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Title: ATP potentiates agrin-induced AChR aggregation in cultured myotubes
Authors: Ling, Karen K. Y.
Siow, Nina L.
Choi, Chi Yan
Ting, Annie K. L.
Kong, Ling W.
Tsim, Karl Wah-Keung
Keywords: Nucleotide receptor
Guanosine triphosphatase
Neuromuscular junctions
Cultured myotubes
Issue Date: Jul-2004
Citation: Journal of biological chemistry, v. 279, no. 30, Jul. 2004, p. 31081-31088
Abstract: At vertebrate neuromuscular junctions, ATP is known to stabilize acetylcholine in the synaptic vesicles and to be co-released with it. We have shown previously that a nucleotide receptor, P2Y1 receptor, is localized at the nmjs, and we propose that this mediates a trophic role for synaptic ATP there. In cultured myotubes, the activation of P2Y1 receptors modulated agrin-induced acetylcholine receptor (AChR) aggregation in a potentiation manner. This potentiation effect in agrin-induced AChR aggregation was reduced by antagonizing the P2Y1 receptors. The guanosine triphosphatase RhoA was shown to be responsible for this P2Y1-potentiated effect. The localization of RhoA in rat and chicken skeletal muscles was restricted at the neuromuscular junctions. Application of P2Y1 agonists in cultured myotubes induced RhoA activation, which showed an additive effect with agrin-induced RhoA activation. Over-expression of dominant-negative mutant of RhoA in cultured myotubes diminished the agrin-induced AChR aggregation, as well as the potentiation effect of P2Y1-specific agonist. Application of UTP in the cultures also triggered similar responses as did 2-methylthioadenosine 5'-diphosphate, suggesting the involvement of other subtypes of P2Y receptors. These results demonstrate that RhoA could serve as a downstream mediator of signaling mediated by P2Y1 receptor and agrin, which therefore synergizes the effects of the two neuron-derived trophic factors in modulating the formation and/or maintenance of post-synaptic apparatus at the neuromuscular junctions.
Rights: We would like to give credit to American Society for Biochemistry and Molecular Biology for granting us permission to repost this article
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