A5103085177- Autoimmune Neurological Disorders and Treatments
- Cellular transport and secretion
- Neuroscience and Neuropharmacology Research
- Genetics and Neurodevelopmental Disorders
- Metal-Catalyzed Oxygenation Mechanisms
- Porphyrin and Phthalocyanine Chemistry
- Cancer, Hypoxia, and Metabolism
- Molecular Junctions and Nanostructures
- Receptor Mechanisms and Signaling
- Lipid Membrane Structure and Behavior
- Enzyme Structure and Function
- Supramolecular Self-Assembly in Materials
- Bacteriophages and microbial interactions
- Metal complexes synthesis and properties
- Surface Chemistry and Catalysis
- Porphyrin Metabolism and Disorders
- Adenosine and Purinergic Signaling
- Protein Kinase Regulation and GTPase Signaling
- CO2 Reduction Techniques and Catalysts
- Hedgehog Signaling Pathway Studies
- RNA and protein synthesis mechanisms
- Sympathectomy and Hyperhidrosis Treatments
- Hearing, Cochlea, Tinnitus, Genetics
- Neuroscience and Neural Engineering
- Biochemical and Structural Characterization
Nagoya University
2006-2025
National Institute for Physiological Sciences
2013-2022
The Graduate University for Advanced Studies, SOKENDAI
2013-2022
National Institutes of Natural Sciences
2014-2022
Department of Physiological Sciences
2020-2021
More than 30 mutations in LGI1, a secreted neuronal protein, have been reported with autosomal dominant lateral temporal lobe epilepsy (ADLTE). Although LGI1 haploinsufficiency is thought to cause ADLTE, the underlying molecular mechanism that results abnormal brain excitability remains mysterious. Here, we focused on mode of action autoantibodies associated limbic encephalitis (LE), which one acquired epileptic disorders characterized by subacute onset amnesia and seizures. We...
Epilepsy is a devastating and poorly understood disease. Mutations in secreted neuronal protein, leucine-rich glioma inactivated 1 (LGI1), were reported patients with an inherited form of human epilepsy, autosomal dominant partial epilepsy auditory features (ADPEAF). Here, we report essential role LGI1 as antiepileptogenic ligand. We find that loss mice (LGI1(-/-)) causes lethal which specifically rescued by the expression transgene, but not LGI3. Moreover, heterozygous for mutation...
Postsynaptic density (PSD)-95, the most abundant postsynaptic scaffolding protein, plays a pivotal role in synapse development and function. Continuous palmitoylation cycles on PSD-95 are essential for its synaptic clustering regulation of AMPA receptor However, molecular mechanisms palmitate cycling remain incompletely understood, as depalmitoylating enzymes unknown. Here, we isolated 38 mouse or rat serine hydrolases found that subset specifically depalmitoylated heterologous cells. These...
Autoimmune forms of encephalitis have been associated with autoantibodies against synaptic cell surface antigens such as NMDA- and AMPA-type glutamate receptors, GABA<sub>B</sub> receptor, LGI1. However, it remains unclear how many autoantigens are yet to be defined. Using immunoproteomics, we identified the GABA<sub>A</sub> receptor in human sera from two patients diagnosed who presented cognitive impairment multifocal brain MRI abnormalities. Both had antibodies directed extracellular...
Epilepsy is a common brain disorder throughout history. Epilepsy-related ligand-receptor complex, LGI1-ADAM22, regulates synaptic transmission and has emerged as determinant of excitability, their mutations acquired LGI1 autoantibodies cause epileptic disorders in human. Here, we report the crystal structure human LGI1-ADAM22 revealing 2:2 heterotetrameric assembly. The hydrophobic pocket C-terminal epitempin-repeat (EPTP) domain binds to metalloprotease-like ADAM22. N-terminal leucine-rich...
Sensorineural hearing loss causes cell death in central auditory neurons, but molecular mechanisms of triggering this process are not fully understood. We report here that afferent activity promotes by facilitating proBDNF-p75NTR signals cochlear nucleus chicks around hatch. RNA-seq analyses revealed up-regulation genes related to proBDNF-p75NTR-JNK as well apoptosis at the within 24hours after unilateral cochlea deprivation. Western blotting confirmed a high level proBDNF protein nucleus....
The synthesis of a robust bio-nanotube consisting the β-helical tubular component proteins bacteriophage T4 is described. crystal structure indicates that it has well-defined nanoscale length 10 nm as result head-to-head dimerization β-helices. Surprisingly, tube assembly high thermal stability, tolerance to organic solvents, and wide pH-stability range. Detailed facts importance specialist readers are published ”Supporting Information”. Such documents peer-reviewed, but not copy-edited or...
We have constructed a robust β-helical nanotube from the component proteins of bacteriophage T4 and modified this with RuII(bpy)3 ReI(bpy)(CO)3Cl complexes. The photocatalytic system arranged on tube catalyzes reduction CO2 higher reactivity than that mixture monomeric forms.
Protein-to-protein electron transfer (ET) is a critical process in biological chemistry for which fundamental understanding expected to provide wealth of applications biotechnology. Investigations protein-protein ET systems reductive activation artificial cofactors introduced into proteins remains particularly challenging because the complexity interactions between cofactor and system contributing ET. In this work, we construct an system, using heme oxygenase (HO), known catalyze conversion...
What percentage of the protein function is required to prevent disease symptoms a fundamental question in genetic disorders. Decreased transsynaptic LGI1-ADAM22 complexes, because their mutations or autoantibodies, cause epilepsy and amnesia. However, it remains unclear how levels are regulated much required. Here, by structural analysis, we demonstrate that quantitative dual phosphorylation ADAM22 kinase A (PKA) mediates high-affinity binding dimerized 14-3-3. This interaction protects from...
The small GTPase Cdc42 exists in the form of two alternatively spliced variants that are modified by hydrophobic chains: ubiquitously expressed Cdc42-prenyl and a brain-specific isoform can be palmitoylated, Cdc42-palm. Our previous work demonstrated Cdc42-palm palmitoylated at cysteine residues, Cys188 Cys189, while also prenylated. We showed palmitoylation is essential for plasma membrane localization critically involved Cdc42-mediated regulation gene transcription neuronal morphology....
A bionanocup chemical reactor is constructed from a heteroprotein assembly bacteriophage T4. The preparation of stable iron(III) porphyrin–bionanocup composite described. hydrophobic cup provides space suitable for the fixation low-water-solubility porphyrins. application composites catalysis sulfoxidation thioanisoles demonstrated (see figure).
We have succeeded in improving the stability of Fe(Schiff-base).heme oxygenase (HO) hybrids by ligand design based on crystal structure Fe(N,N'-bis(salicylidene)-3.4-diaminobenzene propionic acid).HO.