PMID- 27231330
OWN - NLM
STAT- MEDLINE
DCOM- 20170501
LR  - 20211204
IS  - 1521-0111 (Electronic)
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 90
IP  - 2
DP  - 2016 Aug
TI  - Glutamate Delta-1 Receptor Regulates Metabotropic Glutamate Receptor 5 Signaling 
      in the Hippocampus.
PG  - 96-105
LID - 10.1124/mol.116.104786 [doi]
AB  - The delta family of ionotropic glutamate receptors consists of glutamate delta-1 
      (GluD1) and glutamate delta-2 receptors. We have previously shown that GluD1 
      knockout mice exhibit features of developmental delay, including impaired spine 
      pruning and switch in the N-methyl-D-aspartate receptor subunit, which are 
      relevant to autism and other neurodevelopmental disorders. Here, we identified a 
      novel role of GluD1 in regulating metabotropic glutamate receptor 5 (mGlu5) 
      signaling in the hippocampus. Immunohistochemical analysis demonstrated 
      colocalization of mGlu5 with GluD1 punctas in the hippocampus. Additionally, 
      GluD1 protein coimmunoprecipitated with mGlu5 in the hippocampal membrane 
      fraction, as well as when overexpressed in human embryonic kidney 293 cells, 
      demonstrating that GluD1 and mGlu5 may cooperate in a signaling complex. The 
      interaction of mGlu5 with scaffold protein effector Homer, which regulates 
      mechanistic target of rapamycin (mTOR) signaling, was abnormal both under basal 
      conditions and in response to mGlu1/5 agonist (RS)-3,5-dihydroxyphenylglycine 
      (DHPG) in GluD1 knockout mice. The basal levels of phosphorylated mTOR and 
      protein kinase B, the signaling proteins downstream of mGlu5 activation, were 
      higher in GluD1 knockout mice, and no further increase was induced by DHPG. We 
      also observed higher basal protein translation and an absence of DHPG-induced 
      increase in GluD1 knockout mice. In accordance with a role of mGlu5-mediated mTOR 
      signaling in synaptic plasticity, DHPG-induced internalization of surface 
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunits was 
      impaired in the GluD1 knockout mice. These results demonstrate that GluD1 
      interacts with mGlu5, and loss of GluD1 impairs normal mGlu5 signaling 
      potentially by dysregulating coupling to its effector. These studies identify a 
      novel role of the enigmatic GluD1 subunit in hippocampal function.
CI  - Copyright (c) 2016 by The American Society for Pharmacology and Experimental 
      Therapeutics.
FAU - Suryavanshi, Pratyush S
AU  - Suryavanshi PS
AD  - Department of Pharmacology, Creighton University, Omaha, Nebraska.
FAU - Gupta, Subhash C
AU  - Gupta SC
AD  - Department of Pharmacology, Creighton University, Omaha, Nebraska.
FAU - Yadav, Roopali
AU  - Yadav R
AD  - Department of Pharmacology, Creighton University, Omaha, Nebraska.
FAU - Kesherwani, Varun
AU  - Kesherwani V
AD  - Department of Pharmacology, Creighton University, Omaha, Nebraska.
FAU - Liu, Jinxu
AU  - Liu J
AD  - Department of Pharmacology, Creighton University, Omaha, Nebraska.
FAU - Dravid, Shashank M
AU  - Dravid SM
AD  - Department of Pharmacology, Creighton University, Omaha, Nebraska 
      ShashankDravid@creighton.edu.
LA  - eng
GR  - R21 MH098270/MH/NIMH NIH HHS/United States
PT  - Journal Article
DEP - 20160526
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (Protein Isoforms)
RN  - 0 (Receptor, Metabotropic Glutamate 5)
RN  - 0 (Receptors, Glutamate)
RN  - 0 (Receptors, Metabotropic Glutamate)
RN  - 0 (glutamate receptor delta 1)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Gene Deletion
MH  - Hippocampus/*metabolism
MH  - Immunoprecipitation
MH  - Mice, Knockout
MH  - Models, Biological
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein Isoforms/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Receptor, Metabotropic Glutamate 5/*metabolism
MH  - Receptors, Glutamate/*metabolism
MH  - Receptors, Metabotropic Glutamate/metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC4959088
EDAT- 2016/05/28 06:00
MHDA- 2017/05/02 06:00
PMCR- 2017/08/01
CRDT- 2016/05/28 06:00
PHST- 2016/04/19 00:00 [received]
PHST- 2016/05/24 00:00 [accepted]
PHST- 2016/05/28 06:00 [entrez]
PHST- 2016/05/28 06:00 [pubmed]
PHST- 2017/05/02 06:00 [medline]
PHST- 2017/08/01 00:00 [pmc-release]
AID - mol.116.104786 [pii]
AID - MOL_104786 [pii]
AID - 10.1124/mol.116.104786 [doi]
PST - ppublish
SO  - Mol Pharmacol. 2016 Aug;90(2):96-105. doi: 10.1124/mol.116.104786. Epub 2016 May 
      26.