A5013320787- Connexins and lens biology
- Nicotinic Acetylcholine Receptors Study
- Neuroscience and Neuropharmacology Research
- Diabetes Treatment and Management
- Photoreceptor and optogenetics research
- Retinal Development and Disorders
- Diabetes Management and Research
- Diabetes and associated disorders
- Genetics and Neurodevelopmental Disorders
- Hearing, Cochlea, Tinnitus, Genetics
- Ion channel regulation and function
- Biochemical Analysis and Sensing Techniques
- Ion Channels and Receptors
- Ion Transport and Channel Regulation
- Cellular transport and secretion
- Adipose Tissue and Metabolism
- Neurobiology and Insect Physiology Research
- Olfactory and Sensory Function Studies
- Genomics and Chromatin Dynamics
- Congenital heart defects research
- Neuroscience of respiration and sleep
- Biochemical effects in animals
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Autism Spectrum Disorder Research
Saarland University
2016-2025
Rockefeller University
2023
Rockefeller University Press
2023
Howard Hughes Medical Institute
2015-2020
Stanford University
2011-2020
Praxis für Humangenetik
2019
Stanford Medicine
2013-2014
University of Bonn
2000-2012
The University of Texas Southwestern Medical Center
2008
ABSTRACT In order to reveal the biological function(s) of gap-junction protein connexin 45 (Cx45), we generated Cx45-deficient mice with targeted replacement Cx45-coding region lacZ reporter gene. Heterozygous Cx45+/− showed strong expression gene in vascular and visceral smooth muscle cells. embryos exhibited striking abnormalities development died between embryonic day (E) 9.5 10.5. Differentiation positioning endothelial cells appeared be normal, but subsequent blood vessels revealed...
Three neuronal pentraxins are expressed in brain, the membrane-bound “neuronal pentraxin receptor” (NPR) and secreted proteins NP1 NARP (i.e., NP2). Neuronal bind to AMPARs at excitatory synapses play important, well-documented roles activity-dependent regulation of neural circuits via this binding activity. However, it is unknown whether perform beyond modulating postsynaptic AMPAR-dependent plasticity, they may even act inhibitory synapses. Here, we show that NPR non-neuronal cells...
We studied the role of synaptic ribbon for sound encoding at synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) in mice lacking RIBEYE (RBEKO/KO). Electron immunofluorescence microscopy revealed a lack ribbons an assembly several small active zones (AZs) each contact. Spontaneous sound-evoked firing rates SGNs their compound action potential were reduced, indicating impaired transmission ribbonless IHC-SGN synapses. The temporal precision was recovery SGN-firing from...
Synapse assembly likely requires postsynaptic target recognition by incoming presynaptic afferents. Using newly generated conditional knock-in and knockout mice, we show in this study that latrophilin-2 (Lphn2), a cell-adhesion G protein-coupled receptor presumptive α-latrotoxin receptor, controls the numbers of specific subset synapses CA1-region hippocampal neurons, suggesting Lphn2 acts as synaptic target-recognition molecule. In cultured maintained synapse via instead mechanism, which...
Neurexins are well-characterized presynaptic cell adhesion molecules that engage multifarious postsynaptic ligands and organize diverse synapse properties. However, the precise synaptic localization of neurexins remains enigmatic. Using super-resolution microscopy, we demonstrate neurexin-1 forms discrete nanoclusters at excitatory synapses, revealing a novel organizational feature architecture. Synapses generally contain single nanocluster comprises more than four also includes neurexin-2...
The ribbon is the structural hallmark of cochlear inner hair cell (IHC) afferent synapses, yet its role in information transfer to spiral ganglion neurons (SGNs) remains unclear. We investigated ribbon’s contribution IHC synapse formation and function using KO mice lacking RIBEYE. Despite loss entire structure, synapses retained their spatiotemporal development had a mild hearing deficit. IHCs fewer synaptic vesicles reduced exocytosis response brief depolarization; high stimulus level...
Connexin45 (Cx45) is known to be expressed in the retina, but its functional analysis was problematic because general deletion of Cx45 coding DNA resulted cardiovascular defects and embryonic lethality at day 10.5. We generated mice with neuron-directed concomitant activation enhanced green fluorescent protein (EGFP). EGFP labeling observed bipolar, amacrine, ganglion cell populations. Intracellular microinjection dyes EGFP-labeled somata combined immunohistological markers revealed...
