| http://purl.uniprot.org/citations/30870432 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/30870432 | http://www.w3.org/2000/01/rdf-schema#comment | "Schwann cells are integral components of vertebrate neuromuscular synapses; in their absence, pre-synaptic nerve terminals withdraw from post-synaptic muscles, leading to muscle denervation and synapse loss at the developing neuromuscular junction (NMJ). Here, we report a rescue of muscle denervation and neuromuscular synapses loss in type III Neuregulin 1 mutant mice (CRD-Nrg1-/-), which lack Schwann cells. We found that muscle denervation and neuromuscular synapse loss were prevented in CRD-Nrg1-/-mice when presynaptic activity was blocked by ablating a specific gene, such as Snap25 (synaptosomal-associated 25 kDa protein) or Chat (choline acetyltransferase). Further, these effects were mediated by a pathway that requires postsynaptic acetylcholine receptors (AChRs), because ablating Chrna1 (acetylcholine receptor α1 subunit), which encodes muscle-specific AChRs in CRD-Nrg1-/-mice also rescued muscle denervation. Moreover, genetically ablating muscle dihydropyridine receptor (DHPR) β1 subunit (Cacnb1) or ryanodine receptor 1 (Ryr1) also rescued muscle denervation and neuromuscular synapse loss in CRD-Nrg1-/-mice. Thus, these genetic manipulations follow a pathway-from presynaptic to postsynaptic, and, ultimately to muscle activity mediated by DHPRs and Ryr1. Importantly, electrophysiological analyses reveal robust synaptic activity in the rescued, Schwann-cell deficient NMJs in CRD-Nrg1-/-Cacnb1-/-or CRD-Nrg1-/-Ryr1-/-mutant mice. Thus, a blockade of synaptic activity, although sufficient, is not necessary to preserve NMJs that lack Schwann cells. Instead, a blockade of muscle activity mediated by DHRPs and Ryr1 is both necessary and sufficient for preserving NMJs that lack Schwann cells. These findings suggest that muscle activity mediated by DHPRs/Ryr1 may destabilize developing NMJs and that Schwann cells play crucial roles in counteracting such a destabilizing activity to preserve neuromuscular synapses during development."xsd:string |
| http://purl.uniprot.org/citations/30870432 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pgen.1007857"xsd:string |
| http://purl.uniprot.org/citations/30870432 | http://purl.uniprot.org/core/author | "Chen F."xsd:string |
| http://purl.uniprot.org/citations/30870432 | http://purl.uniprot.org/core/author | "Liu Y."xsd:string |
| http://purl.uniprot.org/citations/30870432 | http://purl.uniprot.org/core/author | "Lin W."xsd:string |
| http://purl.uniprot.org/citations/30870432 | http://purl.uniprot.org/core/author | "Ye Q."xsd:string |
| http://purl.uniprot.org/citations/30870432 | http://purl.uniprot.org/core/author | "Sugiura Y."xsd:string |
| http://purl.uniprot.org/citations/30870432 | http://purl.uniprot.org/core/author | "Lee K.F."xsd:string |
| http://purl.uniprot.org/citations/30870432 | http://purl.uniprot.org/core/date | "2019"xsd:gYear |
| http://purl.uniprot.org/citations/30870432 | http://purl.uniprot.org/core/name | "PLoS Genet"xsd:string |
| http://purl.uniprot.org/citations/30870432 | http://purl.uniprot.org/core/pages | "e1007857"xsd:string |
| http://purl.uniprot.org/citations/30870432 | http://purl.uniprot.org/core/title | "Blocking skeletal muscle DHPRs/Ryr1 prevents neuromuscular synapse loss in mutant mice deficient in type III Neuregulin 1 (CRD-Nrg1)."xsd:string |
| http://purl.uniprot.org/citations/30870432 | http://purl.uniprot.org/core/volume | "15"xsd:string |
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