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Roles of Glutamate Receptors and the Mammalian Target of Rapamycin (mTOR) Signaling Pathway in Activity-dependent Dendritic Protein Synthesis in Hippocampal Neurons
Open accessAbstract
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.
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“Activation of mTOR has been functionally linked with local protein synthesis, such as the presynaptically as synapsin I (SYN1), as well as cytoskeletal proteins, such as the activity-regulated cytoskeletal-associated protein (ARC) [15,24,25].”
From The Impact of BDNF, NTRK2, NGFR, CREB1, GSK3B, AKT, MAPK1, MTOR, PTEN, ARC, and SYN1 Genetic Polymorphisms in Antidepressant Treatment Response Phenotypes (2023) · cites this paper as [25]
Citations
Cites
A synaptic model of memory: long-term potentiation in the hippocampus
Bliss, T. V. P., & Collingridge, G. L. (1993) · Nature · doi:10.1038/361031a0 · Cited by 11,566
Upstream and downstream of mTOR
Hay, N., & Sonenberg, N. (2004) · Genes & Development · doi:10.1101/gad.1212704 · Cited by 4,181
The molecular biology of memory storage: a dialogue between genes and synapses
Kandel, E. R. (2001) · Science · doi:10.1126/science.1067020 · Cited by 3,917
Stauffer, S., Gardner, A., Duprez, W., Ungu, D., & Wismer, P. (2019) · Progress in Gene Expression · doi:10.1007/978-1-4684-6811-3 · Cited by 1,969
The molecular basis of CaMKII function in synaptic and behavioural memory
Lisman, J., Schulman, H., & Cline, H. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn753 · Cited by 1,860
Deficient Hippocampal Long-Term Potentiation in α-Calcium-Calmodulin Kinase II Mutant Mice
Silva, A. J., Stevens, C. F., Tonegawa, S., & Wang, Y. (1992) · Science · doi:10.1126/science.1378648 · Cited by 1,472
Phosphatidic Acid-Mediated Mitogenic Activation of mTOR Signaling
Fang, Y., Vilella-Bach, M., Bachmann, R., Flanigan, A., & Chen, J. (2001) · Science · doi:10.1126/science.1066015 · Cited by 1,055
Role for rapid dendritic protein synthesis in hippocampal mGluR-dependent long-term depression.
Huber, K., Kayser, M., & Bear, M. (2000) · Science · doi:10.1126/science.288.5469.1254 · Cited by 1,015
A Requirement for Local Protein Synthesis in Neurotrophin-Induced Hippocampal Synaptic Plasticity
Kang, H., & Schuman, E. M. (1996) · Science · doi:10.1126/science.273.5280.1402 · Cited by 996
Translational Control by MAPK Signaling in Long-Term Synaptic Plasticity and Memory
Kelleher, R. J., Govindarajan, A., Jung, H.-Y., Kang, H., & Tonegawa, S. (2004) · Cell · doi:10.1016/s0092-8674(04)00115-1 · Cited by 845
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Research works printed but not linked: 3
- Miller, 2002, Neuron, 36, 507, 10.1016/S0896-6273(02)00978-9 · DOI
- McCarthy, 2003, Neuroreport, 14, 1357
- Malenka, 2004, Neuron, 44, 5, 10.1016/j.neuron.2004.09.012 · DOI · Paper page
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Traynelis, S. F., Wollmuth, L. P., McBain, C. J., Menniti, F. S., Vance, K. M., Ogden, K. K., Hansen, K. B., Yuan, H., Myers, S. J., & Dingledine, R. (2010) · Pharmacological Reviews · doi:10.1124/pr.109.002451 · Cited by 3,568
“The induction of protein synthesis is, not unexpectedly, dependent upon NMDA receptor activation (Scheetz et al., 2000; Huang et al., 2002b; Gong et al., 2006; Tran et al., 2007).”
BackgroundZeng, L.-H., Rensing, N., & Wong, M. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.0066-09.2009 · Cited by 505
“Because mTOR can be triggered by glutamate receptor stimulation (Lenz and Avruch, 2005; Gong et al., 2006), it is not surprising that the initial widespread mTOR activation occurs with status epilepticus, which causes massive glutamate release.”
