PMID- 26303340
OWN - NLM
STAT- MEDLINE
DCOM- 20160216
LR  - 20151106
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Linking)
VI  - 135
IP  - 4
DP  - 2015 Nov
TI  - Adenosine A(2)A receptors permit mGluR5-evoked tyrosine phosphorylation of NR2B 
      (Tyr1472) in rat hippocampus: a possible key mechanism in NMDA receptor 
      modulation.
PG  - 714-26
LID - 10.1111/jnc.13291 [doi]
AB  - A great body of evidence points toward a functional interaction between 
      metabotropic glutamate 5 receptors (mGluR5) 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 
      mGluR5 and NMDAR in hippocampal slices synergistically leads to a robust 
      phosphorylation of NR2B (Tyr1472), which is Src kinase dependent and is enabled 
      by endogenous adenosine acting on A2A receptors. As it is well known, NR2B 
      (Tyr1472) phosphorylation anchors NR2B-containing NMDARs to the surface of 
      post-synaptic membranes, preventing their internalization. This is supported by 
      our electrophysiological experiments showing that co-activation of mGluR5 and 
      NMDARs robustly enhances NMDAR-dependent neuronal excitability recorded in CA1 
      hippocampal region, which temporally coincides with the robust increase in NR2B 
      (Tyr1472) phosphorylation, depends on Src kinases and is also permitted by A2A 
      receptors. Thus, we strongly suggest that NR2B (Tyr1472) phosphorylation 
      constitutes, at least to some extent, the molecular mechanism underlying the 
      mGluR5-mediated enhancement of NMDAR-dependent responses, which is modulated by 
      A2A receptors. A better understanding of the molecular basis of mGluR5/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 A2A 
      receptors license the mGluR5-induced NR2B(Tyr1472) phosphorylation.
CI  - (c) 2015 International Society for Neurochemistry.
FAU - Sarantis, Konstantinos
AU  - Sarantis K
AD  - Physiology Department, Medical School, University of Patras, Patras, Greece.
FAU - Tsiamaki, Eirini
AU  - Tsiamaki E
AD  - Physiology Department, Medical School, University of Patras, Patras, Greece.
FAU - Kouvaros, Stylianos
AU  - Kouvaros S
AD  - Physiology Department, Medical School, University of Patras, Patras, Greece.
FAU - Papatheodoropoulos, Costas
AU  - Papatheodoropoulos C
AD  - Physiology Department, Medical School, University of Patras, Patras, Greece.
FAU - Angelatou, Fevronia
AU  - Angelatou F
AD  - Physiology Department, Medical School, University of Patras, Patras, Greece.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150924
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Excitatory Amino Acid Agents)
RN  - 0 (Grm5 protein, rat)
RN  - 0 (NR2B NMDA receptor)
RN  - 0 (Purinergic Agents)
RN  - 0 (Receptor, Metabotropic Glutamate 5)
RN  - 0 (Receptors, Adenosine A2)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 42HK56048U (Tyrosine)
SB  - IM
MH  - Animals
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Excitatory Amino Acid Agents/pharmacology
MH  - Hippocampus/drug effects/*metabolism
MH  - In Vitro Techniques
MH  - Male
MH  - Patch-Clamp Techniques
MH  - Phosphorylation/drug effects/physiology
MH  - Purinergic Agents/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, Metabotropic Glutamate 5/genetics/*metabolism
MH  - Receptors, Adenosine A2/genetics/*metabolism
MH  - Receptors, N-Methyl-D-Aspartate/genetics/*metabolism
MH  - Statistics, Nonparametric
MH  - Tyrosine/*metabolism
OTO - NOTNLM
OT  - NR2B
OT  - Src kinases
OT  - adenosineA2AR
OT  - hippocampus
OT  - mGluR5
OT  - phosphorylation
EDAT- 2015/08/26 06:00
MHDA- 2016/02/18 06:00
CRDT- 2015/08/26 06:00
PHST- 2015/06/24 00:00 [received]
PHST- 2015/07/23 00:00 [revised]
PHST- 2015/08/07 00:00 [accepted]
PHST- 2015/08/26 06:00 [entrez]
PHST- 2015/08/26 06:00 [pubmed]
PHST- 2016/02/18 06:00 [medline]
AID - 10.1111/jnc.13291 [doi]
PST - ppublish
SO  - J Neurochem. 2015 Nov;135(4):714-26. doi: 10.1111/jnc.13291. Epub 2015 Sep 24.