A5044910212- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Amino Acid Enzymes and Metabolism
- Photoreceptor and optogenetics research
- Genetics and Neurodevelopmental Disorders
- Molecular Sensors and Ion Detection
- Autoimmune Neurological Disorders and Treatments
- Plant and Biological Electrophysiology Studies
- GABA and Rice Research
- Lipid Membrane Structure and Behavior
- Receptor Mechanisms and Signaling
- Neuroscience and Neural Engineering
- Cholinesterase and Neurodegenerative Diseases
- Structural and Chemical Analysis of Organic and Inorganic Compounds
- Nicotinic Acetylcholine Receptors Study
- Gear and Bearing Dynamics Analysis
- Neuroinflammation and Neurodegeneration Mechanisms
- Retinal Development and Disorders
- Electrostatic Discharge in Electronics
- Pharmacological Receptor Mechanisms and Effects
- Digestive system and related health
- Enzyme Structure and Function
- Marine Bivalve and Aquaculture Studies
- Computational Drug Discovery Methods
Ruhr University Bochum
2012-2024
Nanoscale Microscopy and Molecular Physiology of the Brain Cluster of Excellence 171 — DFG Research Center 103
2018
Max Planck Institute of Experimental Medicine
2018
University of Copenhagen
2011-2016
University of Bristol
2008
University of Cologne
2008
Technical University of Munich
2008
Tel Aviv University
2008
University of Utah
2008
Autoantibodies of the IgG class against N-methyl-d-aspartate-receptor subunit NR1 (NMDAR1) were first described in anti-NMDAR encephalitis and seen as disease indicators. Recent work on together over 5000 individuals challenged this exclusive view by showing age-dependently up to >20% NMDAR1-autoantibody seroprevalence with comparable immunoglobulin titer distribution across health disease. The key question therefore is understand properties these autoantibodies, also healthy carriers, order...
Hydrophobic amino acids, rather than glutamate, activate the Arabidopsis glutamate receptor homolog AtGLR1.4.
Autoantibodies of the IgG class against N-methyl-D-aspartate-receptor subunit-NR1 (NMDAR1-AB) were considered pathognomonic for anti-NMDAR encephalitis. This view has been challenged by age-dependent seroprevalence (up to >20%) functional NMDAR1-AB all immunoglobulin classes found in >5000 individuals, healthy or affected different diseases. These findings question a merely encephalitogenic role NMDAR1-AB. Here, we show that belong normal autoimmune repertoire dogs, cats, rats, mice,...
Physical and emotional stress is accompanied by release of hormones such as the glucocorticoid cortisol. This hormone upregulates serum- glucocorticoid-inducible kinase (SGK)1, which in turn stimulates I(Ks), a slow delayed rectifier potassium current that mediates cardiac action potential repolarization. Mutations I(Ks) channel alpha (KCNQ1, KvLQT1, Kv7.1) or beta (KCNE1, IsK, minK) subunits cause long QT syndrome (LQTS), an inherited arrhythmia associated with increased risk sudden death....
Accessory β-subunits of the KCNE gene family modulate function various cation channel α-subunits by formation heteromultimers. Among most dramatic changes biophysical properties a voltage-gated KCNEs are effects KCNE1 on KCNQ1 channels. and believed to form nativeIKs Here, we characterize molecular determinants interaction with channels scanning mutagenesis, double mutant cycle analysis, dynamics simulations. Our findings suggest that binds outer face pore domain, modifies interactions...
The classical tango is a dance characterized by 2/4 or 4/4 rhythm in which the partners coordinated way, allowing dynamic contact. There surprising similarity between and how KCNE β-subunits "dance" to fast of cell with their from Kv channel family. five interact several members channels, thereby modifying gating via interaction single transmembrane-spanning segment, extracellular amino terminus, and/or intracellular carboxy terminus α-subunit. Best studied molecular basis interactions KCNE1...
Abstract The delta receptors, G lu D 1 and 2, are regarded as a subfamily of the ionotropic glutamate receptors solely because sequence homology. While they play important roles in cerebellar function high‐frequency hearing appear to serve structural functions at synapses, ligand‐gated ion channel has not been observed. However, we have previously shown that 2 can form functional channels when grafted with ligand binding domain kainate receptor. In this study, characterized chimera well...
