Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society (ACS)  

DOI： 10.1021/jacsau.4c01189

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Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society (ACS)  

DOI： 10.1021/acssensors.4c01800

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Language：English  

DOI： 10.51094/jxiv.967

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Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society (ACS)  

DOI： 10.1021/acssynbio.4c00209

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Language：English   Publishing type：Research paper (scientific journal)  

Hepatocytes can switch their metabolic processes in response to nutrient availability. However, the dynamics of metabolites (such as lactate, pyruvate, and ATP) in hepatocytes during the metabolic switch remain unknown. In this study, we visualized metabolite dynamics in primary cultured hepatocytes during recovery from glucose-deprivation. We observed a decrease in the mitochondrial ATP concentration when glucose was administered to hepatocytes under glucose-deprivation conditions. In contrast, there was slight change in the cytoplasmic ATP concentration. A decrease in mitochondrial ATP concentration was associated with increased protein synthesis rather than glycogen synthesis, activation of urea cycle, and production of reactive oxygen species. These results suggest that mitochondrial ATP is important in switching metabolic processes in the hepatocytes.

DOI： 10.1002/2211-5463.13744

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Biological phenomena are generated by the cooperative and hierarchical relationships between a variety of biomolecules, such as proteins, metabolites, signaling molecules, and ions. In many cases, however, these biomolecules do not have color, and it is difficult to observe them as they are. Therefore, it is necessary to "visualize" each molecule with color or fluorescence, and to analyze the functional relationships between them. The live cell imaging technology using single fluorescent protein (FP)-based indicators has contributed to the visualization of biomolecules. Single FP-based indicators, which change their fluorescence intensity upon binding to the target molecule, have been revolutionized into multicolor indicators by a series of innovative screening methods. On the other hand, we have established an original screening method using semi-rational molecular design and molecular evolution, and have developed many single FP-based indicators for various molecules such as cAMP and glucose. In this article, we focus on single FP-based indicators and introduce their development strategy and the history of screening method.

DOI： 10.1254/fpj.23067

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Language：English   Publishing type：Research paper (scientific journal)  

The process of glycolysis breaks down glycogen stored in muscles, producing lactate through pyruvate to generate energy. Excess lactate is then released into the bloodstream. When lactate reaches the liver, it is converted to glucose, which muscles utilize as a substrate to generate ATP. Although the biochemical study of lactate metabolism in hepatocytes and skeletal muscle cells has been extensive, the spatial and temporal dynamics of this metabolism in live cells are still unknown. We observed the dynamics of metabolism-related molecules in primary cultured hepatocytes and a skeletal muscle cell line upon lactate overload. Our observations revealed an increase in cytoplasmic pyruvate concentration in hepatocytes, which led to glucose release. Skeletal muscle cells exhibited elevated levels of lactate and pyruvate levels in both the cytoplasm and mitochondrial matrix. However, mitochondrial ATP levels remained unaffected, indicating that the increased lactate can be converted to pyruvate but is unlikely to be utilized for ATP production. The findings suggest that excess lactate in skeletal muscle cells is taken up into mitochondria with little contribution to ATP production. Meanwhile, lactate released into the bloodstream can be converted to glucose in hepatocytes for subsequent utilization in skeletal muscle cells.

DOI： 10.1016/j.bbrc.2023.149416

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

FRET-based sensors are utilized for real-time measurements of cellular tension. However, transfection of the sensor gene shows low efficacy and is only effective for a short period. Reporter mice expressing such sensors have been developed, but sensor fluorescence has not been measured successfully using conventional confocal microscopy. Therefore, methods for spatiotemporal measurement of cellular tension in vivo or ex vivo are still limited. We established a reporter mouse line expressing FRET-based actinin tension sensors consisting of EGFP as the donor and mCherry as the acceptor and whose FRET ratio change is observable with confocal microscopy. Tension-induced changes in FRET signals were monitored in the aorta and tail tendon fascicles, as well as aortic smooth muscle cells isolated from these mice. The pattern of FRET changes was distinctive, depending on tissue type. Indeed, aortic smooth muscle cells exhibit different sensitivity to macroscopic tensile strain in situ and in an isolated state. This mouse strain will enable novel types of biomechanical investigations of cell functions in important physiological events.

