A5063416309- Cellular transport and secretion
- Advanced Fluorescence Microscopy Techniques
- Lipid Membrane Structure and Behavior
- Microtubule and mitosis dynamics
- Advanced Electron Microscopy Techniques and Applications
- Neuroscience and Neuropharmacology Research
- Retinal Development and Disorders
- RNA regulation and disease
- Electrolyte and hormonal disorders
- Cell Image Analysis Techniques
- Viral Infections and Immunology Research
- Photoreceptor and optogenetics research
- Neuroendocrine regulation and behavior
- Single-cell and spatial transcriptomics
- Neurobiology and Insect Physiology Research
- RNA Research and Splicing
- Photosynthetic Processes and Mechanisms
- Cellular Mechanics and Interactions
- Nuclear Structure and Function
- Pancreatic function and diabetes
- Neuroinflammation and Neurodegeneration Mechanisms
- interferon and immune responses
- PI3K/AKT/mTOR signaling in cancer
- Near-Field Optical Microscopy
- Caveolin-1 and cellular processes
Charité - Universitätsmedizin Berlin
2015-2025
Freie Universität Berlin
2011-2024
Humboldt-Universität zu Berlin
2019-2024
Leibniz Association
2014-2018
Leibniz-Forschungsinstitut für Molekulare Pharmakologie
2011-2017
Leibniz Institute for Neurobiology
2015
Forschungsverbund Berlin
2013
Columbia University
2004-2009
Rockefeller University
2000-2003
A critical microtubule (MT) polarization event in cell migration is the Rho/mDia-dependent stabilization of a subset MTs oriented toward direction migration. Although mDia nucleates actin filaments, it unclear whether this or separate activity underlies MT stabilization. We generated two mutants (K853A and I704A) constitutively active version mDia2 containing formin homology domains 1 2 (FH1FH2) found that they still induced stable bound to TIP proteins EB1 APC, which have also been...
The nucleus is the main microtubule-organizing center (MTOC) in muscle cells due to accumulation of centrosomal proteins and microtubule (MT) nucleation activity at nuclear envelope (NE) [1Bugnard E. Zaal K.J.M. Ralston Reorganization during differentiation.Cell Motil. Cytoskeleton. 2005; 60: 1-13Crossref PubMed Scopus (113) Google Scholar, 2Fant X. Srsen V. Espigat-Georger A. Merdes Nuclei non-muscle bind centrosome upon fusion with differentiating myoblasts.PLoS ONE. 2009; 4: e8303Crossref...
Single molecule-based super-resolution methods have become important tools to study nanoscale structures in cell biology. However, the complexity of multi-colour applications has prevented them from being widely used amongst biologists. Direct stochastic optical reconstruction microscopy (dSTORM) offers a simple way perform single molecule imaging without need for an activator fluorophore and compatible with many conventionally fluorophores. The search ideal dye pairs suitable dual-colour...
Abstract Clathrin-mediated endocytosis (CME) involves membrane-associated scaffolds of the bin-amphiphysin-rvs (BAR) domain protein family as well GTPase dynamin, and is accompanied perhaps triggered by changes in local lipid composition. How recruitment, scaffold assembly membrane deformation spatiotemporally controlled coupled to fission poorly understood. We show computational modelling super-resolution imaging that phosphatidylinositol 3,4-bisphosphate [PI(3,4)P 2 ] synthesis within...
Abstract Neuroinflammation including interleukin (IL)-12/IL-23-signaling is central to Alzheimer’s disease (AD) pathology. Inhibition of p40, a subunit IL-12/IL-23, attenuates pathology in AD-like mice; however, its signaling mechanism and expression pattern remained elusive. Here we show that IL-12 receptors are predominantly expressed neurons oligodendrocytes APPPS1 mice patients with AD, whereas IL-23 receptor transcripts barely detectable. Consistently, deletion the neuroectodermal cells...
Total internal reflection fluorescence microscopy has been applied to image the final stage of constitutive exocytosis, which is fusion single post-Golgi carriers with plasma membrane. The use a membrane protein tagged green fluorescent allowed kinetics be followed time resolution 30 frames/s. Quantitative analysis undergoing easily distinguished from moving perpendicularly flattening into seen as simultaneous rise in total, peak, and width intensity. duration this process depends on size...
Cell migration might involve biased membrane traffic toward the leading edge to facilitate building of extracellular matrix, protrusions and adhesion plaques. We tested hypothesis that secretory vesicles are preferentially delivered lamella in wound-edge fibroblasts. Single fusion events containing LDLR-GFP were mapped by total internal reflection fluorescence microscopy (TIR-FM). In migrating fibroblasts, exocytic polarized towards edge. After disrupting microtubules with nocodazole,...
