A5026872836- Cellular transport and secretion
- Lipid Membrane Structure and Behavior
- Neuroscience and Neuropharmacology Research
- Retinal Development and Disorders
- Genetics and Neurodevelopmental Disorders
- Erythrocyte Function and Pathophysiology
- Photoreceptor and optogenetics research
- Receptor Mechanisms and Signaling
- Pancreatic function and diabetes
- Ion channel regulation and function
- Signaling Pathways in Disease
- Neurogenesis and neuroplasticity mechanisms
- Calcium signaling and nucleotide metabolism
- Neuropeptides and Animal Physiology
- Genetic Associations and Epidemiology
- Neurobiology and Insect Physiology Research
- RNA regulation and disease
- Memory and Neural Mechanisms
- Endoplasmic Reticulum Stress and Disease
- Genomics and Rare Diseases
- Neurotransmitter Receptor Influence on Behavior
- Neuroendocrine regulation and behavior
- Microtubule and mitosis dynamics
- Neuroinflammation and Neurodegeneration Mechanisms
- Single-cell and spatial transcriptomics
Vrije Universiteit Amsterdam
2015-2025
Cognitive Research (United States)
2013-2025
Amsterdam Neuroscience
2016-2025
Amsterdam University Medical Centers
2019-2025
Amsterdam UMC Location Vrije Universiteit Amsterdam
2013-2025
Stanford University
2024
Genomics (United Kingdom)
2006-2023
University Medical Center
2013-2023
Cancer Genomics Centre
2022-2023
University of Amsterdam
1988-2021
Brain function requires precisely orchestrated connectivity between neurons. Establishment of these connections is believed to require signals secreted from outgrowing axons, followed by synapse formation selected Deletion a single protein, Munc18-1, in mice leads complete loss neurotransmitter secretion synaptic vesicles throughout development. However, this does not prevent normal brain assembly, including layered structures, fiber pathways, and morphologically defined synapses. After...
Exocytosis requires formation of SNARE [soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor] complexes between vesicle and target membranes. Recent assessments in reduced model systems have produced divergent estimates the number needed for fusion. Here, we used a titration approach to answer this question intact, cultured chromaffin cells. Simultaneous expression wild-type SNAP-25 mutant unable support exocytosis progressively altered fusion kinetics fusion-pore...
Exosomes are small endosome-derived extracellular vesicles implicated in cell–cell communication and secreted by living cells when multivesicular bodies (MVBs) fuse with the plasma membrane (PM). Current techniques to study exosome physiology based on isolation procedures after secretion, precluding direct dynamic insight into mechanics of biogenesis regulation their release. In this study, we propose real-time visualization MVB–PM fusion overcome these limitations. We designed...
“Spontaneous” Release Trigger Synaptic vesicle release occurs in different phases that can be tightly coupled to action potentials (synchronous), immediately following (asynchronous), or as stochastic events not triggered by (spontaneous). The protein synaptotagmin is thought act the Ca 2+ sensor synchronous phase, but for other two phases, sensors have been identified. Groffen et al. (p. 1614 , published online 11 February) now show cytoplasmic proteins known Doc2 (double C2 domain) are...
During synaptic vesicle fusion, the soluble N -ethylmaleimide-sensitive factor–attachment protein receptor (SNARE) syntaxin-1 exhibits two conformations that both bind to Munc18-1: a “closed” conformation outside SNARE complex and an “open” in complex. Although complexes containing open Munc18-1 are essential for exocytosis, function of closed is unknown. We generated knockin/knockout mice expressed only syntaxin-1B. Syntaxin-1B Open were viable but succumbed generalized seizures at 2 3...
Tetanus toxin (100 nM) when preincubated with guinea pig cerebrocortical synaptosomes for 45 min reduces the final extent of KCl-evoked, Ca(2+)-dependent, glutamate transmitter release to 30% non-intoxicated controls. Similarly, 100 nM Botulinum neurotoxins, types A and B, 90 inhibit 45-60% The toxins preferentially attenuate a slow phase KCl-evoked which may be associated synaptic vesicle mobilization. additionally inhibits aspartate, gamma-aminobutyric acid met-enkephalin from same...
The shape, structure and connectivity of nerve cells are important aspects neuronal function. Genetic epigenetic factors that alter morphology or synaptic localization pre- post-synaptic proteins contribute significantly to output may underlie clinical states. To assess the impact individual genes disease-causing mutations on morphology, reliable methods needed. Unfortunately, manual analysis immuno-fluorescence images neurons quantify shape synapse number, size distribution is...
Prompt recovery after intense activity is an essential feature of most mammalian synapses. Here we show that synapses with reduced expression the presynaptic gene munc18-1 suffer from increased depression during stimulation at glutamatergic, GABAergic, and neuromuscular Conversely, overexpression makes these recover faster. Concomitant changes in readily releasable vesicle pool its refill kinetics were found. The number vesicles docked active zone total per terminal correlated both levels...
Schizophrenia is a highly heritable disorder with polygenic pattern of inheritance and population prevalence ∼1%. Previous studies have implicated synaptic dysfunction in schizophrenia. We tested the accumulated association genetic variants expert-curated gene groups schizophrenia 4673 cases 4965 healthy controls, using functional group analysis. Identifying genes similar cellular function rather than isolation may clinical implications for finding additional drug targets. found that 1026...
Background The variance explained by genetic variants as identified in (genome-wide) association studies is typically small compared to family-based heritability estimates. Explanations of this ‘missing heritability’ have been mainly genetic, such heterogeneity and complex (epi-)genetic mechanisms. Methodology We used comprehensive simulation show that three phenotypic measurement issues also provide viable explanations the missing heritability: complexity, bias, resolution. identify...