Disruption of Trkb-mediated signaling induces disassembly of postsynaptic receptor clusters at neuromuscular junctions.
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.
Gonzalez
M
M
Department of Neuroscience University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Ruggiero
F P
FP
Chang
Q
Q
Shi
Y J
YJ
Rich
M M
MM
Kraner
S
S
Balice-Gordon
R J
RJ
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D005799:Genes, Dominant; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000502:physiology; D009414:Nerve Growth Factors / Q000502:physiology; D009469:Neuromuscular Junction / Q000378:metabolism*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011940:Receptor Aggregation / Q000502:physiology*; D020813:Receptor, trkB / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011950:Receptors, Cholinergic / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D010446:Peptide Fragments; D011950:Receptors, Cholinergic; D020813:Receptor, trkB