A5026117179- Ion channel regulation and function
- Amyotrophic Lateral Sclerosis Research
- Cellular transport and secretion
- Neuroscience and Neuropharmacology Research
- Neurogenetic and Muscular Disorders Research
- Muscle Physiology and Disorders
- Nerve injury and regeneration
- Neuroscience and Neural Engineering
- Neurobiology and Insect Physiology Research
- Neurogenesis and neuroplasticity mechanisms
- Myasthenia Gravis and Thymoma
- Cell Adhesion Molecules Research
- Genetic Neurodegenerative Diseases
- Parkinson's Disease Mechanisms and Treatments
- Mitochondrial Function and Pathology
- Lipid Membrane Structure and Behavior
- Axon Guidance and Neuronal Signaling
- Coenzyme Q10 studies and effects
- Muscle activation and electromyography studies
- Connexins and lens biology
- Adipose Tissue and Metabolism
- Signaling Pathways in Disease
- Neural Networks and Applications
- Autophagy in Disease and Therapy
- Biochemical and Structural Characterization
Tokyo Metropolitan Institute of Gerontology
2020-2025
University of Kansas Medical Center
2009-2024
Tokyo University of Agriculture and Technology
2022-2024
Institute of Neurobiology
2024
University of Kansas
2010-2021
The Ohio State University Wexner Medical Center
2018
Harvard University
2004-2010
The University of Kansas Health System
2009
Institut de Biologie Moléculaire et Cellulaire
2008
Institute of Cell Biology and Neurobiology
2008
Amyotrophic lateral sclerosis (ALS) is a synaptopathy accompanied by the presence of cytoplasmic aggregates containing TDP-43, an RNA-binding protein linked to ∼97% ALS cases. Using Drosophila model ALS, we show that TDP-43 overexpression (OE) in motor neurons results decreased expression Hsc70-4 chaperone at neuromuscular junction (NMJ). Mechanistically, mutant sequesters hsc70-4 mRNA and impairs its translation. Expression ortholog, HSPA8, also reduced primary NMJs mice expressing TDP-43....
A prominent feature of synaptic maturation at the neuromuscular junction (NMJ) is topological transformation acetylcholine receptor (AChR)-rich postsynaptic membrane from an ovoid plaque into a complex array branches. We show here that laminins play autocrine role in promoting this transformation. Laminins containing α4, α5, and β2 subunits are synthesized by muscle fibers concentrated small portion basal lamina passes through cleft NMJ. Topological AChR clusters was delayed targeted mutant...
Mammalian limb and trunk skeletal muscles are composed of muscle fibers that differ in contractile molecular properties. They commonly divided into four categories according to the myosin heavy chain they express: I, IIA, IIX IIB, ranging from slowest fastest. Individual motor axons innervate tens fibers, nearly all which same type. The mechanisms accounting for this striking specificity, termed unit homogeneity, remain incompletely understood, part because there have been no markers...
Synapse formation requires the organization of presynaptic active zones, synaptic vesicle release sites, in precise apposition to postsynaptic neurotransmitter receptor clusters; however, molecular mechanisms responsible for these processes remain unclear. Here, we show that P/Q-type and N-type voltage-dependent calcium channels (VDCCs) play essential roles as scaffolding proteins zones. The neuromuscular junction double knock-out mice P/Q- VDCCs displayed a normal size but had significantly...
Abstract Presynaptic active zones play a pivotal role as synaptic vesicle release sites for transmission, but the molecular architecture of in mammalian neuromuscular junctions (NMJs) at sub-diffraction limited resolution remains unknown. Bassoon and Piccolo are zone specific cytosolic proteins essential assembly NMJs, ribbon synapses brain synapses. These thought to colocalize share some functions zones. Here, we report an unexpected finding non-overlapping localization these two mouse NMJs...
Presynaptic active zones are essential structures for synaptic vesicle release, but the developmental regulation of their number and maintenance during aging at mammalian neuromuscular junctions (NMJs) remains unknown. Here, we analyzed distribution in developing, mature, aged mouse NMJs by immunohistochemical detection zone-specific protein Bassoon. Bassoon is a cytosolic scaffolding zone assembly ribbon synapses some brain synapses. staining showed punctate pattern nerve terminals axons...
Motor neurons in amyotrophic lateral sclerosis (ALS) patients and animal models show degeneration from the nerve terminal, known as dying-back neuropathy. To investigate mechanism underlying this neuropathy, we analyzed neuromuscular junctions (NMJs) motor neuron cell bodies SOD1G93A mice using electron microscopy. NMJs of exhibited significantly higher numbers autophagosomes degenerated mitochondria compared to wild-type controls. Mitophagosomes were identified NMJ presynaptic terminals...
The P/Q-type voltage-dependent calcium channels (VDCCs) are essential for synaptic transmission at adult mammalian neuromuscular junctions (NMJs); however, the subsynaptic location of VDCCs relative to active zones in rodent NMJs, and functional modification by interaction with zone protein Bassoon remain unknown. Here, we show that distribute a punctate pattern within NMJ presynaptic terminals align three dimensions Bassoon. This distribution NMJs is consistent our previous study...
Human parvovirus B19 (B19V) infection of human erythroid progenitor cells (EPCs) induces a DNA damage response and cell cycle arrest at late S phase, which facilitates viral replication. However, it is not clear exactly cellular factors are employed by this single-stranded virus. Here, we used microarrays to systematically analyze the dynamic transcriptome EPCs infected with B19V. We found that metabolism, replication, repair, response, cycle, pathways were significantly regulated after B19V...
Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease characterized by specific loss of motor neurons in the spinal cord and brain stem. Although ALS has historically been as neuron disease, there evidence that degenerate retrograde manner, beginning periphery at junctions (NMJs) skeletal muscle. We recently reported vesicle trafficking protein Bet1L (Bet1 Golgi Vesicular Membrane Trafficking Protein Like) new molecule possibly linked to NMJ degeneration ALS. In this study, we...
Neural circuits transmit information through synapses, and the efficiency of synaptic transmission is closely related to density presynaptic active zones, where vesicles are released. The goal this review highlight recent insights into molecular mechanisms that control number zones per terminal (active zone density) during developmental stimulus-dependent changes in efficacy. At neuromuscular junctions (NMJs), preserved across species, remains constant development, same between synapses with...
Since the first report of experimental animal models myasthenia gravis (MG) with autoantibodies against low-density lipoprotein receptor-related protein 4 (LRP4), there have not been any major reports replicating pathogenicity anti-LRP4 antibodies (Abs). Recent clinical studies cast doubt on specificity and for MG, highlighting need further research. In this study, we purified antigens corresponding to extracellular region human LRP4 stably expressed chaperones in 293 cells used these...
Abstract Many neurotrophic factors with survival activity for motoneurons in vivo were first identified using cultures of purified embryonic motoneurons. The L1 neural cell adhesion molecule has multiple roles brain development. We showed by situ hybridization and RT‐PCR that mRNA was expressed at significant levels postnatal spinal cord. therefore cultured from E14 rat embryos the absence trophic but L1‐Fc CHL1‐Fc fusion proteins. prevented death approximately half saved BDNF a...
Axons and dendrites of developing neurons establish distributed innervation patterns enabling precise discrimination in sensory systems. We describe the role extracellular matrix molecule, laminin β2, interacting with Ca V 2.2 calcium channel establishing appropriate innervation. In vivo , is expressed on growth cones Xenopus laevis neurites β2 skin. Culturing a substrate inhibits neurite outgrowth specific calcium-dependent manner. Blocking signaling between leads to increased numbers...