Publications by authors named "Katsuhiko Mikoshiba"

The mechanisms underlying individual differences in core body temperature (T) are unexplained by genetic factors and poorly understood. Here, we investigated whether the environmental temperature during early development affects postnatal T. Mouse embryos were cultured from pronuclear to blastocyst stage in either standard (37 °C) or high (38 °C) temperature, and the T of each grown-up adult was measured.

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Article Synopsis
  • - The study investigates how calcium (Ca) transfer between the endoplasmic reticulum (ER) and mitochondria, crucial for energy production, is affected by the distance between these organelles, particularly in the context of Parkinson's disease (PD).
  • - Researchers found that a specific distance of approximately 20 nm between ER and mitochondria enhances Ca transfer and supports optimal mitochondrial function, highlighting the importance of maintaining this distance.
  • - In astrocytes derived from PD patients, the natural distance for efficient Ca transfer was reduced, leading to decreased mitochondrial function, but restoring the 20 nm distance improved Ca uptake, suggesting new ways to manage mitochondrial health.
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The extent to which calcium signaling participates in specific events of animal cell meiosis or mitosis is a subject of enduring controversy. We have previously demonstrated that buffering intracellular calcium with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA, a fast calcium chelator), but not ethylenebis(oxyethylenenitrilo)tetraacetic acid (EGTA, a slow calcium chelator), rapidly depolymerizes spindle microtubules in oocytes, suggesting that spindle assembly and/or stability requires calcium nanodomains-calcium transients at extremely restricted spatial-temporal scales. In this study, we have investigated the function of inositol-1,4,5-trisphosphate receptor (IPR), an endoplasmic reticulum (ER) calcium channel, in spindle assembly using Trim21-mediated depletion of IPR.

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"Neurochemistry" in Japan was established by intensive cooperation between psychiatrists and their collaborators, biochemists, who have sought to investigate the etiology of mental illness to establish treatments. It was a completely different direction from the flow of modern biochemistry that was born using microorganisms or eukaryotic cells as research materials. Neurochemists aimed to elucidate the physiological or pathological functions of the brain through chemical analysis of the morphologically and functionally unique complexity and characteristics of brain.

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In hippocampal CA1 neurons of wild-type mice, a short tetanus (15 or 20 pulses at 100 Hz) or a standard tetanus (100 pulses at 100 Hz) to a naive input pathway induces long-term potentiation (LTP) of the responses. Low-frequency stimulation (LFS; 1000 pulses at 1 Hz) 60 min after the standard tetanus reverses LTP (depotentiation [DP]), while LFS applied 60 min prior to the standard tetanus suppresses LTP induction (LTP suppression). We investigated LTP, DP, and LTP suppression of both field excitatory postsynaptic potentials and population spikes in CA1 neurons of mice lacking the inositol 1,4,5-trisphosphate (IP) receptor (IPR)-binding protein released with IP (IRBIT).

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Hyperactive Notch signalling is frequently observed in breast cancer and correlates with poor prognosis. However, relatively few mutations in the core Notch signalling pathway have been identified in breast cancer, suggesting that as yet unknown mechanisms increase Notch activity. Here we show that increased expression levels of GIT1 correlate with high relapse-free survival in oestrogen receptor-negative (ER(-)) breast cancer patients and that GIT1 mediates negative regulation of Notch.

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Pyruvate kinase isoform M2 (PKM2) is a rate-limiting glycolytic enzyme that is widely expressed in embryonic tissues. The expression of PKM2 declines in some tissues following embryogenesis, while other pyruvate kinase isozymes are upregulated. However, PKM2 is highly expressed in cancer cells and is believed to play a role in supporting anabolic processes during tumour formation.

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Calcium signaling is essential for regulating many biological processes. Endoplasmic reticulum inositol trisphosphate receptors (IPRs) and the mitochondrial Ca uniporter (MCU) are key proteins that regulate intracellular Ca concentration. Mitochondrial Ca accumulation activates Ca-sensitive dehydrogenases of the tricarboxylic acid (TCA) cycle that maintain the biosynthetic and bioenergetic needs of both normal and cancer cells.

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Anti-apoptotic Bcl-2-family members not only act at mitochondria but also at the endoplasmic reticulum, where they impact Ca dynamics by controlling IP receptor (IPR) function. Current models propose distinct roles for Bcl-2 vs. Bcl-xL, with Bcl-2 inhibiting IPRs and preventing pro-apoptotic Ca release and Bcl-xL sensitizing IPRs to low [IP] and promoting pro-survival Ca oscillations.

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Ten-eleven translocation (TET) proteins, the dioxygenase for DNA hydroxymethylation, are important players in nervous system development and diseases. However, their role in myelination and remyelination after injury remains elusive. Here, we identify a genome-wide and locus-specific DNA hydroxymethylation landscape shift during differentiation of oligodendrocyte-progenitor cells (OPC).

