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https://www.readbyqxmd.com/read/28213447/the-drosophila-postsynaptic-deg-enac-channel-ppk29-contributes-to-excitatory-neurotransmission
#1
Alexis Hill, Xingguo Zheng, Xiling Li, Ross McKinney, Dion Dickman, Yehuda Ben-Shahar
The protein family of Degenerin/Epithelial Sodium Channels (DEG/ENaC) is comprised of diverse animal-specific, non-voltage-gated ion channels that play important roles in regulating cationic gradients across epithelial barriers. Some family members are also enriched in neural tissues in both vertebrates and invertebrates. However, the specific neurophysiological functions of most DEG/ENaC-encoding genes remain poorly understood. The fruit fly Drosophila melanogaster is an excellent model for deciphering the functions of DEG/ENaC genes because its genome encodes an exceptionally large number of DEG/ENaC subunits termed pickpocket (ppk) 1-31 Here we demonstrate that ppk29 contributes specifically to the postsynaptic modulation of excitatory synaptic transmission at the larval neuromuscular junction (NMJ)...
February 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28213440/muscle-yap-is-a-regulator-of-neuromuscular-junction-formation-and-regeneration
#2
Kai Zhao, Chengyong Shen, Yisheng Lu, Zhihui Huang, Lei Li, Christopher D Rand, Jinxiu Pan, Xiang-Dong Sun, Zhibing Tan, Hongsheng Wang, Guanglin Xing, Yu Cao, Guoqing Hu, Jiliang Zhou, Wen-Cheng Xiong, Lin Mei
Yes-associated protein (Yap) is a major effector of the Hippo pathway that regulates cell proliferation and differentiation during development and restricts tissue growth in adult animals. However, its role in synapse formation remains poorly understood. In this study, we characterized Yap's role in the formation of neuromuscular junction (NMJ). In HSA-Yap(-/-) mice where Yap was mutated specifically in muscle cells, AChR clusters were smaller and were distributed in a broader region in the middle of muscle fibers, suggesting that muscle Yap is necessary for the size and location of AChR clusters...
February 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28199191/trans-synaptic-homeostasis-at-the-myasthenic-neuromuscular-junction
#3
Jaap J Plomp
Properly sustained impulse transmission at the neuromuscular junction (NMJ) is crucial for successful muscle contraction. To guarantee this, NMJs not only possess a considerable safety factor in transmission but also have the ability to adjust the presynaptic acetylcholine release level to cope with any changes in the postsynaptic neurotransmitter sensitivity. This review will provide overview on the discovery and characterization of this synaptic homeostatic mechanism, especially in the condition of the neuromuscular disorder myasthenia gravis (MG) where the postsynaptic transmitter sensitivity at the NMJ becomes severely reduced due to autoimmune attack of acetylcholine receptors...
March 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28177226/large-area-ensemble-molecular-electronics-motivation-and-challenges
#4
Ayelet Vilan, Dinesh Aswal, David Cahen
We review charge transport across molecular monolayers, which is central to molecular electronics (MolEl), using large-area junctions (NmJ). We strive to provide a wide conceptual overview of three main subtopics. First, a broad introduction places NmJ in perspective to related fields of research and to single-molecule junctions (1mJ) in addition to a brief historical account. As charge transport presents an ultrasensitive probe for the electronic perfection of interfaces, in the second part ways to form both the monolayer and the contacts are described to construct reliable, defect-free interfaces...
February 8, 2017: Chemical Reviews
https://www.readbyqxmd.com/read/28123080/cortactin-is-a-regulator-of-activity-dependent-synaptic-plasticity-controlled-by-wingless
#5
Daniel Alicea, Marizabeth Perez, Carolina Maldonado, Carihann Dominicci-Cotto, Bruno Marie
: Major signaling molecules initially characterized as key early developmental regulators are also essential for the plasticity of the nervous system. Recently the Wingless (Wg)/Wnt pathway has been shown to underlie the structural and electrophysiological changes during activity-dependent synaptic plasticity at the Drosophila neuromuscular junction. A challenge remains to understand how this signal mediates the cellular changes underlying this plasticity. Here, we focus on the actin regulator Cortactin, a major organizer of protrusion, membrane mobility and invasiveness, and define its new role in synaptic plasticity...