BackgroundSynaptic Signaling by All-Trans Retinoic Acid in Homeostatic Synaptic Plasticity
Aoto, J., Nam, C. I., Poon, M. M., Ting, P., & Chen, L. (2008) · Neuron · doi:10.1016/j.neuron.2008.08.012 · Cited by 397
“In addition, dendritic GluR1 and CaMKIIa synthesis induced with a high-K+ protocol (Gong et al., 2006; Ju et al., 2004) was as strong in RARa shRNA-transfected neurons as in control vector (pSuper)-transfected or neighboring untransfected neurons (Figures S8A and S8B).”
BackgroundThe mTOR signaling pathway in the prefrontal cortex is compromised in major depressive disorder
Jernigan, C. S., Goswami, D. B., Austin, M. C., Iyo, A. H., Chandran, A., Stockmeier, C. A., & Karolewicz, B. (2011) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2011.05.010 · Cited by 386
“There is abundant evidence linking mTOR signaling to synaptic plasticity, memory, neurological disorders, and cancer (Gong et al., 2006; Hay and Sonenberg, 2004; Hoeffer and Klann, 2010).”
InfluentialDistinct subclasses of medium spiny neurons differentially regulate striatal motor behaviors
Bateup, H. S., Santini, E., Shen, W., Birnbaum, S. G., Valjent, E., Surmeier, D., Fisone, G., Nestler, E. J., & Greengard, P. (2010) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1009874107 · Cited by 361
“These mice were previously shown to express Cre selectively in striatonigral and striatopallidal neurons, respectively (12).”
BackgroundMethodInfluentialA clustered plasticity model of long-term memory engrams.
Govindarajan, A., Kelleher, R. J., & Tonegawa, S. (2006) · Nature reviews. Neuroscience · doi:10.1038/nrn1937 · Cited by 355
Molecular neurobiology of mTOR
Switon, K., Kotulska, K., Janusz, A., Zmorzyńska, J., & Jaworski, J. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.11.017 · Cited by 405
“The stimulation of NMDARs and mGluRs activates mTOR and increases dendritic protein synthesis (Hou and Klann, 2004; Gong et al., 2006), which contributes to synaptic plasticity (Jaworski and Sheng, 2006; Swiech et al.”
InfluentialRole of mTOR in physiology and pathology of the nervous system
Swiech, L., Perycz, M., Malik, A., & Jaworski, J. (2008) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2007.08.015 · Cited by 338
“Additional proteins regulating synaptic plasticity, such as CamKIIα, PSD95 and Arc were also reported to be expressed in mTORdependent fashion [81,106,107].”
BackgroundSynaptic plasticity in depression: Molecular, cellular and functional correlates
Marsden, W. N. (2012) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2012.12.012 · Cited by 323
mTOR signaling and its roles in normal and abnormal brain development
Takei, N., & Nawa, H. (2014) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2014.00028 · Cited by 317
“BDNF (Takei et al., 2004) and transmitters (Casadio et al., 1999; Carroll et al., 2004; Gong et al., 2006) have been shown to induce “local” activation of mTORC1 and translation (see review in this issue).”
BackgroundArnold, S. E., Lucki, I., Brookshire, B. R., Carlson, G. C., Browne, C. A., Kazi, H., Bang, S., Choi, B., Chen, Y., McMullen, M. F., et al. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.03.011 · Cited by 320
Trimethylamine‐N‐oxide promotes brain aging and cognitive impairment in mice
Li, D., Ke, Y., Zhan, R., Liu, C., Zhao, M., Zeng, A., Shi, X., Ji, L., Cheng, S., Pan, B., et al. (2018) · Aging Cell · doi:10.1111/acel.12768 · Cited by 304
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Querfurth, H., & Lee, H.-K. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00428-5 · Cited by 288
“By supporting protein synthesis in dendrites and their synapses [17], mTOR promotes synaptic plasticity [7, 94] and hippocampal memory consolidation and maintenance [95, 96].”