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Astrocytes are sensitive to ongoing neuronal/network activities and, accordingly, regulate neuronal functions (synaptic transmission, synaptic plasticity, behavior, etc.) by the context-dependent release of several gliotransmitters (e.g.

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Derlin family members (Derlins) are primarily known as components of the endoplasmic reticulum-associated degradation pathway that eliminates misfolded proteins. Here we report a function of Derlins in the brain development. Deletion of or in the central nervous system of mice impaired postnatal brain development, particularly of the cerebellum and striatum, and induced motor control deficits.

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Extensive activation of glial cells during a latent period has been well documented in various animal models of epilepsy. However, it remains unclear whether activated glial cells contribute to epileptogenesis, i.e.

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Anion exchanger 2 (AE2) plays crucial roles in regulating cell volume homeostasis and cell migration. We found that both IRBIT and Long-IRBIT (L-IRBIT) interact with anion exchanger 2 (AE2). The interaction occurred between the conserved AHCY-homologous domain of IRBIT/L-IRBIT and the N-terminal cytoplasmic region of AE2.

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Astrocytes are critical regulators of CNS function and are proposed to be heterogeneous in the developing brain and spinal cord. Here we identify a population of astrocytes located in the superficial laminae of the spinal dorsal horn (SDH) in adults that is genetically defined by Hes5. In vivo imaging revealed that noxious stimulation by intraplantar capsaicin injection activated Hes5 SDH astrocytes via α-adrenoceptors (α-ARs) through descending noradrenergic signaling from the locus coeruleus.

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Background: Chronic itch is a debilitating symptom of inflammatory skin diseases, but the underlying mechanism is poorly understood. We have recently demonstrated that astrocytes in the spinal dorsal horn become reactive in models of atopic and contact dermatitis via activation of the transcription factor signal transducer and activator of transcription 3 (STAT3) and critically contribute to chronic itch. In general, STAT3 is transiently activated; however, STAT3 activation in reactive astrocytes of chronic itch model mice persistently occurs via an unknown mechanism.

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Key Points: Neuronal activity causes astrocytic volume change via K uptake through TREK-1 containing two-pore domain potassium channels. The volume transient is terminated by Cl efflux through the Ca -activated anion channel BEST1. The source of the Ca required to open BEST1 appears to be the stretch-activated TRPA1 channel.

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The GABAergic synapses, a primary inhibitory synapse in the mammalian brain, is important for the normal development of brain circuits, and for the regulation of the excitation-inhibition balance critical for brain function from the developmental stage throughout life. However, the molecular mechanism underlying the formation, maintenance, and modulation of GABAergic synapses is less understood compared to that of excitatory synapses. Quantum dot-single particle tracking (QD-SPT), a super-resolution imaging technique that enables the analysis of membrane molecule dynamics at single-molecule resolution, is a powerful tool to analyze the behavior of proteins and lipids on the plasma membrane.

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Astrocytic Ca signals can be fast and local, supporting the idea that astrocytes have the ability to regulate single synapses. However, the anatomical basis of such specific signaling remains unclear, owing to difficulties in resolving the spongiform domain of astrocytes where most tripartite synapses are located. Using 3D-STED microscopy in living organotypic brain slices, we imaged the spongiform domain of astrocytes and observed a reticular meshwork of nodes and shafts that often formed loop-like structures.

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Mucociliary clearance through coordinated ciliary beating is a major innate defense removing pathogens from the lower airways, but the pathogen sensing and downstream signaling mechanisms remain unclear. We identified virulence-associated formylated bacterial peptides that potently stimulated ciliary-driven transport in the mouse trachea. This innate response was independent of formyl peptide and taste receptors but depended on key taste transduction genes.

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During neurodevelopment, the growth cone deciphers directional information from extracellular guidance cues presented as shallow concentration gradients via signal amplification. However, it remains unclear how the growth cone controls this amplification process during its navigation through an environment in which basal cue concentrations vary widely. Here, we identified inositol 1,4,5-trisphosphate (IP) receptor type 3 as a regulator of axonal sensitivity to guidance cues in vitro and in vivo.

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Being the largest the Ca store in mammalian cells, endoplasmic reticulum (ER)-mediated Ca signalling often involves both Ca release via inositol 1, 4, 5-trisphosphate receptors (IPR) and store operated Ca entries (SOCE) through Ca release activated Ca (CRAC) channels on plasma membrane (PM). IPRs are functionally coupled with CRAC channels and other Ca handling proteins. However, it still remains less well defined as to whether IPRs could regulate ER-mediated Ca signals independent of their Ca releasing ability.

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