A5064601381- Ion Channels and Receptors
- Neurobiology and Insect Physiology Research
- Phytochemicals and Antioxidant Activities
- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Postharvest Quality and Shelf Life Management
- Nicotinic Acetylcholine Receptors Study
- Treatment of Major Depression
- Neuropeptides and Animal Physiology
- Respiratory and Cough-Related Research
- Pain Mechanisms and Treatments
- Bipolar Disorder and Treatment
- Calcium signaling and nucleotide metabolism
- Neurotransmitter Receptor Influence on Behavior
- Pharmacological Effects of Natural Compounds
- Cell Adhesion Molecules Research
- Connexins and lens biology
- Adenosine and Purinergic Signaling
- Vestibular and auditory disorders
- Antibiotic Resistance in Bacteria
- Synthetic Organic Chemistry Methods
- Asymmetric Synthesis and Catalysis
- Stress Responses and Cortisol
- Receptor Mechanisms and Signaling
- Otitis Media and Relapsing Polychondritis
Chubu University
2023-2025
Northwestern University
2015-2024
Kanagawa Children's Medical Center
2019-2024
University of Shizuoka
2016
Toho University
2010
Osaka University of Pharmaceutical Sciences
2008
Osaka University
1991-2006
Kyushu University
1998-2003
Japan Science and Technology Agency
2002
Kyushu Dental University
2001
ORAI1 is a pore subunit of the store-operated Ca(2+) release-activated (CRAC) channel. To examine physiological consequences deficiency, we generated mice with targeted disruption Orai1 gene. The results immunohistochemical analysis showed that expressed in lymphocytes, skin, and muscle wild-type not Orai1(-/-) mice. inbred C57BL/6 background perinatal lethality, which was overcome by crossing them to outbred ICR were small size, eyelid irritation sporadic hair loss resembling cyclical...
Store-operated Ca2+ entry (SOCE) through release-activated (CRAC) channels is critical for lymphocyte function and immune responses. CRAC are hexamers of ORAI proteins that form the channel pore, but contributions individual homologues to not well understood. Here we show deletion Orai1 reduces, whereas Orai2 increases, SOCE in mouse T cells. These distinct effects due ability ORAI2 heteromeric with ORAI1 attenuate function. The combined abolishes strongly impairs cell In vivo, Orai1/Orai2...
Ca(2+) entry through store-operated release-activated (CRAC) channels initiates key functions such as gene expression and exocytosis of inflammatory mediators. Activation CRAC by store depletion involves the redistribution ER sensor, stromal interaction molecule 1 (STIM1), to peripheral sites where it co-clusters with channel subunit, Orai1. However, how STIM1 communicates subsequent events culminating in opening is unclear. Here, we show that Orai1 occurs parallel a pronounced increase...
CRAC channels generate Ca(2+) signals critical for the activation of immune cells and exhibit an intriguing pore profile distinguished by extremely high selectivity, low Cs(+) permeability, small unitary conductance. To identify ion conduction pathway gain insight into structural bases these permeation characteristics, we introduced cysteine residues in channel subunit, Orai1, probed their accessibility to various thiol-reactive reagents. Our results indicate that architecture is...
Abstract ORAI1 is the pore-forming subunit of Ca2+ release-activated (CRAC) channel, which responsible for store-operated entry in lymphocytes. A role T cell function vivo has been inferred from vitro studies cells human immunodeficient patients with mutations and Orai1−/− mice, but a detailed analysis cell-mediated immune responses mice lacking functional missing. We therefore generated Orai1 knock-in (Orai1KI/KI) expressing nonfunctional ORAI1-R93W protein. Homozygosity equivalent...
Ca(2+) release-activated (CRAC) channels are activated through a mechanism wherein depletion of intracellular calcium stores results in the aggregation stromal interaction molecule 1 (STIM1), endoplasmic reticulum (ER) sensor, and Orai1, CRAC channel protein, at overlapping sites ER plasma membranes (PMs). The redistribution is driven direct STIM1-Orai1 binding, an important event that not only controls gating, but also regulates Orai1 ion selectivity. harbours two STIM1 binding sites, one...
Abstract Store-operated Ca 2+ release-activated (CRAC) channels constitute a major pathway for influx and mediate many essential signalling functions in animal cells, yet how they open remains elusive. Here, we investigate the gating mechanism of human CRAC channel Orai1 by its activator, stromal interacting molecule 1 (STIM1). We find that two rings pore-lining residues, V102 F99, work together to form hydrophobic gate. Mutations these residues polar amino acids produce with leaky gates...
Microglia are important mediators of neuroinflammation, which underlies neuropathic pain. However, the molecular checkpoints controlling microglial reactivity not well-understood. Here, we investigated role Orai1 channels for microglia-mediated neuroinflammation following nerve injury and find that deletion in microglia attenuates Ca 2+ signaling production inflammatory cytokines by proalgesic agonists. Conditional attenuated proliferation dorsal horn, spinal cytokine levels, potentiation...
