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Adenosine A 2A receptors permit mG luR5‐evoked tyrosine phosphorylation of NR 2B (Tyr1472) in rat hippocampus: a possible key mechanism in NMDA receptor modulation
Author(s) -
Sarantis Konstantinos,
Tsiamaki Eirini,
Kouvaros Stylianos,
Papatheodoropoulos Costas,
Angelatou Fevronia
Publication year - 2015
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13291
Subject(s) - metabotropic glutamate receptor 5 , nmda receptor , long term depression , metabotropic glutamate receptor , synaptic plasticity , neuroscience , metabotropic receptor , glutamate receptor , metabotropic glutamate receptor 1 , tyrosine phosphorylation , microbiology and biotechnology , metabotropic glutamate receptor 6 , biology , chemistry , phosphorylation , receptor , ampa receptor , biochemistry
Abstract A great body of evidence points toward a functional interaction between metabotropic glutamate 5 receptors ( mG luR5) and NMDA receptors ( NMDAR ) that enhances synaptic plasticity and cognition. However, the molecular mechanism underlying this interaction remains unclear. Here, we show that co‐activation of mG luR5 and NMDAR in hippocampal slices synergistically leads to a robust phosphorylation of NR 2B (Tyr1472), which is Src kinase dependent and is enabled by endogenous adenosine acting on A 2A receptors. As it is well known, NR 2B (Tyr1472) phosphorylation anchors NR 2B‐containing NMDAR s to the surface of post‐synaptic membranes, preventing their internalization. This is supported by our electrophysiological experiments showing that co‐activation of mG luR5 and NMDAR s robustly enhances NMDAR ‐dependent neuronal excitability recorded in CA 1 hippocampal region, which temporally coincides with the robust increase in NR 2B (Tyr1472) phosphorylation, depends on Src kinases and is also permitted by A 2A receptors. Thus, we strongly suggest that NR 2B (Tyr1472) phosphorylation constitutes, at least to some extent, the molecular mechanism underlying the mG luR5‐mediated enhancement of NMDAR ‐dependent responses, which is modulated by A 2A receptors. A better understanding of the molecular basis of mG luR5/ NMDAR interaction would elucidate their role in synaptic plasticity processes as well as in pathological conditions.We propose the following molecular mechanism by which metabotropic Glutamate Receptor 5 (mGluR5) potentiate ionotropic Glutamate N ‐Methyl‐D‐Aspartate Receptor (NMDAR) responses in rat hippocampus. Co‐activation of mGLUR5/NMDAR activates Src kinases, leading to NR2B(Tyr1472) phosphorylation, which anchors NR2B‐containing NMDAR to the plasma membrane, thus inducing a robust increase in the NMDA‐dependent excitability. Interestingly, adenosine A 2A receptors license the mGluR5‐induced NR2B(Tyr1472) phosphorylation.