A5079061263- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Hearing, Cochlea, Tinnitus, Genetics
- Protein Kinase Regulation and GTPase Signaling
- Cellular transport and secretion
- Receptor Mechanisms and Signaling
- Nitric Oxide and Endothelin Effects
- Cell Adhesion Molecules Research
- Neuroscience and Neuropharmacology Research
- Mitochondrial Function and Pathology
- Vestibular and auditory disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Cardiac Arrhythmias and Treatments
- Atrial Fibrillation Management and Outcomes
- Endoplasmic Reticulum Stress and Disease
- Intracranial Aneurysms: Treatment and Complications
- Adenosine and Purinergic Signaling
- Genetic Neurodegenerative Diseases
- Robotics and Sensor-Based Localization
- Phagocytosis and Immune Regulation
- Pituitary Gland Disorders and Treatments
- Glycosylation and Glycoproteins Research
- Aortic aneurysm repair treatments
- Ion channel regulation and function
- Cellular Mechanics and Interactions
- Lipid Membrane Structure and Behavior
Kobe University
2016-2025
Yamaguchi University
2006-2020
Laboratory of Molecular Genetics
2018
Denso (United States)
2003-2016
Hyogo Medical University
2009
National Institute of Allergy and Infectious Diseases
2006
National Institutes of Health
2006
Denso (Japan)
2002-2003
Kanazawa Hospital
2001
Hitachi (Japan)
1996
Several Nox family NADPH oxidases function as multicomponent enzyme systems. We explored determinants of assembly the Nox1 and Nox3 examined involvement Rac1 in their regulation. Both enzymes are supported by p47phox p67phox or homologous regulators called Noxo1 Noxa1, although is less dependent on these cofactors for activity. Plasma membrane targeting Noxa1 depends Noxo1, through tail-to-tail interactions between proteins. can support without when targeted to plasma fusing membrane-binding...
Dual oxidases (Duox1 and Duox2) are plasma membrane-targeted hydrogen peroxide generators that support extracellular hemoperoxidases. Duox activator 2 (Duoxa2), initially described as an endoplasmic reticulum resident protein, functions a maturation factor needed to deliver active Duox2 the cell surface. However, less is known about Duox1/Duoxa1 homologues. We identified four alternatively spliced Duoxa1 variants explored their roles in subcellular targeting reconstitution. Duox1...
Ca(2+) signals through store-operated (SOC) channels, activated by the depletion of from endoplasmic reticulum, regulate various physiological events. Orai1 is pore-forming subunit release-activated (CRAC) channel, best characterized SOC channel. stromal interaction molecule (STIM) 1, a sensor located in reticulum. and STIM1 are crucial for channel activation, but molecular mechanisms regulating function not fully understood. In this study, we demonstrate that protein kinase C (PKC)...
Macrophages and dendritic cells continuously survey their environment in search of foreign particles soluble antigens. Such surveillance involves the ongoing extension actin-rich protrusions consequent formation phagosomes macropinosomes. The signals inducing this constitutive cytoskeletal remodeling have not been defined. We report that, unlike nonphagocytic cells, macrophages immature elevated levels phosphatidic acid (PA) plasma membrane. plasmalemmal PA is synthesized by phosphorylation...
Spinocerebellar ataxia type 14 (SCA14) is an autosomal dominant neurodegenerative disease caused by mutations in protein kinase Cgamma (PKCgamma). Interestingly, 18 of 22 are concentrated the C1 domain, which binds diacylglycerol and necessary for translocation regulation PKCgamma activity. To determine effect these on function pathology SCA14, we investigated enzymological properties mutant PKCgammas. We found that wild-type PKCgamma, but not domain mutants, inhibits Ca2+ influx response to...
When using the median infratentorial supracerebellar approach, all or numerous bridging veins over cerebellar surface must be sacrificed. Such sacrifice potentially causes venous infarction, especially when excessive retraction is applied. To prevent such potential complications, neurosurgeons have adequate knowledge of anatomy veins, particularly hemispheric veins.In 14 cadaveric specimens (26 sides), number, locations, and tributaries both vermian between superior cerebellum tentorium were...
Cdc42 is a key regulator of dynamic actin organization. However, little known about how Cdc42-dependent regulation influences steady-state structures in differentiated epithelia. We employed inner ear hair cell (HC)-specific conditional knockout to analyze the role HCs possessing highly elaborate stable protrusions (stereocilia). Atoh1–Cre;Cdc42flox/flox mice developed normally but progressively degenerated after maturation, resulting progressive hearing loss particularly at high...
Research Article5 October 2016Open Access Source DataTransparent process Constitutive activation of DIA1 (DIAPH1) via C-terminal truncation causes human sensorineural hearing loss Takehiko Ueyama Corresponding Author [email protected] orcid.org/0000-0002-5647-3937 Laboratory Molecular Pharmacology, Biosignal Center, Kobe University, Kobe, Japan Search for more papers by this author Yuzuru Ninoyu orcid.org/0000-0002-9407-4697 Shin-ya Nishio Department Otorhinolaryngology, Shinshu University...
