A5015381590- Cellular transport and secretion
- Retinal Development and Disorders
- Neuroscience and Neuropharmacology Research
- Photoreceptor and optogenetics research
- RNA and protein synthesis mechanisms
- Lipid Membrane Structure and Behavior
- Biotin and Related Studies
- RNA regulation and disease
- RNA Research and Splicing
- Neuroinflammation and Neurodegeneration Mechanisms
- Advanced Proteomics Techniques and Applications
- Genetics and Neurodevelopmental Disorders
- Microtubule and mitosis dynamics
- Ubiquitin and proteasome pathways
- Click Chemistry and Applications
- RNA modifications and cancer
- Synthesis and Reactions of Organic Compounds
- Autophagy in Disease and Therapy
- Antimicrobial Peptides and Activities
- Endoplasmic Reticulum Stress and Disease
- Chromatin Remodeling and Cancer
- Light effects on plants
- Erythrocyte Function and Pathophysiology
- Photosynthetic Processes and Mechanisms
- CRISPR and Genetic Engineering
Max Planck Institute for Brain Research
2014-2024
Max Planck Society
2004-2021
University of California San Diego Medical Center
2020
Synaptic Research (United States)
2013
Goethe University Frankfurt
2012
Friedrich-Alexander-Universität Erlangen-Nürnberg
2006-2010
Leibniz Institute for Neurobiology
1999-2007
University of Veterinary Medicine Hannover, Foundation
1991-1992
The ribbon complex of retinal photoreceptor synapses represents a specialization the cytomatrix at active zone (CAZ) present conventional synapses. In mice deficient for CAZ protein Bassoon, ribbons are not anchored to presynaptic membrane but float freely in cytoplasm. Exploiting this phenotype, we dissected molecular structure complex. Identifiable proteins segregate into two compartments ribbon: ribbon-associated compartment including Piccolo, RIBEYE, CtBP1/BARS, RIM1, and motor KIF3A, an...
Significance Proteins are the key drivers of neuronal synaptic function. The regulation gene expression is important for formation and modification synapses throughout lifespan. complexity dendrites axons imposes unique challenges protein supply at remote locations. discovery messenger RNAs (mRNAs) ribosomes near has shown that local synthesis represents an solution to this challenge. Here we used RNA sequencing ribosome determine directly population mRNAs present in process translation cell...
Neurons build synaptic contacts using different protein combinations that define the specificity, function, and plasticity potential of synapses; however, diversity proteomes remains largely unexplored. We prepared synaptosomes from 7 transgenic mouse lines with fluorescently labeled presynaptic terminals. Combining microdissection 5 brain regions fluorescent-activated synaptosome sorting (FASS), we isolated analyzed 18 synapse types. discovered ∼1,800 unique synapse-type-enriched proteins...
Although mRNAs are localized in the processes of excitatory neurons, it is still unclear whether interneurons also localize a large population mRNAs. In addition, variability mRNA within and between cell types unknown. Here we describe unbiased transcriptomic characterization subcellular compartments hundreds single neurons. We separately profiled dendritic somatic transcriptomes individual rat hippocampal neurons investigated abundances soma dendrites glutamatergic GABAergic found that,...
Localized translation is vital to polarized cells and requires precise robust distribution of different mRNAs ribosomes across the cell. However, underlying molecular mechanisms are poorly understood important players lacking. Here, we discovered a Rab5 effector, five-subunit endosomal RNA/ribosome intermediary (FERRY) complex, that recruits early endosomes through direct mRNA-interaction. FERRY displays preferential binding certain groups transcripts, including encoding mitochondrial...
Abstract The retinal photoreceptor ribbon synapse is a chemical structurally and functionally specialized for the tonic release of neurotransmitter. It characterized by presynaptic ribbon, an electron‐dense organelle at active zone covered hundreds synaptic vesicles. In conventional synapses, dense‐core transport vesicles carrying set proteins are implicated in early steps formation. spheres suggested to be involved assembly, but nothing known about molecular composition these organelles....
purpose. Photoreceptor ribbon synapses translate light-dependent changes of membrane potential into graded transmitter release via L-type voltage-dependent calcium channel (VDCC) activity. Functional abnormalities (e.g., a reduced electroretinogram b-wave), arising from mutations presynaptic proteins, such as Bassoon and the VDCCα1 subunit Cacna1f, have been shown to altered release. subtype expression in wild-type mutant mice was examined, investigate underlying pathologic mechanism....
How size and shape of presynaptic active zones are regulated at the molecular level has remained elusive. Here we provide insight from studying rod photoreceptor ribbon-type after disruption CAST/ERC2, one cytomatrix zone (CAZ) proteins. Rod photoreceptors were present in normal numbers, a-wave electroretinogram (ERG)--reflecting their physiological population response--was unchanged CAST knock-out (CAST(-/-)) mice. Using immunofluorescence electron microscopy, found that zones, Ca(2+)...
Fluorescent labeling of proteins by genetically encoded fluorescent protein tags has enabled an enhanced understanding cell biological processes but is restricted to the analysis a limited number identified proteins. This approach does not permit, e.g., unbiased visualization full proteome in situ. We describe here fluorescence-based method follow proteome-wide patterns newly synthesized cultured cells, tissue slices, and whole organism. technique compatible with immunohistochemistry situ...
Abstract Background MeCP2—a chromatin-binding protein associated with Rett syndrome—has two main isoforms, MeCP2-E1 and MeCP2-E2, differing in a few N-terminal amino acid residues. Previous studies have shown brain region-specific expression of these isoforms which, addition to their different cellular localization differential during development, suggest that they may also non-overlapping molecular mechanisms. However, functions E2 remain largely unexplored. Results Here, we show the...
Localized signaling in neuronal dendrites requires tight spatial control of membrane composition. Upon initial synthesis, nascent secretory cargo exits the endoplasmic reticulum (ER) from local zones ER complexity that are spatially coupled to post-ER compartments. Although newly synthesized proteins can be processed locally, mechanisms range transport dendritic segments unknown. Here, we monitored dynamics compartments under regimes low or increased activity. In response activity blockade,...
In the nervous system, myelination of axons enables rapid impulse conduction and is a specialized function glial cells. Myelinating glia are last cell type to emerge in evolution vertebrate systems, presumably ancient jawed vertebrates (gnathostomata) because jawless (agnathans) lack myelin. We have hypothesized that, these unmyelinated species, evolutionary progenitors myelinating cells must existed that should still be present contemporary agnathan species. Here, we used advanced electron...
We examined the feedback between major protein degradation pathway, ubiquitin-proteasome system (UPS), and synthesis in rat mouse neurons. When was inhibited, we observed a coordinate dramatic reduction nascent neuronal cell bodies dendrites. The mechanism for translation inhibition involved phosphorylation of eIF2α, surprisingly mediated by eIF2α kinase 1, or heme-regulated inhibitor (HRI). Under basal conditions, expression HRI is barely detectable. Following proteasome inhibition, levels...
Abstract Neurons are highly compartmentalized cells with tightly controlled subcellular protein organization. While brain transcriptome, connectome and global proteome maps being generated, system-wide analysis of temporal dynamics at the level currently lacking. Here, we perform a temporally-resolved surfaceome primary neuron cultures reveal dynamic surface clusters that reflect functional requirements during distinct stages neuronal development. Direct comparison total pools development...