DOI： 10.1038/s41598-023-50142-z

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Other Link： https://www.nature.com/articles/s41598-023-50142-z

Language：English  

DOI： 10.51094/jxiv.511

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Publisher：Cold Spring Harbor Laboratory  

The widespread use of fluorescence lifetime imaging microscopy (FLIM) for quantitative imaging is hindered by the limited availability of a FLIM-based genetically encoded indicator using a conventional 488 nm laser. Here, we present qMaLioffG, a single green fluorescent protein FLIM indicator showing a fluorescence lifetime change in ATP concentration within the physiological range. This allows quantitative imaging of endogenous ATP to investigate cellular energy status of different cell types.

DOI： 10.1101/2023.08.29.555275

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Language：English   Publishing type：Research paper (scientific journal)  

Microbial secretory protein expression is widely used for biopharmaceutical protein production. However, establishing genetically modified industrial strains that secrete large amounts of a protein of interest is time-consuming. In this study, a simple and versatile high-throughput screening method for protein-secreting bacterial strains is developed. Different genotype variants induced by mutagens are encapsulated in microemulsions and cultured to secrete proteins inside the emulsions. The secreted protein of interest is detected as a fluorescence signal by the fluorescent immunosensor quenchbody (Q-body), and a cell sorter is used to select emulsions containing improved protein-secreting strains based on the fluorescence intensity. The concept of the screening method is demonstrated by culturing Corynebacterium glutamicum in emulsions and detecting the secreted proteins. Finally, productive strains of fibroblast growth factor 9 (FGF9) are screened, and the FGF9 secretion increased threefold compared to that of parent strain. This screening method can be applied to a wide range of proteins by fusing a small detection tag. This is a highly simple process that requires only the addition of a Q-body to the medium and does not require the addition of any substrates or chemical treatments. Furthermore, this method shortens the development period of industrial strains for biopharmaceutical protein production.

DOI： 10.1002/smll.202207943

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.bios.2022.114793

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Publishing type：Research paper (scientific journal)   Publisher：Royal Society of Chemistry (RSC)  

We developed the coiled Q-probe (CQ-probe), a fluorescent probe containing the coiled-coil peptide pair E4/K4, to convert antibodies into biosensors for homogeneous immunoassays. This probe consists of an antibody-binding protein,...

DOI： 10.1039/d3an01499a

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Publishing type：Research paper (scientific journal)   Publisher：Royal Society of Chemistry (RSC)  

Homogeneous immunosensors integrate the advantages of both biosensors and immunoassays; it includes speed, high sensitivity, and accuracy. They have been developed rapidly in the past few years and offer a...

DOI： 10.1039/d2an01913b

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Publisher：Cold Spring Harbor Laboratory  

Abstract

Stimulus-secretion coupling of glucagon-like peptide-1 (GLP-1) from enteroendocrine L cells is important for glucose homeostasis. Although intracellular second messengers including Ca²⁺ and cAMP, and cellular structures including actin cytoskeleton play roles in induction of exocytosis of GLP-1 granules, little is known about the specific part in the process of exocytosis in which they are involved. Here we explored the role of those molecules by live-cell imaging with mouse L cell line GLUTag cells, and used two stimuli: deoxycholic acid (DCA) and high K⁺. DCA increased both intracellular Ca²⁺ and cAMP levels, while high K⁺ only increased Ca²⁺. We next monitored a single exocytosis of GLP-1 granules and found that, during the first 10 minutes of stimulation, both stimuli mainly induced the exocytosis from the predocked granules with the plasma membrane before stimulation or granules immediately fused to the plasma membrane without docking. Furthermore, inhibition of actin polymerization suppressed the proportion of exocytosis by the predocked granules. These results suggest that the exocytotic process of GLP-1 granules is determined by interaction with F-actin upon the increase of either Ca²⁺ or cAMP.

Summary statement

Exocytotic process of glucagon-like peptide-1 granules from a mouse enteroendocrine L cell line is regulated by actin polymerization immediately after elevation of intracellular Ca²⁺ or cAMP levels.

