A5054535424- Cellular transport and secretion
- Lipid Membrane Structure and Behavior
- Neuroscience and Neuropharmacology Research
- Retinal Development and Disorders
- Photoreceptor and optogenetics research
- Erythrocyte Function and Pathophysiology
- Advanced Fluorescence Microscopy Techniques
- Protist diversity and phylogeny
- Advanced Electron Microscopy Techniques and Applications
- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Neural dynamics and brain function
- Stress Responses and Cortisol
- Cell Adhesion Molecules Research
- S100 Proteins and Annexins
- Neurobiology and Insect Physiology Research
- Ion channel regulation and function
- Marine Invertebrate Physiology and Ecology
- Prenatal Screening and Diagnostics
- Machine Learning in Materials Science
- Neuroscience and Neural Engineering
- Nerve injury and regeneration
- Calcium signaling and nucleotide metabolism
- RNA regulation and disease
University Medical Center
2024
Max Planck Institute for Multidisciplinary Sciences
2022-2024
Max Planck Institute of Experimental Medicine
2011-2021
Max Planck Society
2010-2014
Brain Research New Zealand
2013
University of Otago
2013
German Primate Center
2008-2009
Consejo Nacional de Investigaciones Científicas y Técnicas
2005
Instituto Tecnológico de Chascomús
2005
Mammalian oocytes are filled with poorly understood structures called cytoplasmic lattices. First discovered in the 1960s and speculated to correspond mammalian yolk, ribosomal arrays, or intermediate filaments, their function has remained enigmatic date. Here, we show that lattices sites where store essential proteins for early embryonic development. Using super-resolution light microscopy cryoelectron tomography, composed of filaments a high surface area, which contain PADI6 subcortical...
Dendritic spines are the major transmitter reception compartments of glutamatergic synapses in most principal neurons mammalian brain and play a key role function nerve cell circuits. The formation functional spine is thought to be critically dependent on presynaptic signaling. By analyzing CA1 pyramidal mutant hippocampal slice cultures that essentially devoid release, we demonstrate maintenance dendrites independent synaptic glutamate release.
The Munc13 gene family encodes molecules located at the synaptic active zone that regulate reliability of synapses to encode information over a wide range frequencies in response action potentials. In CNS, proteins are critical regulating neurotransmitter release and plasticity. Although Munc13-1 is essential for transmission, it paradoxical Munc13-2 Munc13-3 functionally dispensable some synapses, although their loss other leads increases frequency-dependent facilitation. We addressed this...
Ribbon synapses of cochlear inner hair cells (IHCs) employ efficient vesicle replenishment to indefatigably encode sound. In neurons, neuroendocrine and immune cells, depends on proteins the mammalian uncoordinated 13 (Munc13) Ca2+-dependent activator for secretion (CAPS) families, which prime vesicles exocytosis. Here, we tested whether Munc13 CAPS also regulate exocytosis in mouse IHCs by combining immunohistochemistry with auditory systems physiology IHC patch-clamp recordings mice...
Synaptic vesicle tethering, priming, and neurotransmitter release require a coordinated action of multiple protein complexes. While physiological experiments, interaction data, structural studies purified systems were essential for our understanding the function individual complexes involved, they cannot resolve how actions integrate. We used cryo-electron tomography to simultaneously image presynaptic lipids at molecular resolution in their native composition, conformation, environment. Our...
Loss-of-function mutations in the synaptic adhesion protein Neuroligin-4 are among most common genetic abnormalities associated with autism spectrum disorders, but little is known about function of and consequences its loss. We assessed network characteristics knockout mice, focusing on hippocampus as a model brain region critical role cognition memory, found that deletion causes subtle defects composition GABAergic synapses hippocampal CA3 region. Interestingly, these changes accompanied by...
Although similar in molecular composition, synapses can exhibit strikingly distinct functional transmitter release and plasticity characteristics. To determine whether ultrastructural differences co-define this heterogeneity, we combine hippocampal organotypic slice cultures, high-pressure freezing, freeze substitution, 3D-electron tomography to compare two functionally synapses: Schaffer collateral mossy fiber synapses. We find that synapses, which a lower probability stronger short-term...
