PMID- 16651266
OWN - NLM
STAT- MEDLINE
DCOM- 20060918
LR  - 20220330
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 281
IP  - 27
DP  - 2006 Jul 7
TI  - Roles of glutamate receptors and the mammalian target of rapamycin (mTOR) 
      signaling pathway in activity-dependent dendritic protein synthesis in 
      hippocampal neurons.
PG  - 18802-15
AB  - Local protein synthesis in neuronal dendrites is critical for synaptic 
      plasticity. However, the signaling cascades that couple synaptic activation to 
      dendritic protein synthesis remain elusive. The purpose of this study is to 
      determine the role of glutamate receptors and the mammalian target of rapamycin 
      (mTOR) signaling in regulating dendritic protein synthesis in live neurons. We 
      first characterized the involvement of various subtypes of glutamate receptors 
      and the mTOR kinase in regulating dendritic synthesis of a green fluorescent 
      protein (GFP) reporter controlled by alphaCaMKII 5' and 3' untranslated regions 
      in cultured hippocampal neurons. Specific antagonists of N-methyl-d-aspartic acid 
      (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and 
      metabotropic glutamate receptors abolished glutamate-induced dendritic GFP 
      synthesis, whereas agonists of NMDA and metabotropic but not AMPA glutamate 
      receptors activated GFP synthesis in dendrites. Inhibitions of the mTOR 
      signaling, as well as its upstream activators, phosphatidylinositol 3-kinase and 
      AKT, blocked NMDA receptor-dependent dendritic GFP synthesis. Conversely, 
      activation of mTOR signaling stimulated dendritic GFP synthesis. In addition, we 
      also found that inhibition of the mTOR kinase blocked dendritic synthesis of the 
      endogenous alphaCaMKII and MAP2 proteins induced by tetanic stimulations in 
      hippocampal slices. These results identify critical roles of NMDA receptors and 
      the mTOR signaling pathway for control of synaptic activity-induced dendritic 
      protein synthesis in hippocampal neurons.
FAU - Gong, Ruomu
AU  - Gong R
AD  - Department of Neurobiology and Behavior, Center for Neurobiology of Learning and 
      Memory, University of California, Irvine, California 92697-3800, USA.
FAU - Park, Chang Sin
AU  - Park CS
FAU - Abbassi, Nima Rezaei
AU  - Abbassi NR
FAU - Tang, Shao-Jun
AU  - Tang SJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20060501
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Receptors, Glutamate)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
SB  - IM
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2
MH  - Calcium-Calmodulin-Dependent Protein Kinases/metabolism
MH  - Cells, Cultured
MH  - Dendrites/*metabolism
MH  - Genes, Reporter
MH  - Green Fluorescent Proteins/biosynthesis/genetics
MH  - Hippocampus/cytology/*metabolism
MH  - Mice
MH  - Neurons/metabolism/ultrastructure
MH  - Protein Kinases/*metabolism
MH  - Receptors, Glutamate/metabolism
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Signal Transduction
MH  - Synapses/metabolism
MH  - TOR Serine-Threonine Kinases
EDAT- 2006/05/03 09:00
MHDA- 2006/09/19 09:00
CRDT- 2006/05/03 09:00
PHST- 2006/05/03 09:00 [pubmed]
PHST- 2006/09/19 09:00 [medline]
PHST- 2006/05/03 09:00 [entrez]
AID - S0021-9258(20)57644-8 [pii]
AID - 10.1074/jbc.M512524200 [doi]
PST - ppublish
SO  - J Biol Chem. 2006 Jul 7;281(27):18802-15. doi: 10.1074/jbc.M512524200. Epub 2006 
      May 1.