January 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28120411/electrical-stimulation-delays-reinnervation-in-denervated-rat-muscle
#6
Clara M Pinheiro-Dardis, Bruna T Erbereli, Davilene Gigo-Benato, Paula A T S Castro, Thiago L Russo
INTRODUCTION: It is not clear if electrical stimulation (ES) can affect muscle reinnervation. This study aimed to verify if ES affects neuromuscular recovery after nerve crush injury in rats. METHODS: Denervated muscles were electrically stimulated daily for 6 or 14 days. Neuromuscular performance and excitability, and muscle morphology were determined. Muscle trophism markers (atrogin-1, MuRF-1, and myoD), as well as neuromuscular junction (NMJ) organization (MuSK, Dok-7, nAChR, and N-CAM) were assessed...
January 24, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/28103314/expression-of-a-mutant-sema3a-protein-with-diminished-signalling-capacity-does-not-alter-als-related-motor-decline-or-confer-changes-in-nmj-plasticity-after-botoxa-induced-paralysis-of-male-gastrocnemic-muscle
#7
Elizabeth B Moloney, Barbara Hobo, Fred De Winter, Joost Verhaagen
Terminal Schwann cells (TSCs) are specialized cells that envelop the motor nerve terminal, and play a role in the maintenance and regeneration of neuromuscular junctions (NMJs). The chemorepulsive protein semaphorin 3A (SEMA3A) is selectively up-regulated in TSCs on fast-fatigable muscle fibers following experimental denervation of the muscle (BotoxA-induced paralysis or crush injury to the sciatic nerve) or in the motor neuron disease amyotrophic lateral sclerosis (ALS). Re-expression of SEMA3A in this subset of TSCs is thought to play a role in the selective plasticity of nerve terminals as observed in ALS and following BotoxA-induced paralysis...
2017: PloS One
https://www.readbyqxmd.com/read/28100668/correction-to-nmj-morph-reveals-principal-components-of-synaptic-morphology-influencing-structure-function-relationships-at-the-neuromuscular-junction
#8
Ross A Jones, Caitlan D Reich, Kosala N Dissanayake, Fanney Kristmundsdottir, Gordon S Findlater, Richard R Ribchester, Martin W Simmen, Thomas H Gillingwater
No abstract text is available yet for this article.
January 2017: Open Biology
https://www.readbyqxmd.com/read/28088107/gaas-laser-therapy-reestablishes-the-morphology-of-the-nmj-and-nachrs-after-injury-due-to-bupivacaine
#9
Cristiane Neves Alessi Pissulin, Paula Aiello Tomé de Souza Castro, Flávio Codina, Carina Guidi Pinto, Ivan Jose Vechetti-Junior, Selma Maria Michelin Matheus
BACKGROUND: Local anesthetics are used to relieve pre- and postoperative pain, acting on both sodium channels and nicotinic acetylcholine receptors (nAChR) at the neuromuscular junction (NMJ). Bupivacaine acts as a non-competitive antagonist and has limitations, such as myotoxicity, neurotoxicity, and inflammation. Low-level laser therapy (LLLT) has anti-inflammatory, regenerative, and analgesic effects. The aim of the present study was to evaluate the effects of a gallium arsenide laser (GaAs) on the morphology of the NMJ and nAChRs after application of bupivacaine in the sternomastoid muscle...
December 22, 2016: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28073926/mutations-of-pqbp1-in-renpenning-syndrome-promote-ubiquitin-mediated-degradation-of-fmrp-and-cause-synaptic-dysfunction
#10
Xiao-Yan Zhang, Junxia Qi, Yu-Qian Shen, Xian Liu, An Liu, Zikai Zhou, Junhai Han, Zi Chao Zhang
Renpenning syndrome is a group of X-linked intellectual disability (XLID) syndromes caused by mutations in human polyglutamine-binding protein 1 (PQBP1) gene. Little is known about the molecular pathogenesis of the various mutations that cause the notable variability in patients. In this study, we examine the cellular and synaptic functions of the most common mutations found in the patients: c.461_462delAG, c.459_462delAGAG, and c.463_464dupAG in an AG hexamer in PQBP1 exon 4. We discovered that PQBP1 c.459_462delAGAG and c...
