A5006713418- Neuroscience and Neuropharmacology Research
- Neural dynamics and brain function
- Lipid Membrane Structure and Behavior
- Cellular transport and secretion
- Photoreceptor and optogenetics research
- Ion channel regulation and function
- Advanced Fluorescence Microscopy Techniques
- Neurological diseases and metabolism
- Mitochondrial Function and Pathology
- Neurogenetic and Muscular Disorders Research
- Growth Hormone and Insulin-like Growth Factors
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Advanced Memory and Neural Computing
- Neuroblastoma Research and Treatments
- RNA regulation and disease
- Cell Image Analysis Techniques
- Animal Genetics and Reproduction
- Microbial infections and disease research
- Herpesvirus Infections and Treatments
- Genetics and Neurodevelopmental Disorders
- Advanced Electron Microscopy Techniques and Applications
- Ubiquitin and proteasome pathways
- Virus-based gene therapy research
- Animal Virus Infections Studies
Radboud University Nijmegen
2023-2025
University Hospital Heidelberg
2022
Heidelberg University
2022
Max Planck Institute for Brain Research
2016-2020
Max Planck Society
2020
Université de Bordeaux
2012-2019
Institut Interdisciplinaire de Neuroscience
2012-2016
Centre National de la Recherche Scientifique
2015
Harvard University
2013
Maccabi Health Care Services
2009
Local translation in presynaptic terminals Proteins carry out most of the functions cells, including neurons, which are one morphologically complex cell types body. This poses challenges for how proteins can be supplied to remote regions where connections (synapses) made with other neurons. One solution neuron protein-supply problem involves local synthesis from messenger RNA (mRNA) molecules located at or near synapses. Hafner et al. used sequencing methods and superresolution microscopy...
Short-term plasticity of AMPAR currents during high-frequency stimulation depends not only on presynaptic transmitter release and postsynaptic recovery from desensitization, but also fast diffusion. How diffusion within the synapse regulates synaptic transmission millisecond scale remains mysterious. Using single-molecule tracking, we found that, upon glutamate binding, diffuse faster. stabilized in different conformational states by point mutations pharmacology, show that desensitized...
N-glycosylation – the sequential addition of complex sugars to adhesion proteins, neurotransmitter receptors, ion channels and secreted trophic factors as they progress through endoplasmic reticulum Golgi apparatus is one most frequent protein modifications. In mammals, organ-specific events occur in brain. Yet, little known about nature, function regulation neurons. Using imaging, quantitative immunoblotting mass spectrometry, we show that hundreds neuronal surface membrane proteins are...
Trafficking and biophysical properties of AMPA receptors (AMPARs) in the brain depend on interactions with associated proteins. We identify Shisa6, a single transmembrane protein, as stable directly interacting bona fide AMPAR auxiliary subunit. Shisa6 is enriched at hippocampal postsynaptic membranes co-localizes AMPARs. The C-terminus harbours PDZ domain ligand that binds to PSD-95, constraining mobility AMPARs plasma membrane confining them densities. expressed HEK293 cells alters GluA1-...
The plasticity of excitatory synapses is an essential brain process involved in cognitive functions, and dysfunctions such adaptations have been linked to psychiatric disorders as depression. Although the intracellular cascades that are altered models depression stress-related under considerable scrutiny, molecular interplay between antidepressants glutamatergic signaling remains elusive. Using a combination electrophysiological single nanoparticle tracking approaches, we here report...
Changes in the efficacies of synapses are thought to be neurobiological basis learning and memory. The efficacy a synapse depends on its current number neurotransmitter receptors. Recent experiments have shown that these receptors highly dynamic, moving back forth between time scales seconds minutes. This suggests spontaneous fluctuations synaptic competition nearby for available Here we propose mathematical model this from local dendritic pool. Using minimal assumptions, produces fast...
Mucopolysaccharidosis VI (MPS VI) is a lysosomal storage disease with autosomal recessive inheritance caused by deficiency of the enzyme arylsulfatase B (ASB), which involved in degradation dermatan sulfate and chondroitin 4-sulfate. A MPS mouse model was generated targeted disruption ASB gene. Homozygous mutant animals exhibit elevated urinary secretion sulfate. They develop progressive symptoms resembling those humans. Around 4 weeks age facial dysmorphia becomes overt, long bones are...
Human cortical malformations, including lissencephaly, polymicrogyria and other diseases of neurodevelopment, have been associated with mutations in microtubule subunits microtubule-associated proteins. Here we report our cloning the brain dimple (brdp) mouse mutation, which recovered from an ENU screen for recessive perinatal phenotypes affecting neurodevelopment. We identify causal mutation tubulin, beta-2b (Tubb2b) gene as a missense at highly conserved residue (N247S). Brdp/brdp...
In the brain, strength of each individual synapse is defined by complement proteins present or "local proteome." Activity-dependent changes in synaptic are result this local proteome and posttranslational protein modifications. Although most have been identified, we still know little about copy numbers synapses variations between synapses. We use DNA-point accumulation for imaging nanoscale topography as a single-molecule super-resolution technique to visualize quantify single The provides...
Abstract AMPA-type glutamate receptors (AMPARs) underlie most of the excitatory synaptic transmission in brain and are crucial for implementing long-term plasticity. AMPARs multi-protein complexes composed two types subunits: pore-forming subunits GluA1-4 that assemble endoplasmic reticulum form glutamate-gated ion channel, auxiliary modulate receptor bio-physical properties mediate their forward trafficking to plasma membrane. Here, using a combination theoretical experimental approaches,...
Across their dendritic trees, neurons distribute thousands of protein species that are necessary for maintaining synaptic function and plasticity need to be produced continuously trafficked final destination. As each branchpoint splits the flow, increasing branchpoints decreases total number downstream. Consequently, a neuron needs produce more proteins maintain minimal at distal synapses. Combining in vitro experiments theoretical framework, we show diffuse within cell plasma membrane are,...
The present study describes the application of egg yolk antibodies in immunohistochemistry. In order to obtain specific against canine distemper virus (CDV), chickens were immunized with attenuated virus. Distinct antibody titres serum and could be detected by means a modified plaque/focus immunoassay (ELISA) two weeks after second immunization. lower concentrations corresponding globulin preparations are attributed loss caused isolation procedure (dextran ammonium sulfate precipitation)....
We describe the production of polyclonal chicken antibodies specific for bovine growth hormone (bGH) and prolactin (PRL). Antibodies were generated by immunization laying hens with recombinant bGH (rbGH), pituitary derived (pbGH), ovine PRL (oPRL). After lipoprotein fraction was removed dextran sulfate precipitation isolated from egg yolks ammonium precipitation. Immunization rbGH oPRL large amounts antibodies, as revealed ELISA Western blot analysis. against pbGH showed pronounced...
An eight‐year‐old intact male Bernese mountain dog was referred with a history of chronic vomiting, coughing and signs respiratory distress. Other historical findings included lethargy, weight loss choking. On presentation, clinical were Horner's syndrome, ipsilateral laryngeal hemiplegia, coughing, gagging, distress vomiting. Lateral cervical radiographs showed ill‐defined mineralisation in the soft tissue ventral to third vertebra, while ultrasonography neck revealed well marginated...
Abstract There is ample evidence for localized mRNAs and protein synthesis in neuronal dendrites, however, demonstrations of these processes presynaptic terminals are limited. We used expansion microscopy to resolve pre- postsynaptic compartments brain slices. Most the hippocampus forebrain contained mRNA ribosomes. sorted fluorescently labeled synaptosomes from mouse then sequenced hundreds species present within excitatory boutons. After brief metabolic labeling, more them 30% all...