Papers - Oka, Kotaro

Magnesium Is a Key Player in Neuronal Maturation and Neuropathology.

Yamanaka R, Shindo Y, Oka K

International journal of molecular sciences. (International Journal of Molecular Sciences)  20 ( 14(3439) )  2019.07

Research paper (scientific journal), Joint Work, Accepted,  ISSN  16616596

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Magnesium (Mg) is the second most abundant cation in mammalian cells, and it is essential for numerous cellular processes including enzymatic reactions, ion channel functions, metabolic cycles, cellular signaling, and DNA/RNA stabilities. Because of the versatile and universal nature of Mg2+, the homeostasis of intracellular Mg2+ is physiologically linked to growth, proliferation, differentiation, energy metabolism, and death of cells. On the cellular and tissue levels, maintaining Mg2+ within optimal levels according to the biological context, such as cell types, developmental stages, extracellular environments, and pathophysiological conditions, is crucial for development, normal functions, and diseases. Hence, Mg2+ is pathologically involved in cancers, diabetes, and neurodegenerative diseases, such as Parkinson’s disease, Alzheimer’s disease, and demyelination. In the research field regarding the roles and mechanisms of Mg2+ regulation, numerous controversies caused by its versatility and complexity still exist. As Mg2+, at least, plays critical roles in neuronal development, healthy normal functions, and diseases, appropriate Mg2+ supplementation exhibits neurotrophic effects in a majority of cases. Hence, the control of Mg2+ homeostasis can be a candidate for therapeutic targets in neuronal diseases. In this review, recent results regarding the roles of intracellular Mg2+ and its regulatory system in determining the cell phenotype, fate, and diseases in the nervous system are summarized, and an overview of the comprehensive roles of Mg2+ is provided.

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Stochastic thermodynamic limit on E. coli adaptation by information geometric approach.

Ashida K, Oka K

Biochemical and biophysical research communications. (Biochemical and Biophysical Research Communications)  15 ( 508(3) ) 690 - 694 2018.12

Research paper (scientific journal), Joint Work, Accepted,  ISSN  0006291X

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Biological systems process information under noisy environment. Sensory adaptation model of E. coli is suitable for investigation because of its simplicity. To understand the adaptation processing quantitatively, stochastic thermodynamic approach has been attempted. Information processing can be assumed as state transition of a system that consists of signal transduction molecules using thermodynamic approach, and efficiency can be measured as thermodynamic cost. Recently, using information geometry and stochastic thermodynamics, a relationship between speed of the transition and the thermodynamic cost has been investigated for a chemical reaction model. Here, we introduce this approach to sensory adaptation model of E. coli, and examined a relationship between adaptation speed and the thermodynamic cost, and efficiency of the adaptation speed. For increasing external noise level in stimulation, the efficiency decreased, but the efficiency was highly robust to external stimulation strength. Moreover, we demonstrated that there is the best noise to achieve the adaptation in the aspect of thermodynamic efficiency. Our quantification method provides a framework to understand the adaptation speed and the thermodynamic cost for various biological systems.

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GABA-Induced Intracellular Mg²⁺ Mobilization Integrates and Coordinates Cellular Information Processing for the Maturation of Neural Networks.

Yamanaka R, Shindo Y, Hotta K, Suzuki K, Oka K

Current biology (Current Biology)  28 ( 24 ) 3984 - 3991 2018.11

Research paper (scientific journal), Joint Work, Accepted,  ISSN  09609822

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Yamanaka et al. demonstrate that GABA triggers mitochondrial Mg 2+ release in neurons at specifically developmental early stages, and the physiological Mg 2+ redistribution into cytoplasm regulates ERK, CREB, and mTOR activities with target-dependent manners, thereby facilitating neuronal maturation. Mg 2+ is a novel signal transducer.

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14-3-3εa directs the pulsatile transport of basal factors toward the apical domain for lumen growth in tubulogenesis.

