A5015389182- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Receptor Mechanisms and Signaling
- Neurogenesis and neuroplasticity mechanisms
- Photoreceptor and optogenetics research
- Cellular transport and secretion
- Amino Acid Enzymes and Metabolism
- Hearing, Cochlea, Tinnitus, Genetics
- Neuroinflammation and Neurodegeneration Mechanisms
- Retinal Development and Disorders
- RNA regulation and disease
- Nerve injury and regeneration
- Advanced Fluorescence Microscopy Techniques
- Chemical Synthesis and Analysis
- Vestibular and auditory disorders
- Lipid Membrane Structure and Behavior
- Molecular Sensors and Ion Detection
- Photochromic and Fluorescence Chemistry
- Memory and Neural Mechanisms
- Mitochondrial Function and Pathology
- Click Chemistry and Applications
- Congenital heart defects research
- Neuroscience and Neural Engineering
- Autophagy in Disease and Therapy
- Axon Guidance and Neuronal Signaling
Keio University
2015-2024
Japan Science and Technology Agency
2001-2024
Keio University Hospital
2004-2018
Howard Hughes Medical Institute
2013
Boston Children's Hospital
2013
Massachusetts General Hospital
2013
University of California, San Francisco
2013
Science and Technology Corporation (United States)
2013
Centre de Recherche en Économie et Statistique
2013
Centre for Research in Engineering Surface Technology
2013
Cbln1, secreted from cerebellar granule cells, and the orphan glutamate receptor delta2 (GluD2), expressed by Purkinje are essential for synapse integrity between these neurons in adult mice. Nevertheless, no endogenous binding partners molecules have been identified. We found that Cbln1 binds directly to N-terminal domain of GluD2. GluD2 expression postsynaptic combined with exogenously applied was necessary sufficient induce new synapses vitro cerebellum vivo. Further, beads coated...
Neurotransmitter receptors are essential components of synapses for communication between neurons in the brain. Because spatiotemporal expression profiles and dynamics neurotransmitter involved many functions delicately governed brain, vivo research tools with high resolution intact brains highly desirable. Covalent labeling by chemical reaction (chemical labeling) proteins without genetic manipulation is now a powerful method analyzing vitro. However, selective target receptor brain has not...
Glial cells express a variety of neurotransmitter receptors. Notably, Bergmann glial in the cerebellum have Ca2+-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPARs) assembled without GluR2 subunit. To elucidate role these AMPARs, we converted them into Ca2+-impermeable by adenoviral-mediated delivery gene. This conversion retracted processes ensheathing synapses on Purkinje cell dendritic spines and retarded removal synaptically...
Ca 2+ -dependent activator protein for secretion 2 (CAPS2/CADPS2) is a secretory granule-associated that abundant at the parallel fiber terminals of granule cells in mouse cerebellum and involved release neurotrophin-3 (NT-3) brain-derived neurotrophic factor (BDNF), both which are required cerebellar development. The human homolog gene on chromosome 7 located within susceptibility locus 1 autism, disease characterized by several morphological abnormalities. Here we report CAPS2 knock-out...
Transmitting signals across the synapse Glutamate receptors located on neuronal cells play a role in mediating electrical at excitatory synapses. These glutamatergic synapses are extremely important for nearly all cognitive functions. Elegheert et al. analyzed complex that bridges synapse, comprising β-neurexin 1, cell adhesion molecule surface of presynaptic axons; cerebellin synaptic organizer; and postsynaptic glutamate receptor GluD2. The structural functional analysis provides insight...
Abstract The location and number of neurotransmitter receptors are dynamically regulated at postsynaptic sites. However, currently available methods for visualizing receptor trafficking require the introduction genetically engineered into neurons, which can disrupt normal functioning processing original receptor. Here we report a powerful method native α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate (AMPARs) essential cognitive functions without any genetic...
Synthetic excitatory synaptic organizer The human brain contains trillions of synapses within a vast network neurons. Synapse remodeling is essential to ensure the efficient reception and integration external stimuli store retrieve information. Building occurs throughout life under control proteins. Errors in this process can lead neuropsychiatric or neurological disorders. Suzuki et al. combined structural elements natural organizers develop an artificial version called CPTX, which has...
To identify the genetic cause of a syndrome causing cerebellar ataxia and eye movement abnormalities.We identified 2 families with ataxia, abnormalities, global developmental delay. We performed analyses including single nucleotide polymorphism genotyping, linkage analysis, array comparative genomic hybridization, quantitative PCR, Sanger sequencing. obtained recordings mutant mice deficient for ortholog candidate gene, immunohistochemistry using human mouse brain specimens.All affected...