Electron microscopy can resolve synapse ultrastructure with nanometer precision, but the capture of time-resolved, activity-dependent synaptic membrane-trafficking events has remained challenging, particularly in functionally distinct synapses a tissue context. We present method that combines optogenetic stimulation-coupled cryofixation ("flash-and-freeze") and electron to visualize membrane trafficking synapse-state-specific changes presynaptic vesicle organization high spatiotemporal...
The brain extracellular matrix (ECM) consists of extremely long-lived proteins that assemble around neurons and synapses, to stabilize them. ECM is thought change only rarely, in relation neuronal plasticity, through proteolysis renewed protein synthesis. We report here an alternative remodeling mechanism, based on the recycling molecules. Using multiple labeling imaging assays, from super-resolution optical nanoscale secondary ion mass spectrometry, both culture slices, we find a key...
Neuronal remodeling is a fundamental process by which the brain responds to environmental influences, e.g., during stress. In hippocampus, chronic stress causes retraction of dendrites in CA3 pyramidal neurons. We have recently identified glycoprotein M6a as stress-responsive gene hippocampal formation. This down-regulated hippocampus both socially and physically stressed animals, this effect can be reversed antidepressant treatment. present work, we analyzed biological function protein....
SNARE protein-driven secretion of neurotransmitters from synaptic vesicles is at the center neuronal communication. In absence cytosolic protein Munc18-1, comes to a halt. Although it believed that Munc18-1 orchestrates complexes, its mode action still matter debate. particular, has been challenging clarify role tight Munc18/syntaxin 1 complex, because this interaction interferes strongly with syntaxin's ability form complex. two regions syntaxin, N-peptide and remainder in closed...
Munc13 proteins are essential regulators of exocytosis. In hippocampal glutamatergic neurons, the genetic deletion Munc13s results in complete loss primed synaptic vesicles (SVs) direct contact with presynaptic active zone membrane, and a total block neurotransmitter release. Similarly drastic consequences detectable striatal GABAergic neurons. We show here that, adult mouse retina, two Munc13-2 splice variants bMunc13-2 ubMunc13-2 selectively localized to conventional ribbon synapses,...
It is currently unknown whether the molecular steps of large dense-core vesicle (LDCV) docking and priming are identical to corresponding reactions in synaptic (SV) exocytosis. Munc13s essential for SV priming, we systematically analyzed their role LDCV exocytosis using chromaffin cells lacking individual isoforms. We show that particularly Munc13-2 plays a fundamental exocytosis, but contrast synapses Munc13s, do not exhibit defect. further demonstrate ubMunc13-2 Munc13-1 confer...
Presynaptic active zones (AZs) are unique subcellular structures at neuronal synapses, which contain a network of specific proteins that control synaptic vesicle (SV) tethering, priming, and fusion. Munc13s core AZ with an essential function in SV priming. In hippocampal neurons, two different Munc13s-Munc13-1 bMunc13-2-mediate opposite forms presynaptic short-term plasticity thus differentially affect characteristics. We found most presynapses cortical neurons only Munc13-1, whereas ∼10%...
Synaptotagmins confer calcium-dependence to the exocytosis of secretory vesicles, but how coexpressed synaptotagmins interact remains unclear. We find that synaptotagmin-1 and synaptotagmin-7 when present alone act as standalone fast slow Ca 2+ -sensors for vesicle fusion in mouse chromaffin cells. When together, are found largely non-overlapping clusters on dense-core vesicles. Synaptotagmin-7 stimulates -dependent priming inhibits depriming, it promotes ubMunc13-2- phorbolester-dependent...
Munc13-3 is a presynaptic protein implicated in vesicle priming that strongly expressed cerebellar granule cells (GCs). Mice deficient of ( −/− ) show an increased paired-pulse ratio (PPR), which led to the hypothesis increases release probability p r vesicles. In present study, we analyzed unitary synaptic connections between GCs and basket acute slices from wild-type mice. Unitary EPSCs recorded showed normal kinetics latency but significantly PPR fraction failures. A quantal analysis...
SUMO1-conjugation of proteins at neuronal synapses is considered to be a major post-translational regulatory process in nerve cell and synapse function, but the published evidence for contradictory. We employed multiple genetic mouse models stringently controlled biochemical immunostaining analyses synaptic SUMO1-conjugation. By using knock-in reporter line expressing tagged SUMO1, we could not detect seven previously proposed SUMO1-targets brain. Further, cultured neurons from wild-type...