In this study, we tested the influence of serotonin type 2A, 3A and 3B receptor genes <i>(HTR2A, HTR3A, HTR3B)</i> in addition to a polymorphism promoter region transporter <i>(SERTPR)</i>, investigated different characteristics clinical responses paroxetine fluvoxamine. A total 100 Japanese patients affected by major recurrent depression were enrolled randomized 6-week study. The response was evaluated using Hamilton Rating Scale for Depression (HAM-D), adverse drug...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAbsolute stereostructure of swinholide A, a potent cytotoxic macrolide from the Okinawan marine sponge Theonella swinhoeiIsao Kitagawa, Motomasa Kobayashi, Taketo Katori, Megumi Yamashita, Junichi Tanaka, Mitsunobu Doi, and Toshimasa IshidaCite this: J. Am. Chem. Soc. 1990, 112, 9, 3710–3712Publication Date (Print):April 1, 1990Publication History Published online1 May 2002Published inissue 1 April...
Ca(2+) entry through store-operated release-activated (CRAC) channels is an essential trigger for lymphocyte activation and proliferation. The recent identification of Orai1 as a key CRAC channel pore subunit paves the way understanding molecular basis selectivity, ion permeation, regulation channels. Previous mutagenesis studies have indicated that set conserved acidic amino acids in trans membrane domains I III I-II loop (E106, E190, D110, D112, D114) are channel's high selectivity. To...
Abstract Variability in antidepressant response is due to genetic and environmental factors. Among factors, the ones controlling for availability of drug at target site are interesting candidates. Rs6295C/G SNP 5‐HT1A gene (HTR1A) has been found affect expression function HTR1A. In fact rs6295C/G strong linkage disequilibrium with other polymorphisms HTR1A suggesting that those functional effects could be associated than or together synonymous rs6295C/G. present study we examined possible...
Abstract TCR stimulation triggers Ca 2+ signals that are critical for T cell function and immunity. Several pore-forming α auxiliary β subunits of voltage-gated channels (VGCC) were reported in cells, but their mechanism activation remains elusive contribution to signaling cells is controversial. We here identify V β1, encoded by Cacnb1 , as a regulator function. deletion enhances apoptosis impairs the clonal expansion after lymphocytic choriomeningitis virus (LCMV) infection. By contrast,...
Significance Store-operated Orai1 channels mediate transcriptional, proliferative, and effector-cell programs in many cells. Mutations that block channel activation or evoke constitutive activity are known to cause debilitating diseases humans such as immunodeficiency, autoimmunity, myopathy, thrombocytopenia. However, our understanding of the underlying molecular mechanisms these is limited by fundamental gaps how gated. Here, we map key functional interactions between transmembrane domains...
The G-protein-coupled protease-activated receptor 2 (PAR2) plays an important role in the pathogenesis of various inflammatory and auto-immune disorders. In airway epithelial cells (AECs), stimulation PAR2 by allergens proteases triggers release a host mediators to regulate bronchomotor tone immune cell recruitment. Activation turns on several signaling pathways which mobilization cytosolic Ca(2+) is likely critical but poorly understood event. this study, we show that release-activated...
The effects of ethanol on the GABA<sub>A</sub> receptors, which are regarded as one most important target sites ethanol, very controversial, ranging from potentiation to no effect. δ subunit-containing receptors expressed in <i>Xenopus</i> oocytes were recently reported be potently augmented by ethanol. We performed patch-clamp experiments using cerebellar granule cells and mammalian expressing recombinant receptors. In cells, sensitivity GABA increased 7 11 days vitro. Furosemide, an...
A potent cytotoxic dimeric macrolide, swinholide (1), was isolated from the Okinawan marine sponge Theonella swinhoei. The absolute stereostructure of 1, having a dilactone structure with 44-membered ring, has been determined on basis its chemical behavior and an X-ray crystallographic analysis.
The increased production of proinflammatory cytokines by adipose tissue macrophages (ATMs) contributes to chronic, low-level inflammation during obesity. We found that obesity in mice reduced the bioavailability gaseous signaling molecule hydrogen sulfide (H2S). Steady-state, intracellular concentrations H2S were lower ATMs isolated from with diet-induced than lean mice. In addition, concentration macrophage cell line RAW264.7 was an acute inflammatory response evoked microbial product...
Store-operated CRAC channels regulate a wide range of cellular functions including gene expression, chemotaxis, and proliferation. consist two components: the Orai proteins (Orai1-3), which form ion-selective pore, STIM (STIM1-2), endoplasmic reticulum (ER) Ca2+ sensors. Activation is initiated by migration STIM1 to ER-plasma membrane (PM) junctions, where it directly interacts with Orai1 open Ca2+-selective pores channels. The recent elucidation Drosophila structure revealed hexameric...