A5024028915- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Ion channel regulation and function
- Nicotinic Acetylcholine Receptors Study
- Chemical Synthesis and Analysis
- Molecular Sensors and Ion Detection
- Genetics and Neurodevelopmental Disorders
- Photoreceptor and optogenetics research
- Adenosine and Purinergic Signaling
- Genomics and Rare Diseases
- Epilepsy research and treatment
- Amino Acid Enzymes and Metabolism
- Neuroendocrine regulation and behavior
- Photochromic and Fluorescence Chemistry
- Fuel Cells and Related Materials
- Neuropeptides and Animal Physiology
- Neurobiology and Insect Physiology Research
- Nanopore and Nanochannel Transport Studies
- Alzheimer's disease research and treatments
- HIV Research and Treatment
- MicroRNA in disease regulation
- RNA and protein synthesis mechanisms
- Lipid Membrane Structure and Behavior
- Neuroinflammation and Neurodegeneration Mechanisms
- Genomic variations and chromosomal abnormalities
Technical University of Darmstadt
2014-2024
Max Planck Institute for Brain Research
2002-2016
Neurology, Inc
2016
Max Planck Society
1999-2009
RIKEN Center for Brain Science
2009
Goethe University Frankfurt
1992-2003
Centre National de la Recherche Scientifique
1999
École Polytechnique Fédérale de Lausanne
1998
The amino acids L-glutamate and glycine are essential agonists of the excitatory NMDA receptor, a subtype ionotropic glutamate receptor family. native is composed two types homologous membrane-spanning subunits, NR1 NR2. Here, numbers glycine-binding glutamate-binding NR2 subunits in hetero-oligomer were determined by coexpressing wild-type (wt) with low-affinity mutant NR1(Q387K), wt NR2B NR2BE387A, Xenopus oocytes. In both cases, analysis resulting dose-response curves revealed three...
NMDA receptors require both L-glutamate and the coagonist glycine for efficient channel activation. The binding site of these heteromeric receptor proteins is formed by regions NMDAR1 (NR1) subunit that display sequence similarity to bacterial amino acid proteins. Here, we demonstrate glutamate located on homologous NR2B subunit. Mutation residues within N-terminal domain loop region between membrane segments M3 M4 significantly reduced efficacy glutamate, but not glycine, in gating. Some...
The tubulin-binding protein gephyrin, which anchors the inhibitory glycine receptor (GlyR) at postsynaptic sites, decorates GABAergic membranes in various brain regions, and gephyrin clusters are absent from cortical cultures of mice deficient for GABA A γ2 subunit. Here, we investigated clustering receptors knock-out ( geph −/−) mice. Both sections cultured hippocampal neurons derived −/− mice, synaptic containing either or α2 subunit were absent, whereas glutamate subunits normally...
<h3>Background</h3> We aimed for a comprehensive delineation of genetic, functional and phenotypic aspects <i>GRIN2B</i> encephalopathy explored potential prospects personalised medicine. <h3>Methods</h3> Data 48 individuals with de novo variants were collected from several diagnostic research cohorts, as well 43 patients the literature. Functional consequences response to memantine treatment investigated in vitro eventually translated into patient care. <h3>Results</h3> Overall, 86...
To determine the phenotypic spectrum caused by mutations in GRIN1 encoding NMDA receptor subunit GluN1 and to investigate their underlying functional pathophysiology.We collected molecular clinical data from several diagnostic research cohorts. Functional consequences of were investigated Xenopus laevis oocytes.We identified heterozygous de novo 14 individuals reviewed phenotypes all 9 previously reported patients. These 23 presented with a distinct phenotype profound developmental delay,...
porter 1 (GlyT1).GlyT1 Ϫ/Ϫ mice die on the first postnatal Deutschordenstrasse 46 day, due to severe motor and respiratory deficits re-60528 Frankfurt sulting from overinhibition (Gomeza et al., 2003 [this issue Germany of Neuron]).Here, we describe a mouse line that lacks 2 Department Neuro-and Sensory Physiology functional glycine transporter (GlyT2), neuronal University Go ¨ttingen GlyT isoform localized in presynaptic terminals gly-Humboldtallee 23 cinergic interneurons (Zafra, 1995a;...