January 10, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28072465/splicing-regulation-and-dysregulation-of-cholinergic-genes-expressed-at-the-neuromuscular-junction
#11
REVIEW
Kinji Ohno, Mohammad Alinoor Rahman, Mohammad Nazim, Farhana Nasrin, Yingni Lin, Jun-Ichi Takeda, Akio Masuda
We humans have evolved by acquiring diversity of alternative RNA metabolisms including alternative means of splicing and transcribing non-coding genes, and not by acquiring new coding genes. Tissue-specific and developmental stage-specific alternative RNA splicing is achieved by tightly regulated spatiotemporal regulation of expressions and activations of RNA-binding proteins that recognize their cognate splicing cis-elements on nascent RNA transcripts. Genes expressed at the neuromuscular junction (NMJ) are also alternatively spliced...
January 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28069867/the-carboxyl-terminal-region-of-dok-7-plays-a-key-but-not-essential-role-in-activation-of-muscle-specific-receptor-kinase-musk-and-neuromuscular-synapse-formation
#12
Ryo Ueta, Tohru Tezuka, Yosuke Izawa, Sadanori Miyoshi, Satoru Nagatoishi, Kouhei Tsumoto, Yuji Yamanashi
As the synapse between a motor neuron and skeletal muscle, the neuromuscular junction (NMJ) is required for muscle contraction. The formation and maintenance of NMJs are controlled by the muscle-specific receptor kinase MuSK. Dok-7 is the essential cytoplasmic activator of MuSK, and indeed mice lacking Dok-7 form no NMJs. Moreover, DOK7 gene mutations underlie DOK7 myasthenia, an NMJ synaptopathy. Previously, we failed to detect MuSK activation in myotubes by Dok-7 mutated in the N-terminal pleckstrin homology (PH) or phosphotyrosine binding (PTB) domain or that lacked the C-terminal region (Dok-7-ΔC)...
January 7, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28056033/fiji-macro-3d-art-veselect-3d-automated-reconstruction-tool-for-vesicle-structures-of-electron-tomograms
#13
Kristin Verena Kaltdorf, Katja Schulze, Frederik Helmprobst, Philip Kollmannsberger, Thomas Dandekar, Christian Stigloher
Automatic image reconstruction is critical to cope with steadily increasing data from advanced microscopy. We describe here the Fiji macro 3D ART VeSElecT which we developed to study synaptic vesicles in electron tomograms. We apply this tool to quantify vesicle properties (i) in embryonic Danio rerio 4 and 8 days past fertilization (dpf) and (ii) to compare Caenorhabditis elegans N2 neuromuscular junctions (NMJ) wild-type and its septin mutant (unc-59(e261)). We demonstrate development-specific and mutant-specific changes in synaptic vesicle pools in both models...
January 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28053031/muscle-fibers-secrete-fgfbp1-to-slow-degeneration-of-neuromuscular-synapses-during-aging-and-progression-of-als
#14
Thomas Taetzsch, Milagros J Tenga, Gregorio Valdez
: The identity of muscle secreted factors critical for the development and maintenance of neuromuscular junctions (NMJs) remains largely unknown. Here, we show that muscle fibers secrete and concentrate the fibroblast growth factor binding protein 1 (FGFBP1) at NMJs. Although FGFBP1 expression increases during development, its expression decreases before NMJ degeneration during aging and in SOD1(G93A) mice, a mouse model for amyotrophic lateral sclerosis (ALS). Based on these findings, we examined the impact of deleting FGFBP1 on NMJs...
January 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28042994/assessing-neuromuscular-junction-stability-from-stimulated-emg-in-children
#15
Matthew C Pitt, John C Mchugh, Jacquie Deeb, Ralph A Smith
OBJECTIVE: We present our 9-year experience of stimulated EMG potential analysis using concentric electrodes (SPACE) to evaluate neuromuscular junction (NMJ) disorders in awake children. The technique uses high frequency filtration of stimulated motor unit potentials and applies peak detection software to estimate mean consecutive difference (MCD). METHODS: SPACE was carried out in orbicularis oculi of 878 children (377 girls; median age 47months) between 2007 and 2015, stimulating the facial nerve with a monopolar cathode...
