QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, June 1, 2003, 23(11):4445-4456

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (33) Citing Articles via Google Scholar Google Scholar Articles by Choi, R. C. Y. Articles by Tsim, K. W. K. Search for Related Content PubMed PubMed Citation Articles by Choi, R. C. Y. Articles by Tsim, K. W. K.

 Previous Article  |  Next Article 

ATP Acts via P2Y₁ Receptors to Stimulate Acetylcholinesterase and Acetylcholine Receptor Expression: Transduction and Transcription Control

Roy C. Y. Choi,¹ Nina L. Siow,¹ Anthony W. M. Cheng,¹ Karen K. Y. Ling,¹ Edmund K. K. Tung,¹ Joseph Simon,² Eric A. Barnard,² and Karl W. K. Tsim¹

¹ Department of Biology and Molecular Neuroscience Center, Hong Kong University of Science and Technology, Hong Kong, China, and ² Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, United Kingdom

At the vertebrate neuromuscular junction 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, the P2Y₁ receptor, is localized at the junction, and we propose that this mediates a trophic role for synaptic ATP there. Evidence in support of this and on its mechanism is given here. With the use of chick or mouse myotubes expressing promoter–reporter constructs from genes of acetylcholinesterase (AChE) or of the acetylcholine receptor subunits, P2Y₁ receptor agonists were shown to stimulate the transcription of each of those genes. The pathway to activation of the AChE gene was shown to involve protein kinase C and intracellular Ca ²⁺ release. Application of dominant-negative or constitutively active mutants, or inhibitors of specific kinases, showed that it further proceeds via some of the known intermediates of extracellular signal-regulated kinase phosphorylation. In both chick and mouse myotubes this culminates in activation of the transcription factor Elk-1, confirmed by gel mobility shift assays and by the nuclear accumulation of phosphorylated Elk-1. All of the aforementioned activations by agonist were amplified when the content of P2Y₁ receptors was boosted by transfection, and the activations were blocked by a P2Y₁-selective antagonist. Two Elk-1 binding site sequences present in the AChE gene promoter were jointly sufficient to drive ATP-induced reporter gene transcription. Thus ATP regulates postsynaptic gene expression via a pathway to a selective transcription factor activation.

Key words: acetylcholine receptor; acetylcholinesterase; ATP receptors; P2Y₁receptor; neuromuscular junction; trophic factors; gene regulation; Elk-1

---

Received Oct. 28, 2002; revised Mar. 11, 2003; accepted Mar. 13, 2003.

This article has been cited by other articles:

				R. C. Y. Choi, J. Simon, K. W. K. Tsim, and E. A. Barnard Constitutive and Agonist-induced Dimerizations of the P2Y1 Receptor: RELATIONSHIP TO INTERNALIZATION AND SCAFFOLDING J. Biol. Chem., April 18, 2008; 283(16): 11050 - 11063. [Abstract] [Full Text] [PDF]

				S. Camp, A. De Jaco, L. Zhang, M. Marquez, B. De La Torre, and P. Taylor Acetylcholinesterase Expression in Muscle Is Specifically Controlled by a Promoter-Selective Enhancesome in the First Intron J. Neurosci., March 5, 2008; 28(10): 2459 - 2470. [Abstract] [Full Text] [PDF]

				W. Lu, D. Reigada, J. Sevigny, and C. H. Mitchell Stimulation of the P2Y1 Receptor Up-Regulates Nucleoside-Triphosphate Diphosphohydrolase-1 in Human Retinal Pigment Epithelial Cells J. Pharmacol. Exp. Ther., October 1, 2007; 323(1): 157 - 164. [Abstract] [Full Text] [PDF]

				G. Burnstock Physiology and Pathophysiology of Purinergic Neurotransmission Physiol Rev, April 1, 2007; 87(2): 659 - 797. [Abstract] [Full Text] [PDF]

				M. P. Abbracchio, G. Burnstock, J.-M. Boeynaems, E. A. Barnard, J. L. Boyer, C. Kennedy, G. E. Knight, M. Fumagalli, C. Gachet, K. A. Jacobson, et al. International Union of Pharmacology LVIII: Update on the P2Y G Protein-Coupled Nucleotide Receptors: From Molecular Mechanisms and Pathophysiology to Therapy Pharmacol. Rev., September 1, 2006; 58(3): 281 - 341. [Abstract] [Full Text] [PDF]

				D. Yeung, K. Zablocki, C.-F. Lien, T. Jiang, S. Arkle, W. Brutkowski, J. Brown, H. Lochmuller, J. Simon, E. A. Barnard, et al. Increased susceptibility to ATP via alteration of P2X receptor function in dystrophic mdx mouse muscle cells FASEB J, April 1, 2006; 20(6): 610 - 620. [Abstract] [Full Text] [PDF]

				L. M. Angus, J. V. Chakkalakal, A. Mejat, J. K. Eibl, G. Belanger, L. A. Megeney, E. R. Chin, L. Schaeffer, R. N. Michel, and B. J. Jasmin Calcineurin-NFAT signaling, together with GABP and peroxisome PGC-1{alpha}, drives utrophin gene expression at the neuromuscular junction Am J Physiol Cell Physiol, October 1, 2005; 289(4): C908 - C917. [Abstract] [Full Text] [PDF]

				A. R. Giniatullin, S. N. Grishin, E. R. Sharifullina, A. M. Petrov, A. L. Zefirov, and R. A. Giniatullin Reactive oxygen species contribute to the presynaptic action of extracellular ATP at the frog neuromuscular junction J. Physiol., May 15, 2005; 565(1): 229 - 242. [Abstract] [Full Text] [PDF]

				E. K. K. Tung, R. C. Y. Choi, N. L. Siow, J. X. S. Jiang, K. K. Y. Ling, J. Simon, E. A. Barnard, and K. W. K. Tsim P2Y2 Receptor Activation Regulates the Expression of Acetylcholinesterase and Acetylcholine Receptor Genes at Vertebrate Neuromuscular Junctions Mol. Pharmacol., October 1, 2004; 66(4): 794 - 806. [Abstract] [Full Text] [PDF]

				K. K. Y. Ling, N. L. Siow, R. C. Y. Choi, A. K. L. Ting, L. W. Kong, and K. W. K. Tsim ATP Potentiates Agrin-induced AChR Aggregation in Cultured Myotubes: ACTIVATION OF RHOA IN P2Y1 NUCLEOTIDE RECEPTOR SIGNALING AT VERTEBRATE NEUROMUSCULAR JUNCTIONS J. Biol. Chem., July 23, 2004; 279(30): 31081 - 31088. [Abstract] [Full Text] [PDF]

				H. H. C. Lee, R. C. Y. Choi, A. K. L. Ting, N. L. Siow, J. X. S. Jiang, J. Massoulie, and K. W. K. Tsim Transcriptional Regulation of Acetylcholinesterase-associated Collagen ColQ: DIFFERENTIAL EXPRESSION IN FAST AND SLOW TWITCH MUSCLE FIBERS IS DRIVEN BY DISTINCT PROMOTERS J. Biol. Chem., June 25, 2004; 279(26): 27098 - 27107. [Abstract] [Full Text] [PDF]

				J. X. S. Jiang, R. C. Y. Choi, N. L. Siow, H. H. C. Lee, D. C. C. Wan, and K. W. K. Tsim Muscle Induces Neuronal Expression of Acetylcholinesterase in Neuron-Muscle Co-culture: TRANSCRIPTIONAL REGULATION MEDIATED BY cAMP-DEPENDENT SIGNALING J. Biol. Chem., November 14, 2003; 278(46): 45435 - 45444. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help