BackgroundInfluentialSutton, M. A., Taylor, A. M., Ito, H. T., Pham, A., & Schuman, E. M. (2007) · Neuron · doi:10.1016/j.neuron.2007.07.030 · Cited by 274
“…demonstrated, for example, that strong NMDAR stimulation produces several biochemical changes that promote translation initiation (e.g., Banko et al., 2004; Kelleher et al., 2004; Gong et al., 2006), raising the question as to how these changes interact with regulation at the level of elongation.”
BackgroundBuckmaster, P., Ingram, E. A., & Wen, X. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.4179-08.2009 · Cited by 239
“, 2002), where its activation is controlled by a variety of extracellular signals, including glutamate (Cammalleri et al., 2003; Hou and Klann, 2004; Gong et al., 2006) and BDNF (Takei et al.”
BackgroundMinding the calcium store: Ryanodine receptor activation as a convergent mechanism of PCB toxicity
Pessah, I. N., Cherednichenko, G., & Lein, P. J. (2010) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2009.10.009 · Cited by 231
“15); and activity-dependent translation is mediated by the serine-threonine protein kinase mammalian target of rapamycin (mTOR) (Takei et al., 2004; Kumar et al., 2005; Jaworski et al., 2005; Gong et al., 2006).”
BackgroundJourdi, H., Hsu, Y.-T., Zhou, M., Qin, Q., Bi, X., & Baudry, M. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.6078-08.2009 · Cited by 226
“Previous studies have indicated activation of translation by stimulation of metabotropic and NMDA glutamate receptors (Huber at al., 2000; Gong et al., 2006).”
BackgroundRapamycin for treating Tuberous sclerosis and Autism spectrum disorders
Ehninger, D., & Silva, A. J. (2010) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2010.10.002 · Cited by 223
“The TSC proteins are downstream effectors of the PI3K/AKT [105,106] and RAS/MAPK [25,107] pathways that can activate mTORC1 downstream of various neuronal growth factor receptors and neurotransmitter receptors [103,108].”
Glutamate excitotoxicity: Potential therapeutic target for ischemic stroke
Shen, Z., Xiang, M., Chen, C., Ding, F., Wang, Y., Shang, C., Xin, L., Zhang, Y., & Cui, X. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113125 · Cited by 241
Wong, M. (2010) · Epilepsia · doi:10.1111/j.1528-1167.2009.02341.x · Cited by 205
“Given the massive glutamate receptor activation that occurs with kainate status epilepticus, a rationale hypothesis might involve initial stimulation of ionotropic or metabotropic glutamate receptors with subsequent activation of the PI3K/Akt pathway (Sutton & Chandler, 2002; Zhu et al., 2002; Hou & Klann, 2004; Lenz…”
BackgroundFraser, M. M., Bayazitov, I. T., Zakharenko, S. S., & Baker, S. J. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2007.10.048 · Cited by 202
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Boland, B., & Nixon, R. A. (2006) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2006.08.009 · Cited by 163
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Maiese, K. (2015) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12804 · Cited by 202
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Mayer, M. L. (2005) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2005.05.004 · Cited by 3,655
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DeGiosio, R. A., Grubisha, M. J., MacDonald, M. L., McKinney, B. C., Camacho, C. J., & Sweet, R. A. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.974890 · Cited by 173
“This may be mediated by mTOR signaling, as rapamycin blocks tetanusinduced dendritic synthesis of MAP2 protein in hippocampal slice (Gong et al., 2006).”
BackgroundCao, Y., Li, Q., Liu, L., Wu, H., Huang, F., Wang, C., Lan, Y., Zheng, F., Xing, F., Zhou, Q., et al. (2019) · British Journal of Pharmacology · doi:10.1111/bph.14626 · Cited by 167
Carlson, E. S., Stead, J. D. H., Neal, C. R., Petryk, A., & Georgieff, M. K. (2007) · Hippocampus · doi:10.1002/hipo.20307 · Cited by 141
“The latter is the major brain glucose transporter. mTOR pathway molecules can upregulate TfR-1 and regulate translational mechanisms underlying hippocampal plasticity in mammals (Edinger and Thompson, 2002; Gong et al., 2006).”
