A5088645695- Lipid Membrane Structure and Behavior
- Cellular transport and secretion
- Hearing, Cochlea, Tinnitus, Genetics
- Connexins and lens biology
- Calcium signaling and nucleotide metabolism
- Biochemical Analysis and Sensing Techniques
- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Photoreceptor and optogenetics research
- Toxoplasma gondii Research Studies
- RNA regulation and disease
- Parasitic Infections and Diagnostics
- Cytomegalovirus and herpesvirus research
- Polyoxometalates: Synthesis and Applications
- Neuroscience and Neural Engineering
- Plant Molecular Biology Research
- Magnetism in coordination complexes
- Fluorine in Organic Chemistry
- Autophagy in Disease and Therapy
- Mitochondrial Function and Pathology
Charité - Universitätsmedizin Berlin
2020-2024
Freie Universität Berlin
1987-2024
Max Delbrück Center
2024
Humboldt-Universität zu Berlin
2022
European Neuroscience Institute Göttingen
2019-2020
Max Planck Society
2019-2020
Universitätsmedizin Göttingen
2013-2020
University of Göttingen
2013-2020
During neurotransmission, presynaptic action potentials trigger synaptic vesicle fusion with the plasma membrane within milliseconds. To visualize dynamics before, during, and right after at central synapses under near-native conditions, we developed an experimental strategy for time-resolved in situ cryo-electron tomography millisecond temporal resolution. We coupled optogenetic stimulation cryofixation confirmed stimulation-induced release of neurotransmitters via cryo-confocal microscopy...
Abstract Endophilins-A are conserved endocytic adaptors with membrane curvature-sensing and -inducing properties. We show here that, independently of their role in endocytosis, endophilin-A1 endophilin-A2 regulate exocytosis neurosecretory vesicles. The number distribution vesicles were not changed chromaffin cells lacking endophilin-A, yet fast capacitance amperometry measurements revealed reduced exocytosis, smaller vesicle pools altered fusion kinetics. levels distributions the main...
Synaptic vesicles (SVs) store and transport neurotransmitters to the presynaptic active zone for release by exocytosis. After release, SV proteins excess membrane are recycled via endocytosis, new SVs can be formed in a clathrin-dependent manner. This process maintains complex molecular composition of through multiple recycling rounds. Previous studies explored proteomic analysis fluorescent microscopy, proposing model an average ( 1 ). However, structural heterogeneity architecture...
Cholesterol is crucial for neuronal synaptic transmission, assisting in the molecular and structural organization of lipid rafts, ion channels, exocytic proteins. Although cholesterol absence was shown to result impaired neurotransmission, how locally traffics its route action are still under debate. Here, we characterized transfer protein ORP2 murine hippocampal neurons. We show that preferentially localizes presynapse. Loss reduces presynaptic levels by 50%, coinciding with a profoundly...
Abstract Synaptic vesicles (SVs) store and transport neurotransmitters to the presynaptic active zone for release by exocytosis. After release, SV proteins excess membrane are recycled via endocytosis, new SVs formed in a clathrin-dependent manner. This process maintains morphology complex molecular composition of through multiple recycling rounds. Previous studies explored proteomic analysis fluorescent microscopy, proposing model an average 1,2 . However, structural heterogeneity...
High-throughput neurotransmission at ribbon synapses of cochlear inner hair cells (IHCs) requires tight coupling neurotransmitter release and balanced recycling synaptic vesicles (SVs) as well rapid restoration sites. Here, we examined the role adaptor protein AP180 (also known SNAP91) for IHC transmission by comparing AP180-knockout (KO) wild-type mice using high-pressure freezing electron tomography, confocal microscopy, patch-clamp membrane capacitance measurements systems physiology. was...
Abstract Inner hair cells (IHCs) are the primary receptors for hearing. They housed in cochlea and convey sound information to brain via synapses with auditory nerve. IHCs have been thought be electrically metabolically independent from each other. We report that, upon developmental maturation, mice 30% of electrochemically coupled ‘mini-syncytia’. This coupling permits transfer fluorescently-labeled metabolites macromolecular tracers. The membrane capacitance, Ca 2+ -current, resting...
The release of neurotransmitters at central synapses is dependent on a cascade protein interactions, specific to the presynaptic compartment. Amongst those dedicated molecules cytosolic complexins play an incompletely defined role as synaptic transmission regulators. Complexins are multidomain SNARE complex binding proteins which confer both inhibitory and stimulatory functions. Using systematic mutagenesis combining reconstituted in vitro membrane fusion assays with electrophysiology...
Abstract The structural stability of synapses directly contrasts with their functional plasticity. This conceptual dichotomy is explained by the assumption that all synaptic plasticity generated via either electrical and/or biochemical signaling. Here, we challenge this dogma revealing an activity-dependent presynaptic response physical in nature. We show dynamic filopodia emerge during action potential discharge and transiently deform boutons to enhance connectivity. Filopodia generation...
SUMMARY Endophilins-A are conserved endocytic adaptors with membrane curvature-sensing and - inducing properties. We show here that, independently of their role in endocytosis, endophilin-A1 endophilin-A2 regulate exocytosis neurosecretory vesicles. The number vesicles was not altered chromaffin cells without endophilin, yet fast capacitance amperometry measurements revealed reduced exocytosis, smaller vesicle pools changed fusion kinetics. Both (brain-enriched) A2 (ubiquitous) rescued...
Abstract Inner hair cells (IHCs) are the primary receptors for hearing. They housed in cochlea and convey sound information to brain via synapses with auditory nerve. IHCs have been thought be electrically metabolically independent from each other. We report that, upon developmental maturation, 30% of electrochemically coupled ‘mini-syncytia’. This coupling permits transfer fluorescently-labeled metabolites macromolecular tracers. The membrane capacitance, Ca 2+ -current, resting current...
ABSTRACT First Person is a series of interviews with the first authors selection papers published in Journal Cell Science, helping early-career researchers promote themselves alongside their papers. Jana Kroll and Özge Demet Özçete are co-first on ‘AP180 promotes release site clearance clathrin-dependent vesicle reformation mouse cochlear inner hair cells’, JCS. Postdoc lab Prof. Dr Christian Rosenmund at Institute Neurophysiology, Charité Universitätsmedizin, Berlin, investigating...
Abstract Starting with the tricarbonyl complex (I) trifluoromethyl isocyanide (III) is synthesized via derivative (II).