Mizotani Y, Suzuki M, Hotta K, Watanabe H, Shiba K, Inaba K, Tashiro E, Oka K, Imoto M

Proceedings of the National Academy of Sciences of the United States of America (Proceedings of the National Academy of Sciences of the United States of America)  115 ( 38 ) E8873 - E8881 2018.09

Research paper (scientific journal), Joint Work, Accepted,  ISSN  00278424

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The Ciona notochord has emerged as a simple and tractable in vivo model for tubulogenesis. Here, using a chemical genetics approach, we identified UTKO1 as a selective small molecule inhibitor of notochord tubulogenesis. We identified 14-3-3ϵa protein as a direct binding partner of UTKO1 and showed that 14-3-3ϵa knockdown leads to failure of notochord tubulogenesis. We found that UTKO1 prevents 14-3-3ϵa from interacting with ezrin/radixin/moesin (ERM), which is required for notochord tubulogenesis, suggesting that interactions between 14-3-3ϵa and ERM play a key role in regulating the early steps of tubulogenesis. Using live imaging, we found that, as lumens begin to open between neighboring cells, 14-3-3ϵa and ERM are highly colocalized at the basal cortex where they undergo cycles of accumulation and disappearance. Interestingly, the disappearance of 14-3-3ϵa and ERM during each cycle is tightly correlated with a transient flow of 14-3-3ϵa, ERM, myosin II, and other cytoplasmic elements from the basal surface toward the lumen-facing apical domain, which is often accompanied by visible changes in lumen architecture. Both pulsatile flow and lumen formation are abolished in larvae treated with UTKO1, in larvae depleted of either 14-3-3ϵa or ERM, or in larvae expressing a truncated form of 14-3-3ϵa that lacks the ability to interact with ERM. These results suggest that 14-3-3ϵa and ERM interact at the basal cortex to direct pulsatile basal accumulation and basal-apical transport of factors that are essential for lumen formation. We propose that similar mechanisms may underlie or may contribute to lumen formation in tubulogenesis in other systems.

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Effect of interactions among individuals on the chemotaxis behaviours of Caenorhabditis elegans

Yoshimizu T, Shidara H, Ashida K, Hotta K, Oka K

The Journal of experimental biology 2018 (Journal of Experimental Biology)  221 ( 11 )  2018.06

Research paper (scientific journal), Joint Work, Accepted,  ISSN  00220949

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In many species, individual social animals interact with others in their group and change their collective behaviours. For the solitary nematode Caenorhabditis elegans strain N2, previous research suggests that individuals can change the behaviour of other worms via pheromones and mechanosensory interactions. In particular, pheromones affect foraging behaviour, so that the chemotactic behaviours of individuals in a group (population) can be modulated by interactions with other individuals in the population. To investigate this, we directly compared the chemotactic behaviours of isolated (single) worms with those of individual animals within a population. We found that worms approached an odour source in a distinct manner depending on whether they were alone or in a population. Analysis of behaviours of the N2 worm and a pheromone production-defective mutant revealed that the 'pirouette' strategy was modulated by interaction of the worms via pheromones. Thus, pheromones play an important role in the characteristic collective behaviours seen in the population condition.

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Transitional correlation between inner-membrane potential and ATP levels of neuronal mitochondria.

Suzuki R, Hotta K, Oka K.

Scientific Reports. (Scientific Reports)  8 ( 1 ) 2993 2018.02

Research paper (scientific journal), Joint Work, Accepted

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The importance of highly active mitochondria and their contribution to neuronal function has been of recent interest. In most cases, however, mitochondrial activity is estimated using measurements of mitochondrial inner membrane potential (IMPmito), and little is known about the dynamics of native mitochondrial ATP (ATPmito). This study conducted simultaneous imaging of IMPmito and ATPmito in neurons to explore their behaviour and their correlation during physiological mitochondrial/neuronal activity. We found that mitochondrial size, transport velocity and transport direction are not dependent on ATPmito or IMPmito. However, changes in ATPmito and IMPmito during mitochondrial fission/fusion were found; IMPmito depolarized via mitochondrial fission and hyperpolarized via fusion, and ATPmito levels increased after fusion. Because the density of mitochondria is higher in growth cones (GCs) than in axonal processes, integrated ATPmito signals (density × ATPmito) were higher in GCs. This integrated signal in GCs correlated with axonal elongation. However, while the averaged IMPmito was relatively hyperpolarized in GCs, there was no correlation between IMPmito in GCs and axonal elongation. A detailed time-course analysis performed to clarify the reason for these discrepancies showed that IMPmito and ATPmito levels did not always correlate accurately; rather, there were several correlation patterns that changed over time.

