A5086603873- Neuroscience and Neuropharmacology Research
- Cellular transport and secretion
- Ion channel regulation and function
- Photoreceptor and optogenetics research
- Lipid Membrane Structure and Behavior
- Retinal Development and Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Neural dynamics and brain function
- Connexins and lens biology
- Nicotinic Acetylcholine Receptors Study
- Neurobiology and Insect Physiology Research
- Innovations in Medical Education
- Genetics and Neurodevelopmental Disorders
- Hippo pathway signaling and YAP/TAZ
- S100 Proteins and Annexins
- Genetic Neurodegenerative Diseases
- Signaling Pathways in Disease
- Receptor Mechanisms and Signaling
- Renal Diseases and Glomerulopathies
- Autism Spectrum Disorder Research
- Neurogenesis and neuroplasticity mechanisms
- Neuropeptides and Animal Physiology
- Virtual Reality Applications and Impacts
- Cellular Mechanics and Interactions
- Neuroscience and Neural Engineering
University of Münster
2015-2024
University of Hong Kong
2023
Heidelberg University
2023
University of Freiburg
2023
Universität Ulm
2023
University Hospital Münster
2022
Stanford University
2016
Blackberry (United States)
2015
University of Göttingen
1992-2007
The University of Texas Southwestern Medical Center
1995-2006
Brain function requires precisely orchestrated connectivity between neurons. Establishment of these connections is believed to require signals secreted from outgrowing axons, followed by synapse formation selected Deletion a single protein, Munc18-1, in mice leads complete loss neurotransmitter secretion synaptic vesicles throughout development. However, this does not prevent normal brain assembly, including layered structures, fiber pathways, and morphologically defined synapses. After...
Chemical synapses are asymmetric intercellular junctions that mediate synaptic transmission. Synaptic organized by trans-synaptic cell adhesion molecules bridging the cleft. not only connect pre- and postsynaptic compartments, but also recognition signaling processes essential for establishment, specification, plasticity of synapses. A growing number include neurexins neuroligins, Ig-domain proteins such as SynCAMs, receptor phosphotyrosine kinases phosphatases, several leucine-rich repeat...
Rett syndrome is a neurodevelopmental disorder caused by mutations in the transcriptional repressor methyl-CpG-binding protein 2 (MeCP2) and represents leading genetic cause for mental retardation girls. MeCP2-mutant mice have been generated to study molecular mechanisms of disease. It was suggested that an imbalance between excitatory inhibitory neurotransmission responsible behavioral abnormalities, although it remained largely unclear which synaptic components are affected how cellular...
CASK is an evolutionarily conserved multidomain protein composed of N-terminal Ca2+/calmodulin-kinase domain, central PDZ and SH3 domains, a C-terminal guanylate kinase domain. Many potential activities for have been suggested, including functions in scaffolding the synapse, organizing ion channels, regulating neuronal gene transcription. To better define physiological importance CASK, we now analyzed "knockdown" mice which expression was suppressed by approximately 70%, knockout (KO) mice,...
Background Copy number variants have emerged as an important genomic cause of common, complex neurodevelopmental disorders. These usually change copy multiple genes, but deletions at 2p16.3, which been associated with autism, schizophrenia and mental retardation, affect only the neurexin 1 gene, alpha isoform. Previous analyses 1α (Nrxn1α) knockout (KO) mouse a model these disorders revealed impairments in synaptic transmission failed to reveal defects social behaviour, one core symptoms...
Astroglial pathology is seen in various neurodegenerative diseases including frontotemporal dementia (FTD), which can be caused by mutations the gene encoding microtubule-associated protein TAU (MAPT). Here, we applied a stem cell model of FTD to examine if astrocytes carry an intrinsic propensity degeneration and determine they induce non-cell-autonomous effects neighboring neurons. We utilized CRISPR/Cas9 genome editing human induced pluripotent (iPS) cell-derived neural progenitor cells...
Neurexins constitute a large family of highly variable cell-surface molecules that may function in synaptic transmission and/or synapse formation. Each the three known neurexin genes encodes two major variants, alpha- and beta-neurexins, are composed distinct extracellular domains linked to identical intracellular sequences. Deletions one, two, or all alpha-neurexins mice recently demonstrated their essential role at synapses. In multiple alpha-neurexin knock-outs, neurotransmitter release...
Neurexins are cell-surface molecules that bind neuroligins to form a heterophilic, Ca(2+)-dependent complex at central synapses. This transsynaptic is required for efficient neurotransmission and involved in the formation of synaptic contacts. In addition, both have been identified as candidate genes autism. Here we performed mutagenesis experiments probe essential components neurexin/neuroligin binding interface single-amino acid level. We found neurexins contact area sharply delineated...
Organization of signalling molecules in biological membranes is crucial for cellular communication. Many receptors, ion channels and cell adhesion are associated with proteins important their trafficking, surface localization or function. These complexes embedded a lipid environment varying composition. Binding affinities stoichiometry such were so far experimentally accessible only isolated systems monolayers culture. Visualization molecular dynamics within correlation to specialized...
Action potential-evoked neurotransmitter release is impaired in knock-out neurons lacking synaptic cell-adhesion molecules α-neurexins (αNrxns), the extracellularly longer variants of three vertebrate Nrxn genes. Ca2+ influx through presynaptic high-voltage gated calcium channels like ubiquitous P/Q-type (CaV2.1) triggers fusion-ready vesicles at many boutons. α2δ Auxiliary subunits regulate trafficking and kinetic properties CaV2.1 pore-forming but it has remained unclear if this involves...
Human genetics has identified rare copy number variations and deleterious mutations for all neurexin genes (NRXN1-3) in patients with neurodevelopmental diseases, electrophysiological recordings animal brains have shown that Nrxns are important synaptic transmission. While several mouse models Nrxn1α inactivation previously been studied behavioral changes, very little information is available other variants. Here, we validate mice lacking Nrxn2α exhibit abnormalities, characterized by social...
Synapses depend on trafficking of key membrane proteins by lateral diffusion from surface populations and exocytosis intracellular pools. The cell adhesion molecule neurexin (Nrxn) plays essential roles in synapses, but the dynamics regulation its are unknown. Here, we performed single-particle tracking live imaging transfected, epitope-tagged Nrxn variants cultured rat mouse wild-type or knock-out neurons. We observed that structurally larger αNrxn molecules more mobile plasma than smaller...
Significance Voltage-gated calcium channels are important regulators of neuronal functions, as for example synaptic transmission. Their auxiliary α 2 δ subunits modulating the currents. Beyond that they have emerged modulators functions. Here, we established a cellular triple knockout/knockdown model in cultured hippocampal neurons by knocking out or down expression all three expressed brain. Our experiments demonstrate presynaptic loss proteins leads to severe defect glutamatergic synapse...
Abstract Multiple trans-synaptic complexes organize synapse development, yet their roles in the mature brain and cooperation remain unclear. We analyzed postsynaptic adhesion protein LRRTM1 prefrontal cortex (PFC), a region relevant to cognition disorders. knockout (KO) mice had fewer synapses, we asked whether other organizers counteract further loss. This determined that immunoglobulin family member SynCAM 1 controls number PFC was upregulated upon Combined deletion substantially lowered...