Reactive oxygen species (ROS) produced by NADPH oxidases (Nox) contribute to the development of different types sensorineural hearing loss (SNHL), a common impairment in humans with no established treatment. Although essential role Nox3 otoconia biosynthesis and its possible involvement have been reported rodents, immunohistological methods targeted at detecting expression inner ear cells reveal ambiguous results. Therefore, mechanism underlying Nox3-dependent SNHL remains unclear warrants...
Abstract Postsynaptic proteins play crucial roles in synaptic function and plasticity. During brain development, alterations number, shape, stability occur, known as synapse maturation. However, the postsynaptic protein composition changes during development are not fully understood. Here, we show trajectory of proteome developing male mice common marmosets. Proteomic analysis at 2, 3, 6, 12 weeks age shows that involved synaptogenesis differentially expressed this period. Analysis published...
At least 10% of proteins constituting the human proteome are subject to S-acylation by a long-chain fatty acid, thioesterified Cys thiol side chain. Fatty (prototypically, S-palmitoylation) operates across eukaryotic phylogeny and cell type. S-palmitoylation is carried out in mammalian cells family 23-24 dedicated zDHHC palmitoyl transferase enzymes, mutation zDHHCs associated with number pathophysiologies. Activation auto-S-palmitoylation, transthioesterification active site acyl-CoA,...
Abstract DFNA1 (deafness, nonsyndromic autosomal dominant 1), initially identified as sensorineural hearing loss, has been associated with an additional symptom: macrothrombocytopenia. However, the timing of onset loss (HL) and thrombocytopenia not investigated, leaving it unclear which occurs earlier. Here, we generated a knock‐in (KI) mouse model, diaphanous‐related formin 1 ( DIA1 ) KIΔv3/KIΔv3 , in Aequorea coerulescens green fluorescent protein AcGFP ‐ tagged human DIA1(p.R1213X) was...
Protein kinase C (PKC) plays a prominent role in immune signaling, and the paradigms for isoform selective signaling are beginning to be elucidated. Real-time microscopy was combined with molecular biochemical approaches demonstrate PKC-ε Fcγ receptor (FcγR)–dependent phagocytosis. RAW 264.7 macrophages were transfected GFP-conjugated PKC isoforms, GFP movement followed during phagocytosis of fluorescent IgG–opsonized beads. PKC-ε, but not PKC-δ, concentrated around accumulation transient;...
In the phagocytic cell, NADPH oxidase (Nox2) system, cytoplasmic regulators (p47 phox , p67 p40 and Rac) translocate associate with membrane-spanning flavocytochrome b 558 leading to activation of superoxide production. We examined membrane targeting proteins explored conformational changes in that regulate its translocation membranes upon stimulation. GFP-p40 translocates early endosomes, whereas GFP-p47 plasma response arachidonic acid. contrast, GFP-p67 does not when expressed alone, but...
Abstract We engineered a method for detecting intramolecular and intermolecular phox protein interactions in cells by fluorescence microscopy using fusion proteins of complementary fragments coral fluorescent reporter (monomeric Kusabira-Green). confirmed the efficacy monomeric Kusabira-Green system showing that PX PB1 domains p40phox interact intact cells, which we suggested maintains this an inactive closed conformation. Using system, also explored within p47phox showed domain interacts...
The involvement of phospholipase D (PLD) in the regulation melanogenesis was examined. Treatment B16 mouse melanoma cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted activation PLD and a decrease melanin content. 1-Butanol, but not 2-butanol, completely blocked TPA-induced inhibition melanogenesis, suggesting this event. Reverse transcription-PCR immunoblot analyses revealed existence both isozymes, PLD1 PLD2, cells. When or PLD2 introduced into those by an adenoviral...
Abstract Protein kinase C (PKC) plays a prominent role in immune signaling. To elucidate the signal transduction respiratory burst and isoform-specific function of PKC during FcγR-mediated phagocytosis, we used live, digital fluorescence imaging mouse microglial cells expressing GFP-tagged molecules. βI PKC, εPKC, diacylglycerol (DGK) β dynamically transiently accumulated around IgG-opsonized beads (BIgG). Moreover, accumulation p47phox, an essential cytosolic component NADPH oxidase...
It is commonly assumed that all phagosomes have identical molecular composition. This assumption has remained largely unchallenged due to a paucity of methods distinguish individual phagosomes. We devised an assay extends the utility nitro blue tetrazolium for detection and quantification NAPDH oxidase (NOX) activity in Implementation this revealed murine macrophages there heterogeneity ability generate superoxide, both between within cells. To elucidate basis variability NOX activation, we...
Considerable evidence of reactive oxygen species (ROS) involvement in cochlear hair cell (HC) loss, leading to acquired sensorineural hearing loss (SNHL), were reported. Cochlear synaptopathy between HCs and spiral ganglion neurons has been gathering attention as a HC precursor not detectable by normal auditory evaluation. However, the molecular mechanisms linking ROS with well relationship have elucidated. Here, we examined these linkages using NOX4-TG mice, which constitutively produce...