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BackgroundInfluentialWang, Y., Greenwood, J. S. F., Calcagnotto, M. E., Kirsch, H. E., Barbaro, N. M., & Baraban, S. C. (2007) · Annals of Neurology · doi:10.1002/ana.21058 · Cited by 127
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Tuberous Sclerosis Complex: Neurological, Renal and Pulmonary Manifestations
Franz, D., Bissler, J., & McCormack, F. (2010) · Neuropediatrics · doi:10.1055/s-0030-1269906 · Cited by 138
Everolimus for treatment of tuberous sclerosis complex‐associated neuropsychiatric disorders
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Stamou, M., Streifel, K. M., Goines, P. E., & Lein, P. J. (2013) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2012.12.001 · Cited by 128
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BackgroundGarelick, M. G., & Kennedy, B. K. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2010.08.030 · Cited by 120
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BackgroundRusso, E., Citraro, R., Donato, G., Camastra, C., Iuliano, R., Cuzzocrea, S., Constanti, A., & Sarro, G. D. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.09.019 · Cited by 117
“, 2002), where its activation is controlled by a variety of extracellular stimuli, including glutamate (Cammalleri et al., 2003; Hou and Klann, 2004; Gong et al., 2006) and brain-derived neurotrophic factor (BDNF) (Takei et al.”
Ehninger, D., De Vries, P. J., & Silva, A. J. (2009) · Journal of Intellectual Disability Research · doi:10.1111/j.1365-2788.2009.01208.x · Cited by 120
“2006), possibly mediated by an mTOR-dependent increase in local dendritic synthesis of AMPA receptors (Gong et al. 2006).”
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“There is also evidence that mTOR modulates activitydependent synaptic plasticity in the dendrites of hippocampal neurons (Gong et al., 2006), although the specific role of autophagy was not investigated.”
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“mTORC1 activation can result in translation of additional mRNAs, which have specific roles in synaptic function and plasticity, including NR1, CamKIIalpha, PSD95, Arc, and PKM zeta [18,20,21].”
BackgroundmTOR complex 1: a key player in neuroadaptations induced by drugs of abuse
Neasta, J., Barak, S., Hamida, S. B., & Ron, D. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12725 · Cited by 114
“…signaling Several studies have shown that mTORC1 signaling can be triggered in response to activation of the NMDA receptor (Cammalleri et al. 2003; Gong et al. 2006) whose activity is an important mediator of cocaine and alcohol-dependent behaviors (Wang et al. 2007, 2010a; Stuber et al. 2010).”
BackgroundSantini, E., Huynh, T. N., & Klann, E. (2014) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-420170-5.00005-2 · Cited by 120
Rapamycin reverses status epilepticus-induced memory deficits and dendritic damage
Brewster, A. L., Lugo, J. N., Patil, V. V., Lee, W. L., Qian, Y., Vanegas, F., & Anderson, A. E. (2013) · PLoS ONE · doi:10.1371/journal.pone.0057808 · Cited by 112
Gafford, G. M., Parsons, R. G., & Helmstetter, F. J. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.03.023 · Cited by 110
“Several studies have shown that mTOR signaling is critical for activity-dependent synaptic plasticity in a variety of systems (Casadio et al., 1999; Tang et al., 2002; Gong et al., 2006).”
BackgroundMockett, B. G., Guévremont, D., Wutte, M., Hulme, S. R., Williams, J. M., & Abraham, W. C. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.6656-10.2011 · Cited by 110
“Thus, both translation regulators ERK1/2 and mTOR are phosphorylated after Group I mGluR activation in striatum and cortex (Choe and Wang, 2001a; Gong et al., 2006; Volk et al., 2006; Antion et al., 2008), and CaMKII also activates these regulators (Vanhoutte et al., 1999), although the role of…”
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Chen, S., Atkins, C. M., Liu, C. L., Alonso, O. F., Dietrich, W. D., & Hu, B. R. (2006) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600393 · Cited by 95
“Brief glutamatergic stimulation of cultured neurons activates mTOR to an extent approaching that elicited by brain-derived neurotrophic factor (Gong et al, 2006).”
