A5080968511- Cellular transport and secretion
- Pancreatic function and diabetes
- Lipid Membrane Structure and Behavior
- Silicon Nanostructures and Photoluminescence
- Neuroscience and Neuropharmacology Research
- Diabetes Treatment and Management
- Receptor Mechanisms and Signaling
- Semiconductor materials and devices
- Nanowire Synthesis and Applications
- Metabolism, Diabetes, and Cancer
- Advanced Fluorescence Microscopy Techniques
- Calcium signaling and nucleotide metabolism
- Zebrafish Biomedical Research Applications
- Biochemical Analysis and Sensing Techniques
- Erythrocyte Function and Pathophysiology
- Ion channel regulation and function
- Mitochondrial Function and Pathology
- Adipose Tissue and Metabolism
- RNA Interference and Gene Delivery
- Cellular Mechanics and Interactions
- Amino Acid Enzymes and Metabolism
- Diabetes and associated disorders
- Microfluidic and Bio-sensing Technologies
- Neural dynamics and brain function
- CRISPR and Genetic Engineering
The University of Tokyo
2016-2025
Nagoya University
2024
Tokyo University of the Arts
2011-2024
Toyohashi University of Technology
2015
Kyoto University
1998-2013
Nagasaki University
2011
RIKEN Center for Brain Science
2009
Agilent Technologies (Japan)
2009
RIKEN
2005-2007
Kobayashi Pharmaceutical (Japan)
2007
Highlights•Exome sequencing of Japanese ASD trios supports "de novo paradigm"•Integrative analyses were conducted by combining with published DNM data•Integrative confirm and extend ASD-related molecular brain networks•Integrative identify 61 significant genes as well drug candidatesSummaryRecent studies have established important roles de mutations (DNMs) in autism spectrum disorders (ASDs). Here, we analyze DNMs 262 probands origin the paradigm" ASDs across ethnicities. Based on this...
AMP-activated protein kinase (AMPK) has recently been implicated in the control of preproinsulin gene expression pancreatic islet β-cells [da Silva Xavier, Leclerc, Salt, Doiron, Hardie, Kahn and Rutter (2000) Proc. Natl. Acad. Sci. U.S.A. 97, 4023–4028]. Using pharmacological molecular strategies to regulate AMPK activity rat islets clonal MIN6 β-cells, we show here that effects are exerted largely upstream insulin release. Thus forced increases achieved pharmacologically with...
Glucagon-like peptide-1 (GLP-1) is a potent regulator of glucose-stimulated insulin secretion whose mechanisms action are only partly understood. In the present paper, we show that at low (3mM) glucose concentrations, GLP-1 increases free intramitochondrial concentrations both Ca2+ ([Ca2+]m), and ATP ([ATP]m) in clonal MIN6 β-cells. Suggesting cAMP-mediated release from intracellular stores responsible for these effects, [ATP]m were induced by completely blocked Rp isomer...
The molecular mechanisms underlying “kiss and run” or “cavicapture” exocytosis of dense core secretory vesicles are presently unclear. Although dynamin-1 has previously been implicated in the recapture process neurons, recruitment this fission protein to a single exocytosing vesicle not examined real time during peptide release from pancreatic β-cells. Imaged simultaneously clonal insulin-secreting cells by dual color total internal reflection fluorescence microscopy, monomeric red...
Recent studies have suggested that two small GTPases, Rab3A and Rab27A, play a key role in the late steps of dense-core vesicle exocytosis endocrine cells; however, neither precise mechanisms by which these GTPases regulate nor functional relationship between them is clear. In this study, we expressed number different Rab proteins, from Rab1 to Rab41 PC12 cells systematically screened for those are specifically localized on vesicles. We found four Rabs (Rab3A, Rab33A, Rab37) predominantly...
cAMP is a common second messenger that involved in various physiological processes. To expand the colour palette of available indicators, we developed red indicator named "Pink Flamindo" (Pink Fluorescent indicator). The fluorescence intensity Pink Flamindo increases 4.2-fold presence saturating dose cAMP, with excitation and emission peaks at 567 nm 590 nm, respectively. Live-cell imaging revealed effective for monitoring spatio-temporal dynamics intracellular generated by photoactivated...