Significance Long-term depression (LTD) commonly affects learning and memory in various brain regions. Although LTD the cerebellum absolutely requires δ2 glutamate receptors, its underlying mechanisms remain elusive. is caused by endocytosis of AMPA which triggered activity-induced serine phosphorylation GluA2 subunit. Our work showed that this required prior dephosphorylation nearby tyrosine residue. By interaction with a phosphatase, receptors regulated status to gate inducibility LTD....
Long-term potentiation (LTP) is mediated by the activity-driven delivery of GluR1 glutamate receptors via Ca 2+ /calmodulin-dependent protein kinase II activity in various brain regions. Recently, postsynaptic LTP was shown to be induced at parallel fiber-Purkinje cell synapses stimulating fibers 1 Hz or applying a NO donor. Here, we demonstrate that NO-evoked mice cerebellum blocked botulinum toxin and enhanced prior treatment with phorbol ester, which known induce GluR2 endocytosis....
The δ2 glutamate receptor (GluRδ2) is predominantly expressed in Purkinje cells and plays crucial roles cerebellar functions: GluR δ 2 −/− mice display ataxia impaired motor learning. In addition, long-term depression (LTD) at parallel fiber (PF)–Purkinje cell synapses abrogated, synapse formation with PFs climbing fibers (CFs) severely disturbed cells. Recently, we demonstrated that abrogated LTD was restored by the virus-mediated expression of wild-type transgene ( Tg wt ) but not mutant...
Myoblast fusion is tightly regulated during development and regeneration of muscle fibers. BAI3 a receptor that orchestrates myoblast via Elmo/Dock1 signaling, but the mechanisms regulating its activity remain elusive. Here we report mice lacking display small fibers inefficient after cardiotoxin-induced injury. We describe two proteins repress or activate in progenitors. find secreted C1q-like1-4 by specifically interacting with BAI3. Using proteomic approach, identify Stabilin-2 as protein...
Mutations in the gene encoding chromatin remodeler chromodomain helicase DNA-binding protein 8 (CHD8) are a highly penetrant risk factor for autism spectrum disorder (ASD). Although cerebellar abnormalities have long been thought to be related ASD pathogenesis, it has remained largely unknown whether dysfunction of CHD8 cerebellum contributes phenotypes. We here show that granule neuron progenitor (GNP)-specific deletion Chd8 mice impairs proliferation and differentiation these cells as well...
Abstract In the central nervous system, astrocytes enable appropriate synapse function through glutamate clearance from synaptic cleft; however, it remains unclear how astrocytic transporters at peri-synaptic contact. Here, we report that Down syndrome cell adhesion molecule (DSCAM) in Purkinje cells controls formation and developing cerebellum. Dscam -mutant mice show defects CF translocation as is observed loss of mutations transporter GLAST expressed Bergmann glia. These impaired...
Glutamate transporters are essential for terminating excitatory neurotransmission. Two distinct glutamate transporters, glutamate–aspartate transporter (GLAST) and amino acid 4 (EAAT4), expressed most abundantly in the molecular layer of cerebellar cortex. GLAST is Bergmann glial processes surrounding synapses on Purkinje cell dendritic spines, whereas EAAT4 concentrated extrasynaptic regions spine membranes. To clarify functional significance coexistence these we analyzed kinetics EPSCs...
The δ2 glutamate receptor (GluRδ2; GluD2), which is predominantly expressed on postsynaptic sites at parallel fiber (PF)–Purkinje cell synapses in the cerebellum, plays two crucial roles cerebellum: formation of PF and regulation long-term depression (LTD), a form synaptic plasticity underlying motor learning. Although induction LTD learning absolutely require signaling via cytoplasmic C-terminal domain GluD2, mechanisms by GluD2 regulates synaptogenesis have remained unclear. Here, we...
Key points NMDA receptors (NMDARs) are required for long‐term depression (LTD) at parallel fibre–Purkinje cell synapses, but their cellular localization and physiological functions in vivo unclear. NMDARs molecular‐layer interneurons (MLIs), not granule cells or Purkinje cells, LTD, potentiation induced by low‐frequency stimulation of fibres. Nitric oxide produced NMDAR activation MLIs probably mediates LTD induction. dispensable motor learning during adaptation horizontal optokinetic...