DOI： 10.1101/2022.09.14.508035

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

Cyclic guanosine 3′, 5′-monophosphate (cGMP) is a second messenger that regulates a variety of physiological processes. Here, we develop a red fluorescent protein-based cGMP indicator, “Red cGull”. The fluorescence intensity of Red cGull increase more than sixfold in response to cGMP. The features of this indicator include an EC₅₀ of 0.33 μM for cGMP, an excitation and emission peak at 567 nm and 591 nm, respectively. Live-cell imaging analysis reveal the utility of Red cGull for dual-colour imaging and its ability to be used in conjunction with optogenetics tools. Using enteroendocrine cell lines, Red cGull detects an increase in cGMP following the application of l-arginine. An increase in intracellular cGMP is found to be inhibited by Ca²⁺, and l-arginine-mediated hormone secretion is not potentiated. We propose that Red cGull will facilitate future research in cell signalling in relation to cGMP and its interplay with other signalling molecules.

DOI： 10.1038/s42003-022-03790-2

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Other Link： https://www.nature.com/articles/s42003-022-03790-2

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.2337/db21-0644

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Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society (ACS)  

DOI： 10.1021/acs.biochem.2c00165

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Publisher：Cold Spring Harbor Laboratory  

Thermal engineering at microscale such as the control and measurement of temperature is a key technology in basic biological research and biomaterials development, which remains challenge yet. Here, we engineered the polymeric nanoparticle, in which a fluorescent temperature sensory dye and a photothermal dye were embedded in its polymer matrices, termed nanoHT. When a near infrared laser at 808 nm is illuminated to the particle, it enables to create the subcellular-sized heat spot in a live cell, where fluorescence thermometry allows the read out of the temperature increment concurrently at individual heat spots. Owing to the controlled local heating, we found that the cell death of HeLa cells was induced at the certain temperature at rate of a few seconds. It should be also noted that the cell death was triggered from the very local heat spot at subcellular level. Furthermore, nanoHT was applied for the induction of muscle contraction of the C2C12 myotube by heat. We successfully showed that the heat-induced contraction took place at the limited area of a single myotube according to the alteration of protein-protein interactions related to the contraction event. These studies demonstrated that even a single heat spot provided by a photothermal material could be very effective in altering cellular functions, paving the way for novel photothermal therapies.

DOI： 10.1021/acsnano.2c00285

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Publishing type：Research paper (scientific journal)   Publisher：Royal Society of Chemistry (RSC)  

Antigen tests for SARS-CoV-2 are widely used by the public during the ongoing COVID-19 pandemic, which demonstrates the societal impact of homogeneous immunosensor-related technologies. In this study, we used the...

DOI： 10.1039/d2an01051h

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Publishing type：Research paper (scientific journal)   Publisher：Royal Society of Chemistry (RSC)  

Although intracellular biomarkers can be imaged with fluorescent dye(s)-labeled antibodies, the use of such probes for precise imaging of intracellular biomarkers in living cells remains challenging due to background noise...

DOI： 10.1039/d2sc02355e

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Publisher：Cold Spring Harbor Laboratory  

Thermal engineering at microscale such as the control and measurement of temperature is a key technology in basic biological research and biomaterials development, which remains challenge yet. Here, we engineered the polymeric nanoparticle, in which a fluorescent temperature sensory dye and a photothermal dye were embedded in its polymer matrices, termed nanoHT. When a near infrared laser at 808 nm is illuminated to the particle, it enables to create the subcellular-sized heat spot in a live cell, where fluorescence thermometry allows the read out of the temperature increment concurrently at individual heat spots. Owing to the controlled local heating, we found that the cell death of HeLa cells was induced at the certain temperature at rate of a few seconds. It should be also noted that the cell death was triggered from the very local heat spot at subcellular level. Furthermore, nanoHT was applied for the induction of muscle contraction of the C2C12 myotube by heat. We successfully showed that the heat-induced contraction took place at the limited area of a single myotube according to the alteration of protein-protein interactions related to the contraction event. These studies demonstrated that even a single heat spot provided by a photothermal material could be very effective in altering cellular functions, paving the way for novel photothermal therapies.

