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PMID:17706883

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Citation

Ryten, M, Koshi, R, Knight, GE, Turmaine, M, Dunn, P, Cockayne, DA, Ford, AP and Burnstock, G (2007) Abnormalities in neuromuscular junction structure and skeletal muscle function in mice lacking the P2X2 nucleotide receptor. Neuroscience 148:700-11

Abstract

ATP is co-released in significant quantities with acetylcholine from motor neurons at skeletal neuromuscular junctions (NMJ). However, the role of this neurotransmitter in muscle function remains unclear. The P2X2 ion channel receptor subunit is expressed during development of the skeletal NMJ, but not in adult muscle fibers, although it is re-expressed during muscle fiber regeneration. Using mice deficient for the P2X2 receptor subunit for ATP (P2X2(-/-)), we demonstrate a role for purinergic signaling in NMJ development. Whereas control NMJs were characterized by precise apposition of pre-synaptic motor nerve terminals and post-synaptic junctional folds rich in acetylcholine receptors (AChRs), NMJs in P2X2(-/-) mice were disorganized: misapposition of nerve terminals and post-synaptic AChR expression localization was common; the density of post-synaptic junctional folds was reduced; and there was increased end-plate fragmentation. These changes in NMJ structure were associated with muscle fiber atrophy. In addition there was an increase in the proportion of fast type muscle fibers. These findings demonstrate a role for P2X2 receptor-mediated signaling in NMJ formation and suggest that purinergic signaling may play an as yet largely unrecognized part in synapse formation.

Links

PubMed Online version:10.1016/j.neuroscience.2007.06.050

Keywords

Acetylcholine/metabolism; Adenosine Triphosphate/metabolism; Animals; Cell Differentiation/genetics; Female; Gene Expression Regulation, Developmental/genetics; Mice; Mice, Knockout; Microscopy, Electron, Transmission; Motor Neurons/metabolism; Motor Neurons/pathology; Muscle, Skeletal/abnormalities; Muscle, Skeletal/innervation; Muscle, Skeletal/physiopathology; Neuromuscular Junction/abnormalities; Neuromuscular Junction/metabolism; Neuromuscular Junction/physiopathology; Presynaptic Terminals/metabolism; Presynaptic Terminals/pathology; Receptors, Purinergic P2/genetics; Receptors, Purinergic P2X2; Signal Transduction/genetics; Synapses/metabolism; Synapses/pathology; Synaptic Membranes/metabolism; Synaptic Membranes/pathology; Synaptic Transmission/genetics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:P2RX2

acts_upstream_of_or_within

GO:0007528: neuromuscular junction development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2687349

P

Seeded From UniProt

complete

MOUSE:P2RX2

located_in

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:P2RX2

acts_upstream_of_or_within

GO:0048741: skeletal muscle fiber development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2687349

P

  • occurs_in:(EMAPA:35578)

Seeded From UniProt

complete

See also

References

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