ATP induces the post-synaptic gene expression in neuron-neuron synapses: Transcriptional regulation of AChE catalytic subunit.
Adenosine 5'-triphosphate (ATP) is an important trophic factor, which is co-stored and co-released at central and peripheral cholinergic synapses. The synaptic ATP induces post-synaptic gene transcription during the formation and maintenance of vertebrate neuromuscular junction (nmj) via a mitogen-activaton protein (MAP) kinase signaling pathway and subsequently activates acetylcholinesterase (AChE) and acetylcholine receptor (AChR) genes. However, the role of ATP in the central nervous system is still not clear. Primary culture of rat cortical neurons was used as a model system to study the biological functions of ATP in neuron-neuron synapses. During the differentiation of cultured cortical neurons, the protein levels of AChE and one of the ATP receptor subtypes, P2Y1 receptor, were increased. By using a human AChE promoter tagged with a luciferase-reporter gene, the transcriptional regulation of AChE gene by ATP could be monitored. The activation of P2Y1 receptors could regulate the AChE promoter activity in cultured cortical neurons. These results suggested the activation of P2Y receptors may play role(s) in synaptic gene expression of neuron-neuron synapses in the brain.
Siow
Nina L
NL
Department of Biology, The Hong Kong University of Science and Technology, Clear Water Bay Road, Hong Kong, China. nina@ust.hk <nina@ust.hk>
Xie
Heidi Q
HQ
Choi
Roy C Y
RC
Tsim
Karl W K
KW
D000110:Acetylcholinesterase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002384:Catalysis; D020134:Catalytic Domain / Q000235:genetics*; D002454:Cell Differentiation; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D011401:Promoter Regions, Genetic / Q000235:genetics; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058472:Receptors, Purinergic P2Y1; D013569:Synapses / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects
C546382:P2RY1 protein, human; C546384:P2ry1 protein, rat; D021122:Protein Subunits; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D000255:Adenosine Triphosphate; D000110:Acetylcholinesterase