HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 27, 18802-18815, July 7, 2006

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 281/27/18802    most recent M512524200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gong, R. Articles by Tang, S.-J. Search for Related Content PubMed PubMed Citation Articles by Gong, R. Articles by Tang, S.-J. Social Bookmarking                      What's this?

Roles of Glutamate Receptors and the Mammalian Target of Rapamycin (mTOR) Signaling Pathway in Activity-dependent Dendritic Protein Synthesis in Hippocampal Neurons^*

From the Department of Neurobiology and Behavior, Center for Neurobiology of Learning and Memory, University of California, Irvine, California 92697-3800

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 byCaMKII 5' and 3' untranslated regions in cultured hippocampal neurons. Specific antagonists of N-methyl-D-aspartic acid (NMDA), -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 CaMKII 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.

Received for publication, November 22, 2005 , and in revised form, April 6, 2006.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1-S6.

¹ To whom correspondence should be addressed: 303 Qureshey Research Laboratory, Center for Neurobiology of Learning and Memory, University of California, Irvine, CA 92697-3800. Tel.: 949-824-9580; Fax: 949-824-9762; E-mail: stang{at}uci.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				H. Jourdi, Y.-T. Hsu, M. Zhou, Q. Qin, X. Bi, and M. Baudry Positive AMPA Receptor Modulation Rapidly Stimulates BDNF Release and Increases Dendritic mRNA Translation J. Neurosci., July 8, 2009; 29(27): 8688 - 8697. [Abstract] [Full Text] [PDF]

				P. S. Buckmaster, E. A. Ingram, and X. Wen Inhibition of the Mammalian Target of Rapamycin Signaling Pathway Suppresses Dentate Granule Cell Axon Sprouting in a Rodent Model of Temporal Lobe Epilepsy J. Neurosci., June 24, 2009; 29(25): 8259 - 8269. [Abstract] [Full Text] [PDF]

				K. Belelovsky, H. Kaphzan, A. Elkobi, and K. Rosenblum Biphasic Activation of the mTOR Pathway in the Gustatory Cortex Is Correlated with and Necessary for Taste Learning J. Neurosci., June 10, 2009; 29(23): 7424 - 7431. [Abstract] [Full Text] [PDF]

				L.-H. Zeng, N. R. Rensing, and M. Wong The Mammalian Target of Rapamycin Signaling Pathway Mediates Epileptogenesis in a Model of Temporal Lobe Epilepsy J. Neurosci., May 27, 2009; 29(21): 6964 - 6972. [Abstract] [Full Text] [PDF]

				R. Bluem, E. Schmidt, C. Corvey, M. Karas, A. Schlicksupp, J. Kirsch, and J. Kuhse Components of the Translational Machinery Are Associated with Juvenile Glycine Receptors and Are Redistributed to the Cytoskeleton upon Aging and Synaptic Activity J. Biol. Chem., December 28, 2007; 282(52): 37783 - 37793. [Abstract] [Full Text] [PDF]

				Y. Huang, B. N. Kang, J. Tian, Y. Liu, H. R. Luo, L. Hester, and S. H. Snyder The Cationic Amino Acid Transporters CAT1 and CAT3 Mediate NMDA Receptor Activation-Dependent Changes in Elaboration of Neuronal Processes via the Mammalian Target of Rapamycin mTOR Pathway J. Neurosci., January 17, 2007; 27(3): 449 - 458. [Abstract] [Full Text] [PDF]