DOI： 10.1101/2021.12.19.471878

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Language：English   Publishing type：Research paper (scientific journal)  

Quenchbody (Q-body) is a quench-based fluorescent immunosensor labeled with fluorescent dye(s) near the antigen-binding site of an antibody. Q-bodies can detect a range of target molecules rapidly and directly. However, because Q-bodies show different antigen responses depending on the antibody used, time-consuming optimization of the Q-body structure is often necessary, and a high-throughput screening method for discriminating and selecting good Q-bodies is required. Here, we aimed to develop a molecular display method of nanobody-based "mini Q-bodies" by combining yeast surface display and coiled-coil forming E4/K4 peptide-based fluorescence labeling. As a result, the yeast-displayed mini Q-body recognizing the anti-cancer agent methotrexate (MTX) showed significant quenching and MTX-dependent dequenching on cells. To demonstrate the applicability of the developed method to select highly responsive mini Q-bodies, a small nanobody library consisting of 30 variants that recognize human serum albumin was used as a model. The best variant, showing a 2.4-fold signal increase, was obtained through selection by flow cytometry. Furthermore, the same nanobody prepared from Escherichia coli also worked as a mini Q-body after dye labeling. The described approach will be applied to quickly obtain well-behaved Q-bodies and other fluorescent biosensors for various targets through directed evolutionary approaches.

DOI： 10.1038/s41598-021-02022-7

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Ubiquitin-specific protease 8 (USP8) is a deubiquitinating enzyme involved in multiple membrane trafficking pathways. The enzyme activity is inhibited by binding to 14-3-3 proteins. Mutations in the 14-3-3-binding motif in USP8 are related to Cushing's disease. However, the molecular basis of USP8 activity regulation remains unclear. This study identified amino acids 645-684 of USP8 as an autoinhibitory region, which might interact with the catalytic USP domain, as per the results of pull-down and single-molecule FRET assays performed in this study. In silico modelling indicated that the region forms a WW-like domain structure, plugs the catalytic cleft, and narrows the entrance to the ubiquitin-binding pocket. Furthermore, 14-3-3 inhibited USP8 activity partly by enhancing the interaction between the WW-like and USP domains. These findings provide the molecular basis of USP8 autoinhibition via the WW-like domain. Moreover, they suggest that the release of autoinhibition may underlie Cushing's disease due to USP8 mutations.

DOI： 10.1038/s42003-021-02802-x

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41598-021-02022-7

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DOI： 10.3390/s21154993

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DOI： 10.1039/d1cc02605d

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.chembiol.2021.06.002

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Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society ({ACS})  

DOI： 10.1021/acsomega.0c06281

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Publishing type：Part of collection (book)   Publisher：Springer US  

DOI： 10.1007/978-1-0716-1258-3_9

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Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society ({ACS})  

DOI： 10.1021/acssensors.0c01404

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Language：English   Publishing type：Research paper (scientific journal)  

Glycolysis is the metabolic pathway that converts glucose into pyruvate, whereas fermentation can then produce lactate from pyruvate. Here, we developed single fluorescent protein (FP)-based lactate and pyruvate indicators with low EC50 for trace detection of metabolic molecules and live cell imaging and named them "Green Lindoblum" and "Green Pegassos," respectively. Green Lindoblum (EC50 of 30 µM for lactate) and Green Pegassos (EC50 of 70 µM for pyruvate) produced a 5.2- and 3.3-fold change in fluorescence intensity in response to lactate and pyruvate, respectively. Green Lindoblum measured lactate levels in mouse plasma, and Green Pegassos in combination with D-serine dehydratase successfully estimated D-serine levels released from mouse primary cultured neurons and astrocytes by measuring pyruvate level. Furthermore, live cell imaging analysis revealed their utility for dual-colour imaging, and the interplay between lactate, pyruvate, and Ca2+ in human induced pluripotent stem cell-derived cardiomyocytes. Therefore, Green Lindoblum and Green Pegassos will be useful tools that detect specific molecules in clinical use and monitor the interplay of metabolites and other related molecules in diverse cell types.

