Disease relevance of Neuromuscular Junction

• These data suggest that the pathogenesis of myasthenia gravis often involves and antibody-mediated autoimmune attack on the acetylcholine receptors of the neuromuscular junction [1].
• It has been suggested that the augmentation of noradrenaline concentration at the neuromuscular junctions following the inhibition of its uptake may contribute to the ouabain-induced cardiac arrhythmia seen with toxic doses of the drug [2].
• The transgenic mice exhibited gradually increasing muscular weakness, flaccid paralysis, and functional disruption of the neuromuscular junction that was reversed after administration of an inhibitor of acetylcholinesterase, features which are strikingly similar to human MG [3].
• The pharmacological specificity of Ca2+ channel-secretion coupling in acetylcholine (ACh) and somatostatin (SOM) release was studied in the chick eye choroid neuromuscular junctions and in dissociated ciliary ganglion (CG) neurons [4].
• Transgenic expression of the alpha 7BX2 chain in the mdx/utr(-/-) mice extended their longevity by threefold, reduced kyphosis and the development of muscle disease, and maintained mobility and the structure of the neuromuscular junction [5].

Psychiatry related information on Neuromuscular Junction

• We demonstrate that presynaptic changes in Rho activity at Caenorhabditis elegans neuromuscular junctions can radically change animal behavior via modulation of two separate pathways [6].
• Amyloid precursor protein (APP), associated with Alzheimer's disease plaques, is known to be present in synapses of the brain and in the adult neuromuscular junction (NMJ) [7].

High impact information on Neuromuscular Junction

• Quantal acetylcholine release at the vertebrate neuromuscular junction [8].
• Agrin, through its interaction with the receptor tyrosine kinase MuSK, mediates accumulation of acetylcholine receptors (AChR) at the developing neuromuscular junction [9].
• Utrophin, a homolog of dystrophin, is confined to the postsynaptic membrane at skeletal neuromuscular junctions and has been implicated in synaptic development [10].
• Mice lacking either agrin or MuSK have recently been generated and exhibit similarly profound defects in their neuromuscular junctions [11].
• The receptor tyrosine kinase MuSK is required for neuromuscular junction formation in vivo [12].

Chemical compound and disease context of Neuromuscular Junction

• The neuromodulator adenosine is known to decrease neurotransmitter release at the neuromuscular junction by activation of an A1 adenosine receptor coupled to a pertussis toxin-sensitive G protein [13].
• The neuromuscular junction nicotinic acetylcholine receptor (AChR), a pentameric membrane glycoprotein, is the autoantigen involved in the autoimmune disease myasthenia gravis (MG) [14].
• Using the cat soleus nerve-muscle preparation, intravenous neostigmine doses between 20-200 micrograms/kg evoked fasciculations in a dose-related manner [15].
• The neurotoxocity of RNA-free lipopolysaccharide (LPS) extracted from Salmonella Typhimurium (SR-11) was tested at the frog neuromuscular junction using intracellular recording techniques [16].
• Diaphragmatic paralysis was accomplished by a bolus injection of vecuronium, a neuromuscular junction blocker, into the left phrenic artery of an in situ vascularly isolated and innervated left diaphragm [17].

Biological context of Neuromuscular Junction

• Here we report that when calcium influx is blocked by cobalt or manganese ions in a calcium-free Ringer, as measured with Fura-2, and [Ca2+]i is elevated by liberation from a caged calcium compound, transmitter release at the crayfish neuromuscular junction is unaffected by presynaptic action potentials [18].
• Here we show that the neural t-SNARE (target-membrane-associated-soluble N-ethylmaleimide fusion protein attachment protein (SNAP) receptor) SNAP-25 is not required for nerve growth or stimulus-independent neurotransmitter release, but is essential for evoked synaptic transmission at neuromuscular junctions and central synapses [19].
• Tyrosine phosphorylation of the AChR occurred late in the development of the neuromuscular junction, between postnatal days 7 and 14 [20].
• These results suggest that ARIA performs a vital role by directing spatially restricted gene expression at the neuromuscular junction [21].
• Regulation of retrograde signaling at neuromuscular junctions by the novel C2 domain protein AEX-1 [22].

Anatomical context of Neuromuscular Junction

• S-laminin, a novel homolog of laminin, is concentrated in a subset of basal laminae including the basal lamina that passes between motor nerve terminals and muscle fibers at the neuromuscular junction [23].
• This finding, together with the observation that basal lamina directs the formation of both AChR and AChE aggregates at regenerating neuromuscular junctions in vivo, leads us to hypothesize that a single component of the synaptic basal lamina causes the formation of both these synaptic specializations on regenerating myofibres [24].
• Insects and other invertebrates use glutamate as a neurotransmitter in the central nervous system and at the neuromuscular junction [25].
• We now demonstrate that agrin, an aggregating protein crucial for formation of the neuromuscular junction, is also expressed in lymphocytes and is important in reorganization of membrane lipid microdomains and setting the threshold for T cell signaling [26].
• Agrin is best known as a crucial organizer of postsynaptic differentiation at the neuromuscular junction, but it has recently also been implicated in the formation of the immunological synapse, the organization of the cytoskeleton and the amelioration of function in diseased muscle [27].

Associations of Neuromuscular Junction with chemical compounds

• The acetylcholine receptor at the neuromuscular junction [28].
• Postsynaptic effects of ethanol at the frog neuromuscular junction [29].
• We report here that the formamidine acaricide/insecticide, chlordimeform (CDM), and its demethylated deivative can mimic the actions of octopamine at the locust neuromuscular junctions [30].
• Calcium-dependent presynaptic action of substance P at the frog neuromuscular junction [31].
• In normal muscle, lithium reduces the number of acetylcholine receptors at neuromuscular junctions [32].

Gene context of Neuromuscular Junction

• Dystrophin-related protein (DRP or 'utrophin') is localized in normal adult muscle primarily at the neuromuscular junction [33].
• On i.c.v. delivery, Vegf is anterogradely transported and preserves neuromuscular junctions in SOD1(G93A) rats [34].
• Postsynaptic requirement for Abl kinases in assembly of the neuromuscular junction [35].
• Agrin-induced clustering of acetylcholine receptors (AChRs) in the postsynaptic membrane is a key step in synaptogenesis at the neuromuscular junction [36].
• We have previously shown that collagen Q (ColQ) anchors AChE at the neuromuscular junction [37].

Analytical, diagnostic and therapeutic context of Neuromuscular Junction

• The turnover rate of acetylcholine receptors at neuromuscular junctions in mice increases progressively after denervation and, after 15 days, reaches a half-time of 30 z 5 hours [38].
• Immunofluorescence microscopy localized DRP almost exclusively to the neuromuscular junction region in rabbit and mouse skeletal muscle, as well as mdx mouse muscle and denervated mouse muscle [39].
• We have used immunogold electron microscopy to study the organization of the acetylcholine receptor, 43 kd protein, voltage-sensitive Na+ channel, and ankyrin in the postsynaptic membrane of the rat neuromuscular junction [40].
• The distribution of the synaptic vesicle-associated phosphoprotein synapsin I after electrical stimulation of the frog neuromuscular junction was investigated by immunogold labeling and compared with the distribution of the integral synaptic vesicle protein synaptophysin [41].
• D-endoA is recruited to the sites of endocytosis, as revealed by immunocytochemistry of the neuromuscular junction (NMJ) of mutant L3 larvae carrying the temperature-sensitive allele of dynamin, shibire [42].

References