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A Transient Rise in Free Mg²⁺ Ions Released from ATP-Mg Hydrolysis Contributes to Mitotic Chromosome Condensation.

Maeshima K, Matsuda T, Shindo Y, Imamura H, Tamura S, Imai R, Kawakami S, Nagashima R, Soga T, Noji H, Oka K, Nagai T.

Curr Biol. 28 ( 3 ) 444 - 451 2018.02

Research paper (scientific journal), Joint Work, Accepted

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A Transient Rise in Free Mg²⁺ Ions Released from ATP-Mg Hydrolysis Contributes to Mitotic Chromosome Condensation

Maeshima K., Matsuda T., Shindo Y., Imamura H., Tamura S., Imai R., Kawakami S., Nagashima R., Soga T., Noji H., Oka K., Nagai T.

Current Biology (Current Biology)  28 ( 3 ) 444 - 451.e6 2018.02

ISSN  09609822

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For cell division, negatively charged chromatin, in which nucleosome fibers (10 nm fibers) are irregularly folded [1–5], must be condensed into chromosomes and segregated. While condensin and other proteins are critical for organizing chromatin into the appropriate chromosome shape [6–17], free divalent cations such as Mg2+ and Ca2+, which condense chromatin or chromosomes in vitro [18–28], have long been considered important, especially for local condensation, because the nucleosome fiber has a net negative charge and is by itself stretched like “beads on a string” by electrostatic repulsion. For further folding, other positively charged factors are required to decrease the charge and repulsion [29]. However, technical limitations to measure intracellular free divalent cations, but not total cations [30], especially Mg2+, have prevented us from elucidating their function. Here, we developed a Förster resonance energy transfer (FRET)-based Mg2+ indicator that monitors free Mg2+ dynamics throughout the cell cycle. By combining this indicator with Ca2+ [31] and adenosine triphosphate (ATP) [32] indicators, we demonstrate that the levels of free Mg2+, but not Ca2+, increase during mitosis. The Mg2+ increase is coupled with a decrease in ATP, which is normally bound to Mg2+ in the cell [33]. ATP inhibited Mg2+-dependent chromatin condensation in vitro. Chelating Mg2+ induced mitotic cell arrest and chromosome decondensation, while ATP reduction had the opposite effect. Our results suggest that ATP-bound Mg2+ is released by ATP hydrolysis and contributes to mitotic chromosome condensation with increased rigidity, suggesting a novel regulatory mechanism for higher-order chromatin organization by the intracellular Mg2+-ATP balance. How the negatively charged long genomic DNA is organized into mitotic chromosome remains unclear. Using a newly developed Mg2+ indicator, Maeshima et al. demonstrate a transient rise in free Mg2+ released from ATP-Mg during mitosis and suggest that the rise contributes to mitotic chromosome condensation by charge neutralization.

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Highly sensitive bioluminescent probe for thiol detection in living cells.

Hemmi M, Ikeda Y, Shindo Y, Nakajima T, Nishiyama S, Oka K, Sato M, Hiruta Y, Citterio D, Suzuki K.

Chem Asian J.2017 (Chemistry - An Asian Journal)  13 ( 6 ) 648 - 655 2018.01

Research paper (scientific journal), Joint Work, Accepted,  ISSN  18614728

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The sensitive detection of thiols including glutathione and cysteine is desirable owing to their roles as indispensable biomolecules in maintaining intracellular biological redox homeostasis. Herein, we report the design and synthesis of SEluc-1 (sulfinate ester luciferin), a chemoselective probe exhibiting a ratiometric and turn-on response towards thiols selectively in fluorescence and bioluminescence, respectively. The probe, which was designed based on the “caged” luciferin strategy, displays excellent selectivity, high signal/noise ratio (>240 in the case of bioluminescence), and a biologically relevant limit of detection (LOD, 80 nm for cysteine), which are all desirable traits for a sensitive bioluminescent sensor. SEluc-1 was further applied to fluorescence imaging of thiol activity in living human cervical cancer HeLa cell cultures, and was successfully able to detect fluctuations in thiol concentrations induced by oxidative stress in a bioluminescent assay utilizing African green monkey fibroblast COS-7 cells and human breast adenocarcinoma MCF-7 cells.