DOI： 10.1038/s41598-020-76440-4

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Language：English   Publishing type：Research paper (scientific journal)  

Quenchbody (Q-body) is a fluorescent biosensor in which a fluorescent dye is tagged near the antigen binding site of an antibody. The fluorescence of the dye is quenched by the tryptophan residues present in the variable region of the antibody, and is recovered when the antigen binds. Q-bodies have been prepared using recombinant DNA technology by introducing one or more tag sequence(s) at either the N-terminal of the Fab or the single chain variable region fragment of the antibody, and labeling the tag with a fluorescent dye. However, preparation of recombinant antibody fragments is time-consuming and the performance of the Q-body is unpredictable. Here we report an antibody-binding quenching probe made from protein M from Mycoplasma genitalium that can transform the IgG antibody into an immunosensor. By using bacterially expressed and purified protein M and labeling the C-terminal cysteine-containing tag, we prepared a TAMRA-labeled PM Q-probe. When the Q-probe was incubated with Fab or IgG recognizing the bone Gla protein, the fluorescence of the probe was quenched and subsequently recovered by the adding of antigens in a dose-dependent manner. We also succeeded in detecting several small biomarkers with nanomolar sensitivity, including thyroxine extracted from human serum. The clone found to be suitable for the detection of cortisol was confirmed to work as a recombinant Q-body as well, which also worked in 50% human serum. The results suggest that the Q-probe can quickly convert an IgG to a biosensor, which will be useful in rapid diagnosis of small biomarkers.

DOI： 10.1016/j.bios.2020.112425

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Language：English   Publishing type：Research paper (scientific journal)  

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

DOI： 10.1038/s41467-020-17059-x

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DOI： 10.1021/acssensors.9b02137

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Astrocytes may function as mediators of the impact of noradrenaline on neuronal function. Activation of glial α1-adrenergic receptors triggers rapid astrocytic Ca2+ elevation and facilitates synaptic plasticity, while activation of β-adrenergic receptors elevates cAMP levels and modulates memory consolidation. However, the dynamics of these processes in behaving mice remain unexplored, as do the interactions between the distinct second messenger pathways. Here we simultaneously monitored astrocytic Ca2+ and cAMP and demonstrate that astrocytic second messengers are regulated in a temporally distinct manner. In behaving mice, we found that while an abrupt facial air puff triggered transient increases in noradrenaline release and large cytosolic astrocytic Ca2+ elevations, cAMP changes were not detectable. By contrast, repeated aversive stimuli that lead to prolonged periods of vigilance were accompanied by robust noradrenergic axonal activity and gradual sustained cAMP increases. Our findings suggest distinct astrocytic signaling pathways can integrate noradrenergic activity during vigilance states to mediate distinct functions supporting memory.

DOI： 10.1038/s41467-020-14378-x

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Language：English  

Glucagon-like peptide-1 (GLP-1), secreted by gastrointestinal enteroendocrine L cells, induces insulin secretion and is important for glucose homeostasis. GLP-1 secretion is induced by various luminal nutrients, including amino acids. Intracellular Ca2+ and cAMP dynamics play an important role in GLP-1 secretion regulation; however, several aspects of the underlying mechanism of amino acid-induced GLP-1 secretion are not well characterized. We investigated the mechanisms underlying the L-glutamine-induced increase in Ca2+ and cAMP intracellular concentrations ([Ca2+]i and [cAMP]i, respectively) in murine enteroendocrine L cell line GLUTag cells. Application of L-glutamine to cells under low extracellular Na+ conditions, which inhibited the function of the sodium-coupled L-glutamine transporter, did not induce an increase in [Ca2+]i. Application of G protein-coupled receptor family C group 6 member A and calcium-sensing receptor antagonist showed little effect on [Ca2+]i and [cAMP]i; however, taste receptor type 1 member 3 (TAS1R3) antagonist suppressed the increase in [cAMP]i. To elucidate the function of TAS1R3, which forms a heterodimeric umami receptor with taste receptor type 1 member 1 (TAS1R1), we generated TAS1R1 and TAS1R3 mutant GLUTag cells using the CRISPR/Cas9 system. TAS1R1 mutant GLUTag cells exhibited L-glutamine-induced increase in [cAMP]i, whereas some TAS1R3 mutant GLUTag cells did not exhibit L-glutamine-induced increase in [cAMP]i and GLP-1 secretion. These findings suggest that TAS1R3 is important for L-glutamine-induced increase in [cAMP]i and GLP-1 secretion. Thus, TAS1R3 may be coupled with Gs and related to cAMP regulation.