February 2017: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
https://www.readbyqxmd.com/read/27998908/loss-of-laminin-%C3%AE-4-results-in-pre-and-postsynaptic-modifications-at-the-neuromuscular-junction
#16
Kirat K Chand, Kah Meng Lee, Nickolas A Lavidis, Peter G Noakes
Synaptic basal lamina such as laminin-421 (α4β2γ1) mediate differentiation of the neuromuscular junction (NMJ). Laminins interact with their pre- or postsynaptic receptors to provide stability and alignment of the pre- to postsynaptic specializations. Knockout of the lama4 gene does not alter gross NMJ morphogenesis. However, mice deficient in laminin-α4 (lama4(-/-)) display disruptions in the alignment of the active zones and postsynaptic folds at the NMJ, although the physiological consequences of this loss have not been examined...
December 20, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27966543/limb-girdle-myasthenia-with-digenic-rapsn-and-a-novel-disease-gene-ak9-mutations
#17
Ching-Wan Lam, Ka-Sing Wong, Ho-Wan Leung, Chun-Yiu Law
Though dysfunction of neuromuscular junction (NMJ) is associated with congenital myasthenic syndrome (CMS), the proteins involved in neuromuscular transmission have not been completely identified. In this study, we aimed to identify a novel CMS gene in a consanguineous family with limb-girdle type CMS. Homozygosity mapping of the novel CMS gene was performed using high-density single-nucleotide polymorphism microarrays. The variants in CMS gene were identified by whole-exome sequencing (WES) and Sanger sequencing...
February 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/27964993/laminin-is-instructive-and-calmodulin-dependent-kinase-ii-is-non-permissive-for-the-formation-of-complex-aggregates-of-acetylcholine-receptors-on-myotubes-in-culture
#18
Raphael Vezina-Audette, Mathieu Tremblay, Salvatore Carbonetto
Previous work has shown that myotubes cultured on laminin-coated substrates form complex aggregates of synaptic proteins that are similar in shape and composition to neuromuscular junctions (NMJs). Here we show that laminin instructs the location of complex aggregates which form only on the lower surface when laminin is coated onto culture dishes but over the entire cell when laminin is added in solution. Silencing of myotubes by agents that block electrical activity (tetrodotoxin, verapamil) or by inhibitors of calmodulin dependent kinase (CaMKII) render the myotube permissive for the formation of complex aggregates...
December 10, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/27943179/a-cell-culture-system-to-investigate-the-presynaptic-control-of-subsynaptic-membrane-differentiation-at-the-neuromuscular-junction
#19
Nadine Schmidt, Sreya Basu, Stephan Kröger, Hans Rudolf Brenner
For decades the neuromuscular junction (NMJ) has been a favorite preparation to investigate basic mechanisms of synaptic function and development. As its function is to transmit action potentials in a 1:1 ratio from motor neurons to muscle fibers, the NMJ shows little or no functional plasticity, a property that makes it poorly suited to investigate mechanisms of use-dependent adaptations of synaptic function, which are thought to underlie learning and memory formation in the brain. On the other hand, the NMJ is unique in that the differentiation of the subsynaptic membrane is regulated by one major factor secreted from motor neurons, agrin...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27939356/the-origins-of-rimmed-vacuoles-and-granulovacuolar-degeneration-bodies-are-associated-with-the-wnt-signaling-pathway
#20
Yukari Murata-Shinozaki, Tetsuya Takahashi, Tomoyasu Matsubara, Hirofumi Maruyama, Yuishin Izumi, Masayasu Matsumoto
Inclusion-body myositis (IBM) and Alzheimer's disease (AD) are biochemically characterized by the presence of aggregated β-amyloid protein and tau protein. In addition, both diseases are pathologically characterized by vacuolar changes, including rimmed vacuoles (RVs) in IBM and granulovacuolar degeneration (GVD) in AD. Previously, we demonstrated that RVs and GVD bodies are associated with a set of common molecules, leading us to speculate that both RVs and GVD bodies originate from similar structures on the plasma membrane of muscle cells and neuronal cells, namely, the neuromuscular junction (NMJ) and the postsynaptic spine especially in terms of Wnt signaling pathway...
December 7, 2016: Neuroscience Letters
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