A5021185824- Genomics and Chromatin Dynamics
- Advanced Fluorescence Microscopy Techniques
- Neuroscience and Neuropharmacology Research
- Cellular Mechanics and Interactions
- Blood properties and coagulation
- DNA Repair Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Platelet Disorders and Treatments
- Microtubule and mitosis dynamics
- RNA Research and Splicing
- Cellular transport and secretion
- Advanced Electron Microscopy Techniques and Applications
- Skin and Cellular Biology Research
- Chromosomal and Genetic Variations
- Axon Guidance and Neuronal Signaling
- Neuroinflammation and Neurodegeneration Mechanisms
- Streptococcal Infections and Treatments
- Cell Adhesion Molecules Research
- Ubiquitin and proteasome pathways
- Cell Image Analysis Techniques
- Optical Coherence Tomography Applications
- Heat shock proteins research
- Nuclear Structure and Function
- Connexins and lens biology
- Molecular Biology Techniques and Applications
Erasmus University Rotterdam
2016-2025
Erasmus MC
2016-2025
Imaging Center
2019-2025
Optica
2019-2023
Erasmus Optical Imaging Centre
2015-2020
University Medical Center Utrecht
2010-2020
Rotterdam University of Applied Sciences
2019
Meertens Institute
2013-2016
Utrecht University
2012
Heidelberg University
2010
Myelination, the insulating ensheathment of axons by oligodendrocytes, is thought to both optimize signal propagation and provide metabolic support. Despite well-established physiological importance myelination neuronal function, relatively little known about GABAergic interneurons in cerebral cortex. Here, we report that a large fraction myelin mouse cortex ensheaths interneurons, reaching up 80% hippocampal subregions. Moreover, find very high proportion neocortical parvalbumin (PV)...
Following exit from mitosis, RNA Pol II is required for reestablishing 3D genome folding by loading cohesin complexes onto DNA.
Abstract Focal adhesions (FAs) are multiprotein structures that link the intracellular cytoskeleton to extracellular matrix. They mediate cell adhesion and migration, crucial many (patho-) physiological processes. We examined in two types from different species binding dynamics of functionally related FA protein pairs: paxillin vinculin versus zyxin VASP. In photobleaching experiments ~40% remained stably associated with a for over half an hour. Zyxin VASP predominantly displayed more...
Cohesin is a ring-shaped multiprotein complex that crucial for 3D genome organization and transcriptional regulation during differentiation development. It also confers sister chromatid cohesion facilitates DNA damage repair. Besides its core subunits SMC3, SMC1A, RAD21, cohesin in somatic cells contains one of two orthologous STAG subunits, STAG1 or STAG2. How these variable affect the function still unclear. STAG1- STAG2-cohesin were initially proposed to organize at telomeres centromeres,...
Chromatin is dynamically reorganized when DNA replication forks are challenged. However, the process of epigenetic reorganization and its implication for fork stability poorly understood. Here we discover a checkpoint-regulated cascade chromatin signalling that activates histone methyltransferase EHMT2/G9a to catalyse heterochromatin assembly at stressed forks. Using biochemical single molecule fibre approaches, show G9a together with SUV39h1 induces compaction by accumulating repressive...
Abstract Mechanical forces are integrated at cadherin-based adhesion complexes to regulate morphology and strength of cell-cell junctions organization associated F-actin. A central mechanosensor the cadherin complex is α-catenin, whose stretching recruits vinculin strength. The identity F-actin regulating signals that also activated by mechanical has remained elusive. Here we identify actin-regulators VASP, zyxin TES as members punctate, tensile called Focal Adherens Junctions (FAJ) show...
Abstract Podosomes are cytoskeletal structures crucial for cell protrusion and matrix remodelling in osteoclasts, activated endothelial cells, macrophages dendritic cells. In these hundreds of podosomes spatially organized diversely shaped clusters. Although we others established individual as micron-sized mechanosensing protrusive units, the exact scope spatiotemporal organization podosome clustering remain elusive. By integrating a newly developed extension Spatiotemporal Image Correlation...
Basement membrane transmigration during embryonal development, tissue homeostasis and tumor invasion relies on invadosomes, a collective term for invadopodia podosomes. An adequate structural framework this process is still missing. Here, we reveal the modular actin nano-architecture that enables podosome protrusion mechanosensing. The protrusive core contains central branched module encased by linear module, each harboring specific interactors isoforms. From core, two modules radiate:...
GABAergic fast-spiking parvalbumin-positive (PV) interneurons are frequently myelinated in the cerebral cortex. However, factors governing topography of cortical interneuron myelination remain incompletely understood. Here, we report that segmental along neocortical axons is strongly predicted by joint combination interbranch distance and local axon caliber. Enlargement PV+ increased axonal myelination, while reduced cell size led to decreased myelination. Next, considered regular-spiking...
