A5027742984- Neurogenesis and neuroplasticity mechanisms
- Cellular transport and secretion
- Nerve injury and regeneration
- RNA regulation and disease
- Signaling Pathways in Disease
- RNA Research and Splicing
- Protein Kinase Regulation and GTPase Signaling
- Axon Guidance and Neuronal Signaling
- Receptor Mechanisms and Signaling
- Endoplasmic Reticulum Stress and Disease
- Hereditary Neurological Disorders
- Cellular Mechanics and Interactions
- interferon and immune responses
- Pluripotent Stem Cells Research
- Microtubule and mitosis dynamics
- Melanoma and MAPK Pathways
- Neuroendocrine regulation and behavior
- MicroRNA in disease regulation
- Genetics and Neurodevelopmental Disorders
- Pancreatic function and diabetes
- Neuroscience and Neuropharmacology Research
- Heat shock proteins research
- Circadian rhythm and melatonin
- RNA Interference and Gene Delivery
- Cell Adhesion Molecules Research
National Center For Child Health and Development
2016-2025
Tokyo Metropolitan Institute of Medical Science
2022-2025
Tokyo University of Pharmacy and Life Sciences
2017-2025
RIKEN Center for Biosystems Dynamics Research
2024
Tokyo Medical and Dental University
2013-2016
Nara Medical University
2016
Kitasato University
2012-2013
Tokyo Institute of Technology
1997-2012
Japan Health Sciences Foundation
2012
Pharmac
2010-2011
Neurotrophins are recognized widely as essential factors in the developing nervous system. Previously, we demonstrated that neurotrophin 3 activation of TrkC inhibits Schwann cell myelination and enhances migration primary cells through signaling pathway regulated by Rho GTPases Rac1 Cdc42. Here, show neurotrophins activate divergent pathways to promote or inhibit migration. Endogenous brain-derived neurotrophic factor acting p75 NTR dramatically Src kinase-dependent guanine-nucleotide...
Various extracellular stimuli activate three classes of mitogen-activated protein kinases (MAPKs): signal-regulated kinase, c-Jun N-terminal and p38 MAPK. In mammalian cells, MAPK is activated by endotoxins, inflammatory cytokines, environmental stresses. We show here that also upon stimulation G protein-coupled receptors (Gq/G11-coupled m1 Gi-coupled m2 muscarinic acetylcholine Gs-coupled β-adrenergic receptors) in human embryonal kidney 293 cells. The activation through the was completely...
Cell polarity is critical in various cellular processes ranging from cell migration to asymmetric division and axon dendrite specification. Similarly, myelination by Schwann cells polarized, but the mechanisms involved remain unclear. Here, we show that protein Par-3 localizes asymmetrically at axon-glial junction disruption of localization, overexpression knockdown, inhibits myelination. Additionally, directly associates recruits p75 neurotrophin receptor junction, forming a complex...
During development and nerve injury, complex interactions between glial cells neurons are essential for establishing proper function. Neurotrophins play multiple roles in the developing nervous system, including cell survival, growth, differentiation. Here we show that migration of Schwann cells, isolated from sciatic nerves, is significantly enhanced by neurotrophin 3, but not growth factor or brain-derived neurotrophic factor. The neurotrophin-3-induced was also observed nerves p75NTR-/-...
Small GTPases of the Rho family play key roles in formation neuronal axons and dendrites by transducing signals from guidance cues, such as neurotrophins, to actin cytoskeleton. However, there is little insight into mechanism which neurotrophins regulate GTPases. Here, we show crucial role ubiquitous Rac1-specific guanine nucleotide exchange factor, Tiam1 (T lymphoma invasion metastasis 1), a neurotrophin-mediated change cell shape. We demonstrate that BDNF, acting through TrkB, directly...
The cellular events that precede myelination in the peripheral nervous system require rapid and dynamic morphological changes Schwann cell. These are thought to be mainly controlled by axonal signals. But how signals on axons coordinately organized transduced promote proliferation, migration, radial sorting, is unknown. We describe signal neuregulin-1 (NRG1) controls cell migration via activation of atypical Dock180-related guanine nucleotide exchange factor (GEF) Dock7 subsequent Rho...
Myelin formation of the CNS is a complex and dynamic process. Before onset myelination, oligodendrocytes (OLs), myelin-forming glia CNS, proliferate migrate along axons. Little known about molecular mechanisms underlying early myelination processes. Here, we show that platelet-derived growth factor (PDGF), crucial physiological ligand in OL development, controls migration oligodendrocyte precursor cells (OPCs) through cyclin-dependent kinase 5 (Cdk5). PDGF stimulates Cdk5 activity...
Arginine-vasopressin (AVP) is known to be involved in maintaining glucose homeostasis, and AVP-resistance observed poorly controlled non-insulin-dependent diabetes mellitus subjects, resulting a lowered plasma volume. Recently we reported that V1a vasopressin receptor-deficient (V1aR(-/-)) mice exhibited decreased circulating blood volume hypermetabolism of fat accompanied with impaired insulin-signaling. Here further investigated the roles AVP/V1a receptor regulating homeostasis using...