The N-methyl-D-aspartate (NMDA) subtype of ionotropic glutamate receptors is a heterooligomeric membrane protein composed homologous subunits. Here, the contribution M3-M4 loop NR1 subunit to binding and co-agonist glycine was investigated by site-directed mutagenesis. Substitution phenylalanine residues at positions 735 or 736 produced 15- 30-fold reduction in apparent affinity without affecting competitive antagonist 7-chlorokynurenic acid; mutation both caused >100-fold decrease...
Objective To identify novel epilepsy genes using a panel approach and describe the functional consequences of mutations. Methods Using approach, we screened 357 patients comprising vast spectrum epileptic disorders for defects in known to contribute and/or intellectual disability (ID). After detection mutations gene, investigated effects Xenopus laevis oocytes follow‐up cohort. Results We revealed de novo GRIN2B encoding NR2B subunit N‐methyl‐D‐aspartate (NMDA) receptor 2 individuals with...
1. The effect of the divalent cation Zn2+ on inhibitory glycine receptor (GlyR) currents was investigated in rat embryonic spinal cord neurons and Xenopus oocytes expressing recombinant GlyRs. 2. In cultured neurons, potentiated glycine-induced whole-cell about 3-fold when applied extracellularly at concentrations 0.5-10 microM. contrast, higher (> 100 microM) decreased response. 3. A similar biphasic modulation by also found with homo- hetero-oligomeric GlyRs generated oocytes....
Here we describe a novel purinergic receptor, the P2X5 cloned from rat heart. The full-length cDNA encodes protein 455 amino acids long which shares an overall identity of 40-47% with other members P2X receptor family. mRNA transcripts are found predominantly in heart but also present brain, spinal cord and adrenal gland. Functional expression recombinant HEK-293 cells shows current that resembles mostly P2X2 phenotype: ATP-activated reveals little agonist desensitization, is not activated...
Zn2+ is thought to modulate neurotransmission by affecting currents mediated ligand-gated ion channels and transmitter reuptake Na+-dependent transporter systems. Here, we examined the in vivo relevance of neuromodulation producing knockin mice carrying mutation D80A glycine receptor (GlyR) α1 subunit gene (Glra1). This substitution selectively eliminates potentiating effect on GlyR currents. Mice homozygous for Glra1(D80A) develop a severe neuromotor phenotype postnatally that resembles...
Article16 April 2018free access Source DataTransparent process Distinct in vivo roles of secreted APP ectodomain variants APPsα and APPsβ regulation spine density, synaptic plasticity, cognition Max C Richter Institute Pharmacy Molecular Biotechnology (IPMB), Ruprecht-Karls University Heidelberg, Germany Search for more papers by this author Susann Ludewig Zoological Institute, Division Cellular Neurobiology, TU Braunschweig, Alex Winschel Department Biology, Neurophysiology und Neurosensory...
1. The effects of Zn2+ on glycine receptor (GlyR) currents were analysed in Xenopus oocytes and human embryonic kidney cells expressing homomeric wild-type mutant alpha1 subunit GlyRs. 2. Low concentrations (10 microM) extracellular converted the partial agonist taurine into a high-efficacy agonist. Concentration-response analysis showed that EC50 for decreased whereas Hill coefficient increased under these conditions. In contrast, 50-500 microM an value reduced maximal inducible currents....
The neuronal glycine receptor is a ligand-gated chloride channel composed of ligand binding alpha and structural beta polypeptides. Homology screening human fetal brain cDNA library resulted in the identification two alternative splice variants alpha3 subunit. amino acid sequence predicted for alpha3L variant was largely identical to corresponding rat In contrast, novel alpha3K lacked coding 15 acids located within cytoplasmic loop connecting transmembrane spanning region 3 (TM3) TM4. Using...
N-Methyl-d-aspartate (NMDA) receptors are tetrameric protein complexes composed of the glycine-binding NR1 subunit with a glutamate-binding NR2 and/or NR3 subunit. Tri-heteromeric containing NR1, NR2, and subunits reconstitute channels, which differ strikingly in many properties from respective glycine- glutamate-gated NR1/NR2 NR1/NR3 gated by glycine alone. Therefore, an accurate oligomerization process different has to assure proper NMDA receptor assembly, been assumed occur via...