A5003522677- Ship Hydrodynamics and Maneuverability
- Structural Integrity and Reliability Analysis
- Blood Pressure and Hypertension Studies
- Ubiquitin and proteasome pathways
- Fluid Dynamics Simulations and Interactions
- Neuroscience and Neuropharmacology Research
- Cellular transport and secretion
- Heart Rate Variability and Autonomic Control
- Adipokines, Inflammation, and Metabolic Diseases
- Hormonal Regulation and Hypertension
- Genetics and Neurodevelopmental Disorders
- Landslides and related hazards
- Ocean Waves and Remote Sensing
- Sodium Intake and Health
- Protein Degradation and Inhibitors
- Regulation of Appetite and Obesity
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Underwater Acoustics Research
- Nutritional Studies and Diet
- Retinal Development and Disorders
- Adipose Tissue and Metabolism
- Lipid Membrane Structure and Behavior
- Engineering Applied Research
- Stress Responses and Cortisol
- Birth, Development, and Health
Max Planck Institute of Experimental Medicine
2014-2024
Kobe University
2018-2023
Foundation for Biomedical Research and Innovation
2018-2023
Gunma University
2020-2023
Niigata University
2006-2023
Max Planck Institute for Multidisciplinary Sciences
2022
Foundation for Biomedical Research
2022
Keio University
2010-2020
ClassNK
2020
Keio University Hospital
2000-2018
PTEN is a tumor suppressor frequently mutated in cancer. Recent reports implicated Nedd4-1 as the E3 ubiquitin ligase for that regulates its stability and nuclear localization. We tested physiological role of regulator by using cells tissues derived from two independently generated strains mice with their gene disrupted. ubiquitination were indistinguishable between wild-type Nedd4-1-deficient cells, an interaction proteins could not be detected. Moreover, subcellular distribution, showing...
Selective synapse development determines how complex neuronal networks in the brain are formed. Complexes of postsynaptic neuroligins and LRRTMs with presynaptic neurexins contribute widely to excitatory development, mutations these gene families increase risk developing psychiatric disorders. We find that LRRTM4 has distinct binding partners, heparan sulfate proteoglycans (HSPGs). HSPGs required mediate synaptogenic activity LRRTM4. shows highly selective expression brain. Within...
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.
Abstract Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease characterized by patchy scarring of the distal with limited therapeutic options and poor prognosis. Here, we show that conditional deletion ubiquitin ligase Nedd4-2 ( Nedd4l ) in epithelial cells adult mice produces sharing key features IPF including bronchiolization increased expression Muc5b peripheral airways, honeycombing characteristic alterations proteome. NEDD4-2 implicated regulation Na +...
Nicotinamide N-methyltransferase (NNMT) catalyses the reaction between nicotinamide (NAM) and S-adenosylmethionine to produce 1-methylnicotinamide S-adenosylhomocysteine. Recently, this enzyme has also been reported modulate hepatic nutrient metabolism, but its role in liver not fully elucidated. We developed transgenic mice overexpressing NNMT elucidate metabolism. When fed a high fat diet containing NAM, precursor for adenine dinucleotide (NAD)
In our previous research, we developed space robot teleoperation technology to achieve control from the ground of effective manual manipulations in orbit. To solve communication time delay teleoperation, propose a mixed force and motion command-based system that is model-based teleoperation. Moreover, have also compact 6-degree-of-freedom haptic interface as master device. The important features are its robustness against modeling errors ability realize exerted by operator at remote site. We...
Cystic fibrosis is caused by impaired ion transport due to mutated cystic transmembrane conductance regulator, accompanied elevated activity of the amiloride-sensitive epithelial Na(+) channel (ENaC). Here we show that knockout ubiquitin ligase Nedd4L (Nedd4-2) specifically in lung epithelia (surfactant protein C-expressing type II and Clara cells) causes fibrosis-like disease, with airway mucus obstruction, goblet cell hyperplasia, massive inflammation, fibrosis, death three weeks age....
Significance Neurons develop processes called neurites to form defined networks. Neurite growth is regulated by many intracellular signaling pathways, among which via phosphatase and tensin homolog (PTEN) of particular relevance because it controls the translation a substantial subset mRNAs that encode proteins with role in neurite growth. Previous studies indicated E3 ubiquitin ligases Nedd4-1 Nedd4-2 may ubiquitinate negatively regulate PTEN various cell types, including Xenopus laevis...
Erythropoietin (EPO) exerts potent neuroprotective, neuroregenerative and procognitive functions. However, unequivocal demonstration of erythropoietin receptor (EPOR) expression in brain cells has remained difficult since previously available anti-EPOR antibodies (EPOR-AB) were unspecific. We report here a new, highly specific, polyclonal rabbit EPOR-AB directed against different epitopes the cytoplasmic tail human murine EPOR its characterization by mass spectrometric analysis...
Beyond its role in parturition and lactation, oxytocin influences higher brain processes that control social behavior of mammals, perturbed signaling has been linked to the pathogenesis several psychiatric disorders. However, it is still largely unknown how exactly regulates neuronal function. We show early, transient exposure vitro inhibits development hippocampal glutamatergic neurons, leading reduced dendrite complexity, synapse density, excitatory transmission, while sparing GABAergic...
The E3 ubiquitin ligase NEDD4 has been intensively studied in processes involved viral infections, such as virus budding. However, little is known about its functions bacterial infections. Our investigations into the role of intracellular infections demonstrate that Mycobacterium tuberculosis and Listeria monocytogenes, but not bovis BCG, replicate more efficiently knockdown macrophages. In parallel, or knockout impaired basal macroautophagy/autophagy, well infection-induced autophagy....
Transmitter release at synapses between nerve cells is spatially restricted to active zones, where synaptic vesicle docking, priming, and Ca2+-dependent fusion take place in a temporally highly coordinated manner. Munc13s are essential for priming vesicles competent state, their specific zone localization contributes the restriction of transmitter speed excitation-secretion coupling. However, molecular mechanism recruitment not known. We show here that Munc13 isoforms Munc13-1 ubMunc13-2...
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,...
Skeletal muscle atrophy is a consequence of inactivity resulting from denervation, unloading and immobility. It accompanies many chronic disease states also occurs as pathophysiologic normal aging. In all these conditions, ubiquitin-dependent proteolysis key regulator the loss mass, ubiquitin ligases confer specificity to this process by interacting with, linking moieties target substrates through protein∶protein interaction domains. Our previous work suggested that ubiquitin-protein ligase...
Significance Brain function requires high-fidelity transmission of information between individual brain cells at synapses, physical contacts that contain a specialized machinery for passing and receiving signals. Synaptic cell adhesion proteins form bridges neurons are critical fine-tuning synaptic properties. Because their roles in transmission, mutations these contribute to wide range neuropsychiatric diseases. Here, we study the role two proteins, LRRTM1 LRRTM2, signaling excitatory...
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%...