Background An arg120gly (R120G) missense mutation in HSPB5 (α-β-crystallin ), which belongs to the small heat shock protein (HSP) family, causes desmin-related cardiomyopathy (DRM), a muscle disease that is characterized by formation of inclusion bodies, can contain pre-amyloid oligomer intermediates (amyloid oligomer). While we have shown HSPs directly interrupt amyloid formation, vivo protective effects on development DRM still uncertain. Methodology/Principal Findings In order extend...
Cholangiocarcinoma (CCA) is a cancer arising from the neoplastic transformation of cholangiocytes. During tumorigenesis, tumor suppressor and cancer-related genes are commonly silenced by aberrant DNA methylation in their promoter regions. Zebularine (1-(β-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one) acts as an inhibitor exhibits chemical stability minimal cytotoxicity both vitro vivo. In this study, we explore effect possible mechanism action zebularine on CCA cells. We demonstrate that...
Mitogen-activated protein kinases (MAPKs) are activated by various extracellular stimuli. The signaling pathways from G protein-coupled receptors to signal-regulated kinase have been partially elucidated, whereas the mechanisms which stimulate c-Jun N-terminal (JNK) and p38 MAPK activities remain largely unknown. We recently demonstrated that signal Gq/11-coupled m1 muscarinic acetylcholine receptor is mediated both Gαq/11 Gβγ in HEK-293 cells (Yamauchi, J., Nagao, M., Kaziro, Y., Itoh, H....
Endogenous neurotrophins positively and negatively regulate migration of premyelinating Schwann cells before the initiation myelination. Neurotrophin-3 (NT3) acting through TrkC receptor tyrosine kinase stimulates cell via Rho GTPases Rac1 Cdc42. We previously demonstrated that directly phosphorylates activates Dbs, guanine-nucleotide exchange factor (GEF) for Cdc42, to partially mediate migration. Here, we identify T lymphoma invasion metastasis (Tiam) 1 as Rac1-specific involved in...
Oligodendrocyte precursor cells (OPCs) differentiate into oligodendrocytes (OLs) in order to form myelin, which is required for the rapid propagation of action potentials vertebrate nervous system. In spite considerable clinical importance myelination, little known about basic molecular mechanisms underlying OL differentiation and myelination. Here, we show that cyclin-dependent kinase (Cdk) 5 activated following induction differentiation, Cdk5 inhibitor roscovitine inhibits differentiation....
The neuropeptide hormone arginine-vasopressin (AVP) is well known to exert its antidiuretic effect via the vasopressin V2 receptor (V2R), whereas role of V1a (V1aR) in kidney remains be clarified. Previously, we reported decreased plasma volume and blood pressure receptor-deficient (V1aR-/-) mice (Koshimizu T, Nasa Y, Tanoue A, Oikawa R, Kawahara Kiyono Adachi Tanaka Kuwaki Mori T. Proc Natl Acad Sci USA 103: 7807-7812, 2006). In this study, investigated V1aR urine concentration, renal...
The phosphorylation status of Dock6 causes sensory neuron axons to switch from extension branching.
Alpha(1)-adrenoceptor antagonists are extensively used in the treatment of hypertension and lower urinary tract symptoms associated with benign prostatic hyperplasia. Among side effects, ejaculatory dysfunction occurs more frequently drugs that relatively selective for alpha(1A)-adrenoceptors compared other this class. This suggests may contribute to ejaculation. However, has not been studied at molecular level.The physiological contribution each alpha(1)-adrenoceptor subtype was...
We have reported that [Arg(8)]-vasopressin-stimulated insulin release is blunted in islet cells isolated from V1b receptor-deficient (V1bR(-/-)) mice. In this study, we used V1bR(-/-) mice to examine the physiological role of receptor regulating blood glucose levels vivo, and found fasting plasma glucose, glucagon were lower than wild-type (V1bR(+/+)) Next, evaluated tolerance by performing an intraperitoneal test (GTT). The during GTT V1bR(+/+) An (ITT) revealed that, after administration,...
The formation of primitive adipose tissue is the initial process in development followed by migration preadipocytes into adipocyte clusters. Comparatively little known about molecular mechanism controlling preadipocyte migration. Here, we show that cytohesin-2, guanine-nucleotide exchange factor for Arf family GTP-binding proteins, regulates mouse 3T3-L1 cells through Arf6. SecinH3, a specific inhibitor cytohesin family, markedly inhibits cells. express cytohesin-2 and cytohesin-3, knockdown...
Transgenic and knockout mice reveal a pathway that controls the extent of myelination by Schwann cells.
Hepatocellular carcinoma is one of the most common cancers worldwide. During tumorigenesis, tumor suppressor and cancer-related genes are commonly silenced by aberrant DNA methylation in their promoter regions. Zebularine (1-(β-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one) acts as an inhibitor exhibits chemical stability minimal cytotoxicity both vitro vivo. In this study, we explore effect possible mechanism action zebularine on hepatocellular cell line HepG2. We demonstrate that antitumor...