Adenosine triphosphate (ATP) provides energy for the regulation of multiple cellular processes in living organisms. Capturing spatiotemporal dynamics ATP single cells is fundamental to our understanding mechanisms underlying metabolism. However, it has remained challenging visualize and between distinct intracellular organelles its interplay with other signaling molecules. Using fluorescent proteins, multicolor indicators were developed, enabling simultaneous visualization subcellular...
The role of unconventional myosins in neuroendocrine cells is not fully understood, with involvement suggested the movement both secretory vesicles and mitochondria. Here, we demonstrate colocalization myosin Va (MyoVa) insulin pancreatic beta-cells show that MyoVa copurifies density gradients vesicle marker phogrin-enhanced green fluorescent protein upon fluorescence-activated sorting vesicles. By contrast, immunoreactivity was poorly colocalized mitochondrial or other markers....
Intracellular cAMP and Ca2+ are important second messengers that regulate insulin secretion in pancreatic β-cells; however, the molecular mechanism underlying their mutual interaction for exocytosis is not fully understood. In present study, we investigated interplay between intracellular concentrations ([cAMP]i [Ca2+]i respectively) β-cell line MIN6 using total internal reflection fluorescence microscopy. For measuring [cAMP]i, developed a genetically encoded yellow fluorescent biosensor...
Glucose is the most important energy source for living animals. Here, we developed a series of single fluorescent protein (FP)-based glucose indicators, named as "Green Glifons", to understand hierarchal and mutual relationships between molecules involved in metabolism. Three indicators showed different EC50 (50, 600, 4000 μM), producing ∼7-fold change fluorescence intensity response glucose. The could visualize dynamics cytoplasm, plasma membrane, nucleus mitochondria HeLa cells vivo,...
Rabphilin is a membrane trafficking protein on secretory vesicles that consists of an N-terminal Rab-binding domain and C-terminal tandem C2 domains. The part rabphilin has recently been shown to function as effector for both Rab27A Rab3A in PC12 cells (Fukuda, M., Kanno, E., Yamamoto, A. (2004) J. Biol. Chem. 279, 13065-13075), but the domains during vesicle exocytosis largely unknown. In this study we investigated interaction between SNAREs (soluble N-ethylmaleimide-sensitive factor...
Changes in 5'-AMP-activated protein kinase (AMPK) activity have recently been implicated the control of insulin secretion by glucose (da Silva Xavier, G., Leclerc, I., Varadi, A., Tsuboi, T., Moule, S. K., and Rutter, G. A. (2003) Biochem. J. 371, 761-774). Here, we examine possibility that activation AMPK may regulate distal steps secretion, including vesicle movement fusion with plasma membrane. Vesicle dynamics were imaged single pancreatic MIN6 beta-cells expressing lumen-targeted...
Immersion plating of metals (Ag, Cu, Ni) onto a porous silicon (PS) layer from aqueous and nonaqueous solutions has been studied. The modified PS layers after the immersion were analyzed by X-ray diffraction photoelectron spectroscopy. Fourier transform infrared spectroscopy scanning electron microscopy also performed to investigate structural changes microstructure samples process. In both solutions, deposition metal oxidizes simultaneously different behaviors are discussed in terms rest...
Abstract We systematically synthesized bioluminogenic substrates bearing an amino group on benzothiazole, quinoline, naphthalene, and coumarin scaffolds. They emit bioluminescence in various colors: red, orange, yellow, green. An amino‐substituted coumarylluciferin derivative, coumarylaminoluciferin (CAL), showed the shortest wavelength among reported so far. Further, fluorescence of CAL did not exhibit solvatochromism, which suggests that its is susceptible to environmental factors. applied...
Abstract During embryonic development, physical force plays an important role in morphogenesis and differentiation. Stretch sensitive fluorescence resonance energy transfer (FRET) has the potential to provide non-invasive tension measurements inside living tissue. In this study, we introduced a FRET-based actinin sensor into Xenopus laevis embryos demonstrated that captures variation of across differentiating ectoderm. The sensor, containing mCherry EGFP connected by spider silk protein, was...