assembled from α1–3/5, β1–3, and γ2 subunits, but how neurons orchestrate their selective accumulation at synapses remains obscure. We have identified a 10 amino acid hydrophobic motif within intracellular domain α2 subunit regulates receptors inhibitory sites on both axon initial segments dendrites mechanism dependent scaffold protein...
γ-Aminobutyric acid type A receptors (GABA Rs) are the major sites of fast synaptic inhibition in brain. An essential determinant for efficacy is regulation GABA R cell surface stability. Here, we have examined endocytic sorting, a critical regulator receptor number. In neurons, rapid constitutive endocytosis Rs was evident. Internalized were then either rapidly recycled back to surface, or on slower time scale, targeted lysosomal degradation. This sorting decision regulated by direct...
The N‐linked carbohydrate chains of phospholipase A 2 from honeybee ( Apis mellifera ) were released glycopeptides with peptide‐ N ‐glycanase and reductively aminated 2‐aminopyridine. fluorescent derivatives separated by size‐fractionation reverse‐phase HPLC, yielding 14 fractions. Structural analysis was accomplished compositional methylation analyses, comparison the HPLC elution patterns reference oligosaccharides, stepwise exoglycosidase digestions which monitored and, where necessary,...
The reactivity of sera from honeybee venom allergic patients with the N-glycan phospholipase A2 was investigated using neoglycoproteins an enzyme-linked immunosorbent assay. Of 122 appreciable levels IgE antibodies directed against bee as measured by radioallergosorbent test, 34 exhibited significant amounts glycan-reactive IgE. These cross-reacted plant glycoprotein bromelain. interaction could be inhibited glycopeptides bromelain which shares α1,3-fucosylation asparagine-bound...
The majority of fast synaptic inhibition in the brain is mediated by benzodiazepine-sensitive α1-subunit-containing GABA type A receptors (GABA Rs); however, our knowledge mechanisms neurons use to regulate their accumulation rudimentary. Using immunoprecipitation, we demonstrate that Rs and gephyrin are intimately associated at inhibitory synapses cultured rat neurons. In vitro reveal E-domain directly binds α1 subunit with an affinity ∼20 μ m , residues 360–375 within intracellular domain...
GABAA receptors are clustered at synaptic sites to achieve a high density of postsynaptic opposite the input axonal terminals. This allows an efficient propagation GABA mediated signals, which mostly result in neuronal inhibition. A key organizer for inhibitory is 93 kDa protein gephyrin that forms oligomeric superstructures beneath area. Gephyrin has long been known be directly associated with glycine receptor β subunits mediate inhibition spinal cord. Recently, have also shown interact...
In cerebellum, GABA A receptors containing α 6 subunits are expressed exclusively in granule cells. The number of receptor subtypes formed these cells and their subunit composition presently not known. Immunoaffinity chromatography on subunit-specific antibodies indicated that 45% cerebellar extracts contained subunits. Western blot analysis demonstrated 1 , β 2 3 γ δ co-purified with subunits, suggesting the existence multiple subtypes. These were identified using a new method based...
The regulation of the number gamma2-subunit-containing GABA(A) receptors (GABA(A)Rs) present at synapses is critical for correct synaptic inhibition and animal behavior. This occurs, in part, by controlled removal from membrane clathrin-coated vesicles, but it remains unclear how clathrin recruitment to surface GABA(A)Rs regulated. Here, we identify a gamma2-subunit-specific Yxxvarphi-type-binding motif adaptor protein, AP2, which located within site gamma2-subunit tyrosine phosphorylation....
The multifunctional scaffolding protein gephyrin is a key player in the formation of postsynaptic scaffold at inhibitory synapses, clustering both glycine receptors (GlyRs) and selected GABA(A) receptor (GABA(A)R) subtypes. We report direct interaction between GABA(A)R α3 subunit gephyrin, mapping reciprocal binding sites using mutagenesis, overlay, yeast two-hybrid assays. This analysis reveals that critical determinants this are located motif FNIVGTTYPI M3-M4 domain SMDKAFITVL N terminus E...