BackgroundMénard, C., & Quirion, R. (2012) · PLoS ONE · doi:10.1371/journal.pone.0028666 · Cited by 98
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“Interestingly, recent work has shown that neuronal activity triggers rapid mRNA translation via an mTOR-dependent mechanism (Gong et al., 2006; Gelinas et al., 2007; Tsokas et al., 2007; Di Nardo et al.,2007) and that disruption of mTORC1 inhibits late phase longterm potentiation (LTP) in the…”
BackgroundPilar-Cuéllar, F., Vidal, R., Díaz, Á., Castro, E., Dos-Anjos, S., Pascual-Brazo, J., Linge, R., Vargas, V. I., Blanco, H., Martínez‐Villayandre, B., et al. (2013) · Neural Plasticity · doi:10.1155/2013/537265 · Cited by 90
“…synapsin I, or postsynaptically as PSD-95 and GluR1, and cytoskeletal proteins as the activity-regulated cytoskeletal-associated protein (Arc) [27, 241, 243]. mTOR-signaling pathway has been also related to a number of neurological diseases, such as Alzheimer’s disease, Parkinson’s disease, and…”
Oncogenes on my mind: ERK and MTOR signaling in cognitive diseases
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Wang, X., Luo, Y.-X., He, Y.-Y., Li, F.-Q., Shi, H.-S., Xue, L.-F., Xue, Y.-X., & Lu, L. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.1264-10.2010 · Cited by 88
Li, Y., Li, B., Wan, X., Zhang, W., Zhong, L., & Tang, S. (2012) · Molecular Brain · doi:10.1186/1756-6606-5-1 · Cited by 106
“Previous studies have revealed that mTOR signaling is a major molecular pathway in the control of activity-regulated protein synthesis during synaptic plasticity [33-35].”
BackgroundSelf-citationBidinosti, M., Ran, I., Sánchez‐Carbente, M. D. R., Martineau, Y., Gingras, A., Gkogkas, C. G., Raught, B., Bramham, C. R., Sossin, W. S., Costa‐Mattioli, M., et al. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.02.022 · Cited by 100
“Translational expression from this reporter has been shown to be induced by activity and is normally weak in dendrites distal to the cell body in unstimulated conditions (Aakalu et al., 2001; Gong et al., 2006).”
Mazucanti, C. H., Cabral‐Costa, J. V., Vasconcelos, A. R., Andreotti, D. Z., Scavone, C., & Kawamoto, E. M. (2015) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026615666150610125715 · Cited by 103
“This last action is, at least partly, achieved by regulating the synthesis of the N-MethylD-Aspartate (NMDA) receptor subunit 1 (NR1) [33], calcium calmodulin-dependent kinase II α (CaMKIIα) [34] and postsynaptic density-95 (PSD-95) [35].”
BackgroundMacromolecular synthesis, distributed synaptic plasticity, and fear conditioning
Helmstetter, F. J., Parsons, R. G., & Gafford, G. M. (2007) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2007.09.002 · Cited by 91
“control the synthesis of locally translated proteins at active synapses (Cammalleri, et al., 2003; Gong et al., 2006; Tang, et al., 2002).”
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“Cyclin-dependent kinase 5, a proline-directed serine/threonine kinase can also phosphorylate the Homer binding domain of both mGluR1 and mGluR5, enhancing the interaction (Orlando et al., 2009).”
BackgroundAmidfar, M., Woelfer, M., Réus, G. Z., Quevedo, J., Walter, M., & Kim, Y. (2019) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2019.109668 · Cited by 95
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Self-citationChong, Z. Z., Li, F.-Q., & Maiese, K. (2007) · International Journal of Molecular Medicine · doi:10.3892/ijmm.19.2.263 · Cited by 85
Consolidation and translation regulation: Figure 1.Preprint
Gal-Ben-Ari, S., Kenney, J. W., Ounalla-Saad, H., Taha, E., David, O., Levitan, D., Gildish, I., