PMID- 18316404
OWN - NLM
STAT- MEDLINE
DCOM- 20080619
LR  - 20220309
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 28
IP  - 9
DP  - 2008 May
TI  - mGluR-dependent long-term depression is associated with increased phosphorylation 
      of S6 and synthesis of elongation factor 1A but remains expressed in 
      S6K-deficient mice.
PG  - 2996-3007
LID - 10.1128/MCB.00201-08 [doi]
AB  - Metabotropic glutamate receptor-dependent long-term depression (mGluR-LTD) in the 
      hippocampus requires rapid protein synthesis, which suggests that mGluR 
      activation is coupled to signaling pathways that regulate translation. Herein, we 
      have investigated the signaling pathways that couple group I mGluRs to ribosomal 
      S6 protein phosphorylation and 5'oligopyrimidine tract (5'TOP)-encoded protein 
      synthesis during mGluR-LTD. We found that mGluR-LTD was associated with increased 
      phosphorylation of p70S6 kinase (S6K1) and S6, as well as the synthesis of the 
      5'TOP-encoded protein elongation factor 1A (EF1A). Moreover, we found that 
      LTD-associated increases in S6K1 phosphorylation, S6 phosphorylation, and levels 
      of EF1A were sensitive to inhibitors of phosphoinositide 3-kinase (PI3K), 
      mammalian target of rapamycin (mTOR), and extracellular signal-regulated kinase 
      (ERK). However, mGluR-LTD was normal in S6K1 knockout mice and enhanced in both 
      S6K2 knockout mice and S6K1/S6K2 double knockout mice. In addition, we observed 
      that LTD-associated increases in S6 phosphorylation were still increased in S6K1- 
      and S6K2-deficient mice, whereas basal levels of EF1A were abnormally elevated. 
      Taken together, these findings indicate that mGluR-LTD is associated with PI3K-, 
      mTOR-, and ERK-dependent alterations in the phosphorylation of S6 and S6K. Our 
      data also suggest that S6Ks are not required for the expression of mGluR-LTD and 
      that the synthesis of 5'TOP-encoded proteins is independent of S6Ks during 
      mGluR-LTD.
FAU - Antion, Marcia D
AU  - Antion MD
AD  - Center for Neural Science, New York University, 4 Washington Place, Room 809, New 
      York, NY 10003, USA.
FAU - Hou, Lingfei
AU  - Hou L
FAU - Wong, Helen
AU  - Wong H
FAU - Hoeffer, Charles A
AU  - Hoeffer CA
FAU - Klann, Eric
AU  - Klann E
LA  - eng
GR  - R01 NS034007/NS/NINDS NIH HHS/United States
GR  - R01 NS047384/NS/NINDS NIH HHS/United States
GR  - NS047384/NS/NINDS NIH HHS/United States
GR  - R37 NS034007/NS/NINDS NIH HHS/United States
GR  - R29 NS034007/NS/NINDS NIH HHS/United States
GR  - NS034007/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080303
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Peptide Elongation Factor 1)
RN  - 0 (Receptors, Metabotropic Glutamate)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Animals
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Hippocampus/physiology
MH  - In Vitro Techniques
MH  - *Long-Term Synaptic Depression
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Peptide Elongation Factor 1/*biosynthesis
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphorylation
MH  - Protein Kinases/metabolism
MH  - RNA 5' Terminal Oligopyrimidine Sequence
MH  - Receptors, Metabotropic Glutamate/*physiology
MH  - Ribosomal Protein S6 Kinases/genetics/*metabolism
MH  - Ribosomal Protein S6 Kinases, 70-kDa/genetics/metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases
PMC - PMC2293080
EDAT- 2008/03/05 09:00
MHDA- 2008/06/20 09:00
PMCR- 2008/09/01
CRDT- 2008/03/05 09:00
PHST- 2008/03/05 09:00 [pubmed]
PHST- 2008/06/20 09:00 [medline]
PHST- 2008/03/05 09:00 [entrez]
PHST- 2008/09/01 00:00 [pmc-release]
AID - MCB.00201-08 [pii]
AID - 0201-08 [pii]
AID - 10.1128/MCB.00201-08 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2008 May;28(9):2996-3007. doi: 10.1128/MCB.00201-08. Epub 2008 Mar 
      3.