DOI： 10.1530/JME-19-0260

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DOI： 10.1038/s41598-019-54539-7

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Sonic hedgehog (SHH) is important for organogenesis during development. Recent studies have indicated that SHH is also involved in the proliferation and transformation of astrocytes to the reactive phenotype. However, the mechanisms underlying these are unknown. Involvement of SHH signaling in calcium (Ca) signaling has not been extensively studied. Here, we report that SHH and Smoothened agonist (SAG), an activator of the signaling receptor Smoothened (SMO) in the SHH pathway, activate Ca oscillations in cultured murine hippocampal astrocytes. The response was rapid, on a minute timescale, indicating a non-canonical pathway activity. Pertussis toxin blocked the SAG effect, indicating an involvement of a Gi coupled to SMO. Depletion of extracellular ATP by apyrase, an ATP degrading enzyme, inhibited the SAG-mediated activation of Ca oscillations. These results indicate that SAG increases extracellular ATP levels by activating ATP release from astrocytes, resulting in Ca oscillation activation. We hypothesize that SHH activates SMO-coupled Gi in astrocytes, causing ATP release and activation of Gq/11-coupled P2 receptors on the same cell or surrounding astrocytes. Transcription factor activities are often modulated by Ca patterns; therefore, SHH signaling may trigger changes in astrocytes by activating Ca oscillations. This enhancement of Ca oscillations by SHH signaling may occur in astrocytes in the brain in vivo because we also observed it in hippocampal brain slices. In summary, SHH and SAG enhance Ca oscillations in hippocampal astrocytes, Gi mediates SAG-induced Ca oscillations downstream of SMO, and ATP-permeable channels may promote the ATP release that activates Ca oscillations in astrocytes.

DOI： 10.1074/jbc.RA119.007883

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DOI： 10.1016/j.jbiosc.2019.05.015

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DOI： 10.1021/acs.analchem.9b00447

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DOI： 10.17106/jbr.33.21

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DOI： 10.1002/anie.201804304

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Royal Society of Chemistry  

DOI： 10.1039/c8an90057d

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Language：Japanese   Publisher：(NPO)日本バイオレオロジー学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Royal Society of Chemistry  

DOI： 10.1039/c8an00074c

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Language：Japanese   Publisher：The Japan Society of Mechanical Engineers  

DOI： 10.1299/jsmebio.2018.30.1a03

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Language：Japanese   Publisher：生命科学系学会合同年次大会運営事務局  

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Language：Japanese   Publisher：生命科学系学会合同年次大会運営事務局  

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DOI： 10.1038/s41598-017-07820-6

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DOI： 10.1016/j.molmet.2017.05.013

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DOI： 10.1021/acs.analchem.7b00959

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DOI： 10.1074/jbc.M117.788653

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DOI： 10.1038/s41598-017-00291-9

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DOI： 10.1021/acssensors.6b00582

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Language：Japanese   Publisher：The Japan Society of Mechanical Engineers  

DOI： 10.1299/jsmebio.2017.29.2a46

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Language：Japanese   Publisher：The Japan Society of Mechanical Engineers  

DOI： 10.1299/jsmemecj.2017.s0210202

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DOI： 10.1074/jbc.M116.729863

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DOI： 10.1038/srep28535

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DOI： 10.1039/c5nr08012f

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DOI： 10.1299/jbse.16-00504

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DOI： 10.1530/JOE-15-0090

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DOI： 10.1016/j.bbrc.2015.03.151

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DOI： 10.1371/journal.pone.0100252

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DOI： 10.1016/j.bbrc.2013.07.043

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DOI： 10.1038/nature12037

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DOI： 10.1042/BJ20121022

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DOI： 10.1074/jbc.M112.402677

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DOI： 10.1016/j.bbrc.2012.03.010

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DOI： 10.1002/eji.201141640

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DOI： 10.1042/BJ20091839

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DOI： 10.1091/mbc.E09-08-0722

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DOI： 10.1073/pnas.0906464106

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DOI： 10.1016/j.mod.2009.02.007

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DOI： 10.1126/science.1114110

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DOI： 10.1046/j.1440-169x.2002.00624.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Academic Press Inc.  

DOI： 10.1006/bbrc.1999.1088

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DOI： 10.1016/S0049-3848(97)00123-0

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DOI： 10.1006/bbrc.1997.6554

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DOI： 10.1006/bbrc.1996.0420

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DOI： 10.1016/j.neures.2009.09.1231

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