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Characterization of calcium transients during early embryogenesis in ascidians Ciona robusta (Ciona intestinalis type A) and Ciona savignyi.

Akahoshi T, Hotta K, Oka K.

Developmental biology. 431 ( 2 ) 205 - 214 2017.11

Research paper (scientific journal), Joint Work, Accepted

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Compartmentalized cGMP Responses of Olfactory Sensory Neurons in Caenorhabditis elegans

Shidara H, Hotta K, Oka K.

The Journal of neuroscience. 37 ( 14 ) 3753 - 3763 2017.04

Research paper (scientific journal), Joint Work, Accepted

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Mitochondrial Mg²⁺ homeostasis decides cellular energy metabolism and vulnerability to stress

Yamanaka R, Tabata S, Shindo Y, Hotta K, Suzuki K, Soga T, Oka K

Scientific Reports 6 ( 30027 )  2016.07

Research paper (scientific journal), Joint Work, Accepted

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An Artificial Reaction Promoter Modulates Mitochondrial Functions via Chemically Promoting Protein Acetylation

Shindo Y, Komatsu H, Hotta K, Ariga K, Oka K

Scientific Reports 6 ( 29224 )  2016.07

Research paper (scientific journal), Joint Work, Accepted

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Altered expression of Mg²⁺ transport proteins during Parkinson's disease-like dopaminergic cell degeneration in PC12 cells

Shindo Y, Yamanaka R, Suzuki K, Hotta K, Oka K

Biochim Biophys Acta 1863 ( 8 ) 1979 - 1984 2016.05

Research paper (scientific journal), Joint Work

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Qualitative and quantitative estimation of comprehensive synaptic connectivity in short- and long-term cultured rat hippocampal neurons with new analytical methods inspired by Scatchard and Hill plots.

Tanamoto R., Shindo Y., Niwano M., Matsumoto Y., Miki N., Hotta K., Oka K.

Biochem Biophys Res Commun. 471 ( 4 ) 486 - 491 2016.03

Research paper (scientific journal), Joint Work

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Detection of Temperature Difference in Neuronal Cells.

Tanimoto R., Hiraiwa T., Nakai Y., Shindo Y., <U<Oka K.(/)-#HR, Hiroi N., Funahashi A.

Scientific Reports. 6 ( 22071 )  2016.03

Research paper (scientific journal), Joint Work, Accepted

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Neural depolarization triggers Mg²⁺ influx in rat hippocampal neurons. Neuroscience.

Yamanaka R., Shindo Y., Karube T., Hotta K., Suzuki K., Oka K.

Neuroscience. 310   731 - 741 2015.12

Research paper (scientific journal), Joint Work, Accepted

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Spatiotemporal quantification of subcellular ATP levels in a single HeLa cell during changes in morphology

Suzuki R., Hotta K., Oka K.

Sci Rep. 5 ( 16874 )  2015.11

Research paper (scientific journal), Joint Work, Accepted

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Electrical stimulation of cultured neurons using a simply patterned indium-tin-oxide (ITO) glass electrode.

Tanamoto R., Shindo Y., Miki N., Matsumoto Y., Hotta K., Oka K.

Juournal of Nuroscience Methods. 253   272 - 278 2015.09

Research paper (scientific journal), Joint Work, Accepted

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Intracellular magnesium level determines cell viability in the MPP⁺ model of Parkinson's disease.

Shindo Y., Yamanaka R., Suzuki K., Hotta K., Oka K.

Biochim Biophys Acta. 1853 ( 12 ) 3182 - 3191 2015.08

Research paper (scientific journal), Joint Work, Accepted

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