Article

Disruption of TrkB-Mediated Signaling Induces Disassembly of Postsynaptic Receptor Clusters at Neuromuscular Junctions

Department of Neuroscience University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Neuron (Impact Factor: 15.05). 12/1999; 24(3):567-83. DOI: 10.1016/S0896-6273(00)81113-7
Source: PubMed

ABSTRACT

Neurotrophins and tyrosine receptor kinase (Trk) receptors are expressed in skeletal muscle, but it is unclear what functional role Trk-mediated signaling plays during postnatal life. Full-length TrkB (trkB.FL) as well as truncated TrkB (trkB.t1) were found to be localized primarily to the postsynaptic acetylcholine receptor- (AChR-) rich membrane at neuromuscular junctions. In vivo, dominant-negative manipulation of TrkB signaling using adenovirus to overexpress trkB.t1 in mouse sternomastoid muscle fibers resulted in the disassembly of postsynaptic AChR clusters at neuromuscular junctions, similar to that observed in mutant trkB+/- mice. When TrkB-mediated signaling was disrupted in cultured myotubes in the absence of motor nerve terminals and Schwann cells, agrin-induced AChR clusters were also disassembled. These results demonstrate a novel role for neurotrophin signaling through TrkB receptors on muscle fibers in the ongoing maintenance of postsynaptic AChR regions.

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    • "It is known that A2A receptors, at motor nerve terminals, trigger the action of BDNF [29], which enhances transmitter release at developing neuromuscular junctions [33], improving neuromuscular transmission in the adult rat diaphragm [34] and facilitating synaptic efficacy by increasing presynaptic depolarization at the neuromuscular junction [35]. BDNF is also important for maintenance of ACh receptor clustering in the endplate [36], [37]. Whether the enhancement by A2A receptor in the pre-symptomatic phase of the disease, could account for the potentiation of endogenous BDNF actions that might occur at the neuromuscular junction, therefore, enhancing synaptic transmission and compensating an eventual early denervation needs to be investigated. "
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    No preview · Article · May 2014 · Journal of Neuroscience Research
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