Precise multicolor single molecule localization‐based microscopy (SMLM) requires bright probes with compatible photo‐chemical and spectral properties to resolve distinct molecular species at the nanoscale. The accuracy of SMLM is further challenged by color channel crosstalk chromatic alignment errors. These constrains limit applicability known reversibly switchable organic dyes for optimized SMLM. Here, we tested 28 commercially available their suitability super‐resolve a cellular...
Abstract Assembly and maturation of synapses at the Drosophila neuromuscular junction (NMJ) depend on trans-synaptic neurexin/neuroligin signalling, which is promoted by scaffolding protein Syd-1 binding to neurexin. Here we report that scaffold spinophilin binds C-terminal portion neurexin needed limit signalling acting antagonistic Syd-1. Loss presynaptic results in formation excess, but atypically small active zones. Neuroligin-1/neurexin-1/Syd-1 levels are increased mutant NMJs, removal...
All synapses require fusion-competent vesicles and coordinated Ca2+-secretion coupling for neurotransmission, yet functional anatomical properties are diverse across different synapse types. We show that the presynaptic protein RIM-BP2 has diversified functions in neurotransmitter release at central murine thus contributes to synaptic diversity. At hippocampal pyramidal CA3-CA1 synapses, loss a mild effect on release, by only regulating coupling. However, mossy fiber substantial impact...
Virus infection triggers inflammation and, may impose nutrient shortage to the heart. Supported by type I interferon (IFN) signalling, cardiomyocytes counteract various effector processes, with IFN-stimulated gene of 15 kDa (ISG15) system being intensively regulated and protein modification ISG15 protecting mice Coxsackievirus B3 (CVB3) infection. The underlying molecular aspects how affects functional properties respective substrates in heart are unknown.
In several cell types, specific membrane proteins are retained intracellularly and rapidly redistributed to the surface in response stimulation. fat muscle, GLUT4 glucose transporter is dynamically because it internalized slowly recycled plasma membrane. Insulin increases recycling of GLUT4, resulting a net translocation surface. We have shown that fibroblasts also an insulin-regulated mechanism. Here we show within transferrin receptor-containing general endosomal compartment Chinese...
Sustained fast neurotransmission requires the rapid replenishment of release-ready synaptic vesicles (SVs) at presynaptic active zones. Although machineries for exocytic fusion and subsequent endocytic membrane retrieval have been well characterized, little is known about mechanisms underlying recruitment SVs to release sites. Here we show that Down syndrome-associated scaffold protein intersectin 1 a crucial factor SVs. Genetic deletion expression or acute interference with function...
Abstract Neurotransmission relies on the calcium-triggered exocytic fusion of non-peptide neurotransmitter-containing small synaptic vesicles (SVs) with presynaptic membrane at active zones (AZs) followed by compensatory endocytic retrieval SV membranes. Here, we study diffusional fate newly exocytosed proteins in hippocampal neurons high-resolution time-lapse imaging. Newly rapidly disperse within first seconds post until confined bouton. Rapid spread and confinement is slow reclustering...
Biosynthetic cargo is transported away from the Golgi in vesicles via microtubules. In cell periphery are believed to engage actin and then dock fusion sites at plasma membrane. Using dual-color total internal reflection fluorescence microscopy, we observed that microtubules extended within 100 nm of membrane post-Golgi remained on up membrane, even as initiated. Disruption eliminated tubular shapes altered events: required multiple fusions deliver all their contrast, effects disrupting...
Neurotransmission involves the exo-endocytic cycling of synaptic vesicles (SVs) within nerve terminals. Exocytosis is facilitated by a cytomatrix assembled at active zone (AZ). The precise spatial and functional relationship between exocytic fusion SVs AZ membranes endocytic SV retrieval unknown. Here, we identify scaffold G protein coupled receptor kinase 2 interacting (GIT) as component AZ-associated regulator endocytosis. GIT1 its D. melanogaster ortholog, dGIT, are shown to directly...
G protein-coupled receptors (GPCRs) represent the most important drug targets. Although smallest functional unit of a GPCR is monomer, it became clear in past decades that vast majority form dimers. Only very recently, however, data were presented some may fact be expressed as mixture monomers and dimers interaction receptor protomers dynamic. To date, equilibrium measurements restricted to plasma membrane due experimental limitations. We have addressed question where this established for...
Abstract The precision of single‐molecule localization‐based super‐resolution microscopy, including dSTORM, critically depends on the number detected photons per localization. Recently, reductive caging fluorescent dyes followed by UV‐induced recovery in oxidative buffer systems was used to increase photon yield and thereby localization single‐color dSTORM. By screening 39 for their fluorescence kinetics, we identify novel that are suitable multicolor caged Using a dye pair suited...