Roles of glutamate receptors and the mammalian target of rapamycin (mTOR) signaling pathway in activity-dependent dendritic protein synthesis in hippocampal neurons

Ruomu Gong, Sin Park Chang, Nima Rezaei Abbassi, Shao-Jun Tang

Research output: Contribution to journalArticle

178 Citations (Scopus)

Abstract

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 αCaMKII5′ and 3′ untranslated regions in cultured hippocampal neurons. Specific antagonists of N-methyl-D-aspartic acid (NMDA), α-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 αCaMKII 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.

Original languageEnglish
Pages (from-to)18802-18815
Number of pages14
JournalJournal of Biological Chemistry
Volume281
Issue number27
DOIs
StatePublished - Jul 7 2006
Externally publishedYes

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Glutamate Receptors
Sirolimus
Neurons
Green Fluorescent Proteins
N-Methylaspartate
Proteins
Dendrites
Phosphotransferases
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Phosphatidylinositol 3-Kinase
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Metabotropic Glutamate Receptors
Neuronal Plasticity
AMPA Receptors
3' Untranslated Regions
Chemical activation
Glutamic Acid
Acids
Plasticity

ASJC Scopus subject areas

  • Biochemistry

Cite this

Roles of glutamate receptors and the mammalian target of rapamycin (mTOR) signaling pathway in activity-dependent dendritic protein synthesis in hippocampal neurons. / Gong, Ruomu; Chang, Sin Park; Abbassi, Nima Rezaei; Tang, Shao-Jun.

In: Journal of Biological Chemistry, Vol. 281, No. 27, 07.07.2006, p. 18802-18815.

Research output: Contribution to journalArticle

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