Gephyrin is the major protein determinant for clustering of inhibitory neurotransmitter receptors. Earlier analyses revealed that gephyrin tightly binds to residues 398-410 glycine receptor β subunit (GlyR β) and, as demonstrated only recently, also interacts with GABA(A) receptors (GABA(A)Rs) containing α1, α2, and α3 subunits. Here, we dissect molecular basis underlying interactions between GABA(A)Rs these α-subunits compare them crystal structure gephyrin-GlyR complex. Biophysical...
Abstract Any given subunit of the heteromultimeric type‐A γ‐aminobutyric acid (GABA) GABA A receptor may be present in several subtypes expressed by individual neurons. Changes expression a result differential changes other subunits depending on composition subtype, leading to alterations neuronal responsiveness GABA. We used targeted disruption α6 gene test for subunits. Immunoprecipitation and ligand binding experiments indicated that receptors were reduced ≈ 50% cerebellum –/– mice....
Using a novel antibody directed against the alpha4 subunit of gamma-aminobutyric acidA (GABAA) receptors, 5% all [3H]muscimol but only about 2% [3H]Ro15-4513 binding sites present in brain membrane extracts could be precipitated. This indicated that part receptors containing did not contain sites. Immunoaffinity purification and Western blot analysis demonstrated alpha1, alpha2, alpha3, beta1, beta2, beta3 subunits also gamma1, gamma2, gamma3, delta can colocalized with native GABAA...
GABAA receptors are chloride channels composed of five subunits. Cerebellar granule cells express abundantly six subunits belonging to four subunit classes. These assembled into a number distinct receptors, but the regulation their relative proportions is yet unknown. Here, we studied composition cerebellar after targeted disruption δ gene. In membranes and extracts δ−/− cerebellum, [3H]muscimol binding was not significantly changed, whereas [3H]Ro15-4513 increased by 52% due an increase in...
Abstract In cerebellum, 13 different GABA A receptor subunits are expressed. The number of subtypes formed in this tissue, their subunit composition and quantitative importance so far has not been determined. the present study, immunodepletion by immunoaffinity chromatography, as well immunoprecipitation western blot analysis was performed using subunit‐specific antibodies to provide an overview on abundance mouse rat cerebellum. Results obtained indicate that α 1 β x γ 2 , 6 δ major...
In Brief BACKGROUND: Intermittent hypoxia may occur in a number of clinical scenarios, including interruption myocardial blood flow or breathing disorders such as obstructive sleep apnea. Although intermittent has been linked to cardiovascular and cerebrovascular disease, the effect on human heart is not fully understood. Therefore, present study, we compared cellular responses cultured adult cardiac myocytes (HACMs) exposed different conditions continuous normoxia. METHODS: HACMs were...
Drug development for human disease relies on preclinical model systems such as cell cultures and animal experiments before therapeutic treatments can ultimately be tested humans in clinical studies. We here describe the generation of a novel line (HLMVEC/SVTERT289) that we generated by transfection microvascular endothelial cells from healthy donor lung tissue with catalytic domain telomerase SV40 large T/small t-antigen. These exhibited satisfactory growth characteristics largely maintained...
Abstract Background Acute respiratory distress syndrome (ARDS) associated with coronavirus infectious disease (COVID)-19 has been a challenge in intensive care medicine for the past three years. Dysregulation of renin–angiotensin system (RAS) is linked to COVID-19, but also non-COVID-19 ARDS. It still unclear whether changes RAS are prognosis severe COVID-19. Methods In this prospective exploratory study, blood samples 94 patients COVID-19 were taken within 48 h admission medical ward or an...
Fast synaptic inhibition in the brain is largely mediated by gamma-aminobutyric acid receptors (GABA(A)R). While pharmacological manipulation of GABA(A)R function therapeutic agents, such as benzodiazepines can have profound effects on neuronal excitation and behavior, endogenous mechanisms neurons use to regulate efficacy their impact behavior remains poorly understood. To address this issue, we created a knock-in mouse which tyrosine phosphorylation GABA(A)Rs gamma2 subunit,...