当前位置： SCI文献检索 > MOLECULAR PHARMACOLOGY期刊下所有文献 > ATP induces synaptic gene expressions in cortical neurons: transduction and transcription control via P2Y1 receptors.

ATP induces synaptic gene expressions in cortical neurons: transduction and transcription control via P2Y1 receptors.

Abstract：

:Studies in vertebrate neuromuscular synapses have revealed previously that ATP, via P2Y receptors, plays a critical role in regulating postsynaptic gene expressions. An equivalent regulatory role of ATP and its P2Y receptors would not necessarily be expected for the very different situation of the brain synapses, but we provide evidence here for a brain version of that role. In cultured cortical neurons, the expression of P2Y(1) receptors increased sharply during neuronal differentiation. Those receptors were found mainly colocalized with the postsynaptic scaffold postsynaptic density protein 95 (PSD-95). This arises through a direct interaction of a PDZ domain of PSD-95 with the C-terminal PDZ-binding motif, D-T-S-L of the P2Y(1) receptor, confirmed by the full suppression of the colocalization upon mutation of two amino acids therein. This interaction is effective in recruiting PSD-95 to the membrane. Specific activation of P2Y(1) (G-protein-coupled) receptors induced the elevation of intracellular Ca(2+) and activation of a mitogen-activated protein kinase/Raf-1 signaling cascade. This led to distinct up-regulation of the genes encoding acetylcholinesterase (AChE(T) variant), choline acetyltransferase, and the N-methyl-d-aspartate receptor subunit NR2A. This was confirmed, in the example of AChE, to arise from P2Y(1)-dependent stimulation of a human ACHE gene promoter. That involved activation of the transcription factor Elk-1; mutagenesis of the ACHE promoter revealed that Elk-1 binding at its specific responsive elements in that promoter was induced by P2Y(1) receptor activation. The combined findings reveal that ATP, via its P2Y(1) receptor, can act trophically in brain neurons to regulate the gene expression of direct effectors of synaptic transmission.

journal_name

Mol Pharmacol

journal_title

Molecular pharmacology

authors

Siow NL,Choi RC,Xie HQ,Kong LW,Chu GK,Chan GK,Simon J,Barnard EA,Tsim KW

doi

10.1124/mol.110.066506

subject

Has Abstract

pub_date

2010-12-01 00:00:00

pages

1059-71

issue

eissn

0026-895X

issn

1521-0111

pii

mol.110.066506

journal_volume

pub_type

杂志文章

在线工具

ATP induces synaptic gene expressions in cortical neurons: transduction and transcription control via P2Y1 receptors.