The group 1 metabotropic glutamate receptors and 5 (mGluR1/5) have been implicated in mechanisms of synaptic plasticity may serve as potential therapeutic targets autism spectrum disorders. interactome mGluRs has remained largely unresolved. Using a knockout-controlled interaction proteomics strategy we examined the mGluR5 protein complex two brain regions, hippocampus cortex, identified mGluR1 its major interactor addition to well described Homer proteins. We confirmed presence mGluR1/5 by...
Podosomes are actin-rich adhesion structures that depend on Arp2/3 complex-based actin nucleation. We now report the identification of formins FHOD1 and INF2 as novel components additional actin-based regulators podosomes in primary human macrophages. surrounds podosome core is also present at podosome-connecting cables, whereas localizes cap structure. Using a variety microscopy-based methods, including semiautomated reformation assay, measurement oscillations, FRAP analysis single...
Abstract Protein correlation profiling might assist in defining co-assembled proteins and subcellular distribution. Here, we quantified the proteomes of five biochemically isolated mouse brain cellular sub-fractions, with emphasis on synaptic compartments, from three regions, hippocampus, cortex cerebellum. We demonstrated expected co-fractionation canonical belonging to same functional groups. The enrichment profiles also suggested presence many novel pre- post-synaptic proteins. Using...
The Gleason score is one of the most important parameters for therapeutic decision-making in prostate cancer patients. growth patterns are defined by their histological features on 4- to 5-µm cross sections, and little known about three-dimensional architecture. Our objective was characterize architecture patterns. Intact tissue punches (n = 46) representative from radical prostatectomy specimens were fluorescently stained with antibodies targeting Keratin 8/18 5 detection luminal basal...
The recombinase RAD51, and its meiosis-specific paralog DMC1 localize at DNA double-strand break (DSB) sites in meiotic prophase. While both proteins are required during prophase, their spatial organization DSB repair is not fully understood. Using super-resolution microscopy on mouse spermatocyte nuclei, we aimed to define relative position foci, how these vary time. We show that a large fraction of foci (38%) consisted single RAD51 nanofocus (D1R1 configuration) were partially overlapping...
Biallelic loss-of-function variants in SMPD4 cause a rare and severe neurodevelopmental disorder with progressive congenital microcephaly early death. encodes sphingomyelinase that hydrolyses sphingomyelin into ceramide at neutral pH can thereby affect membrane lipid homeostasis. localizes to the membranes of endoplasmic reticulum nuclear envelope interacts pore complexes (NPC). We refine clinical phenotype by describing five individuals from three unrelated families longitudinal data due...
The single most common microbe causing cardiovascular infections is Staphylococcus aureus (S. aureus). S. produces coagulase that converts fibrinogen to fibrin, which incorporated into biofilms. This process aids in adherence intravascular structures, defense against the host immune system, and resistance antimicrobial treatment. Despite its significance, fibrin formation biofilms remains poorly understood. Therefore, this study aimed elucidate early development of Clinically isolated...
Recessive mutations in RTTN, encoding the protein rotatin, were originally identified as cause of polymicrogyria, a cortical malformation. With time, wide variety other brain malformations has been ascribed to RTTN mutations, including primary microcephaly. Rotatin is centrosomal possibly involved centriolar elongation and ciliogenesis. However, function rotatin development largely unknown molecular disease mechanism underlying not yet elucidated. We performed both clinical cell biological...
Faithful mitotic chromosome segregation is required for the maintenance of genomic stability. We discovered phosphorylation histone H2B at serine 6 (H2B S6ph) as a new chromatin modification site and found that this occurs during early phases inner centromeres pericentromeric heterochromatin. This directly mediated by cyclin B1–associated CDK1, indirectly Aurora B, antagonized PP1-mediated dephosphorylation. S6ph impairs binding chaperone SET (I2PP2A), which important fidelity. Injection...
Various aspects of image filtering affect the final quality in Structured Illumination Microscopy, particular regularization parameter and type function, relative height side bands, shape apodization function. We propose an filter without adjustable parameters based on application Lukosz bound order to guarantee a non-negative point spread Simulations digital resolution charts experimental data chromatin structures actin filaments show artefact free reconstructions for wide range parameters....
The majority of excitatory postsynaptic currents in the brain are gated through AMPA-type glutamate receptors, kinetics and trafficking which can be modulated by auxiliary proteins. It remains to elucidated whether how proteins modulate synaptic function contribute procedural memory formation. In this study, we report that receptor (AMPAR) protein SHISA6 (CKAMP52) is expressed cerebellar Purkinje cells, where it co-localizes with GluA2-containing AMPARs. absence cells results severe...
The ubiquitin system plays an important role in trafficking of signaling receptors from the plasma membrane to lysosomes. Triad1 is a ligase that catalyzes formation poly-ubiquitin chains linked via lysine-48 as well lysine-63 residues. We show depletion affects sorting both growth hormone and epidermal factor. Triad1-depleted cells accumulate ligands endosomes. While fluid phase transport lysosomes reduced absence Triad1, receptor can recycle back together with transferrin. Using immune...