Heterozygous mutations in the syntaxin-binding protein 1 (STXBP1) gene, which encodes Munc18-1, a core component of presynaptic membrane-fusion machinery, cause infantile early epileptic encephalopathy (Ohtahara syndrome), but it is unclear how partial loss Munc18-1 produces this severe clinical presentation. Here, we generated human ES cells designed to conditionally express heterozygous and homozygous STXBP1 loss-of-function studied isogenic WT STXBP1-mutant neurons derived from these...
The molecular mechanisms regulating skeletal muscle regeneration and differentiation are not well understood. We analyzed the expression of connexins (Cxs) 40, 43 45 in normal regenerating tibialis anterior primary cultures differentiating myoblasts adult newborn mice, respectively. Cxs 43, but were strongly expressed their was upregulated during regeneration. Furthermore, functional role Cx43 examined after induced deletion transgenic mice. In vivo, inducible delayed formation myofibers...
Neuroligins (NLs) are postsynaptic cell-adhesion molecules that implicated in humans autism spectrum disorders because the genes encoding NL3 and NL4 mutated rare cases of familial autism. NLs highly conserved evolutionarily, except no was detected currently available mouse genome sequence assemblies. We now demonstrate mice express a distant variant rapidly evolved from other mammalian exhibits variations even between different strains. Despite its divergence, binds neurexins is transported...
Aim: PREDICTIVE™ (Predictable Results and Experience in Diabetes through Intensification Control to Target: An International Variability Evaluation) is a large, multi‐national, observational study assessing the safety efficacy of insulin detemir. We report design, population characteristics baseline observations, including cross‐sectional analysis, from 19 911 patients with type 1 or 2 diabetes. Methods: Patients diabetes requiring basal are prescribed detemir followed up for 12–52 weeks....
The primary rod pathway in mammals contains gap junctions between AII amacrine cells and ON cone bipolar which relay the signal into under scotopic conditions. Two junctional proteins, connexin36 (Cx36) connexin45 (Cx45), appear to play a pivotal role this because lack of either protein leads an impairment visual transmission To investigate whether these connexins form heterotypic cells, we used newly developed Cx45 antibodies studied cellular subcellular distribution mouse retina....
Gap junction coupling synchronizes activity among neurons in adult neural circuits, but its role coordinating during development is less known. The developing retina exhibits retinal waves—spontaneous depolarizations that propagate interneurons and drive ganglion cells (RGCs) to fire correlated bursts of action potentials. During development, two connexin isoforms, connexin36 (Cx36) Cx45, are expressed bipolar RGCs, therefore provide a potential substrate for network activity. To determine...
Abstract Rod photoreceptor synapses use large, ribbon-type active zones for continuous synaptic transmission during light and dark. Since ribbons are physically connected to the zones, we asked whether illumination-dependent changes of influence Cav1.4/RIM2 protein clusters at zone these effects require presence ribbon. We found that ribbon length presynaptic tightly correlated. Dark-adaptation did not change number puncta. However, mean increased significantly dark-adaptation when tonic...
Abstract Tracheal tuft cells shape immune responses in the airways. While some of these effects have been attributed to differential release either acetylcholine, leukotriene C4 and/or interleukin-25 depending on activating stimuli, cell-dependent mechanisms underlying recruitment and activation are incompletely understood. Here we show that Pseudomonas aeruginosa infection activates mouse cells, which ATP via pannexin 1 channels. Taste signaling through Trpm5 channel is essential for...
Probasin protein was originally identified as a basic present in rat prostate epithelium. So far, its physiological role, origin, and presence other species including humans remain largely elusive. With the ever-growing number of genome assemblies, thus probasin genes (Pbsn/PBSN) have only been predicted subset rodent genomes. In this study, we addressed phylogeny found them to be exclusively members superfamily Muroidea. It first emerged so-called pseudoautosomal region, subtelomeric gene...
Direction selectivity, a key feature of visual perception, originates in the retina and is transmitted by bistratified ganglion cells that, rabbit retina, exhibit particular coupling pattern. We intracellularly labeled different transgenic mouse lines, allowing morphological classification cells, an analysis their pattern, molecular identification connexins responsible for coupling. Based on dendritic characteristics including co-fasciculation with dendrites cholinergic starburst amacrine we...