Positive allosteric modulators of 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA)-type ionotropic glutamate receptors are promising compounds for treatment neurological disorders, example, Alzheimer's disease. Here, we report synthesis and pharmacological evaluation a series mono-, di-, or trialkyl-substituted 7-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides, comprising in total 16 new modulators. The trisubstituted 7b, 7d, 7e revealed potent activity (EC2× =...
Circulating autoantibodies (AB) of different immunoglobulin classes (IgM, IgA, and IgG), directed against the obligatory N-methyl-D-aspartate-receptor subunit NR1 (NMDAR1-AB), belong to mammalian autoimmune repertoire, appear with age-dependently high seroprevalence across health disease. Upon access brain, they can exert NMDAR-antagonistic/ketamine-like actions. Still unanswered key questions, addressed here, are conditions NMDAR1-AB formation/boosting, intraindividual persistence/course in...
Inward rectifier potassium channels of the Kir2 subfamily are important determinants electrical activity brain and muscle cells. Genetic mutations in Kir2.1 associate with Andersen-Tawil syndrome (ATS), a familial disorder leading to stress-triggered periodic paralysis ventricular arrhythmia. To identify molecular mechanisms this stress trigger, we analyze Kir channel function localization electrophysiologically by time-resolved confocal microscopy. Furthermore, employ mathematical model...
Herein we describe the first structure–activity relationship study of broad-range iGluR antagonist (2S,3R)-3-(3-carboxyphenyl)pyrrolidine-2-carboxylic acid (1) by exploring pharmacological effect substituents in 4, 4′, or 5′ positions and bioisosteric substitution distal carboxylic for a phosphonic moiety. Of particular interest is hydroxyl group 4′ position 2a which induced preference binding affinity homomeric GluK3 over GluK1 (Ki = 0.87 4.8 μM, respectively). Two X-ray structures ligand...
Abstract The ionotropic glutamate delta receptor GluD1, encoded by the GRID1 gene, is involved in synapse formation, function, and plasticity. GluD1 does not bind glutamate, but instead cerebellin D-serine, which allow formation of trans-synaptic bridges, trigger transmembrane signaling. Despite wide expression nervous system, pathogenic variants have been characterized humans so far. We report homozygous missense five individuals from two unrelated consanguineous families presenting with...
Abstract Ionotropic glutamate receptors (iGluRs) are responsible for most of the fast excitatory communication between neurons in our brain. The GluD2 receptor is a puzzling member iGluR family: It involved synaptic plasticity, plays role human diseases, e.g . ataxia, binds glycine and D-serine with low affinity, yet no ligand has been discovered so far that can activate its ion channel. In this study, we show hinge region connecting two subdomains ligand-binding domain affinity D-serine, by...
Ionotropic glutamate receptors are ligand‐gated ion channels essential for fast excitatory neurotransmission in the brain. In contrast to most other members of iGluR family, subfamily delta receptors, GluD1 and GluD2, does not bind but glycine/D‐serine. is widely expressed brain inner ear, where it required high‐frequency hearing. Furthermore, has been associated with schizophrenia, autism depression. X‐ray structures ligand‐binding domain (LBD) GluD2 have published; however, no...
The stress reaction includes the release of hormones such as cortisol via HPA axis4. One genes regulated by is serum- and glucocorticoid-inducible kinase 1 (SGK1) a stimulator slow outward potassium channels KCNQ1/KCNE1 - one major mediators cardiac repolarization. Apart from KCNE1, several other KCNE subunits including KCNE3 KCNE5 have been detected at mRNA level in tissue well inner ear gastrointestinal tract. Here, we extend our previous investigations to KCNQ1/KCNE3 their modulation...
Investigating subunit assembly of ionotropic glutamate receptor complexes and their trafficking to the plasma membrane under physiological conditions in live cells has been challenging. By confocal imaging fluorescently labeled kainate (KAR) subunits combined with digital co-localization fluorescence resonance energy (FRET) transfer analyses, we investigated homomeric heteromeric identified subcellular location interactions. Our data provide direct evidence for oligomerization KAR as early...
AMPA receptors mediate the majority of fast synaptic transmission in central nervous system and are therefore among most intensively studied ligand-gated ion channels over last decades. However, recent discovery that native receptor complexes contain auxiliary subunits classified as transmembrane regulatory proteins (TARPs) was quite a surprise dramatically changed field research. TARPs regulate trafficking well localization receptors, alter their pharmacological biophysical properties,...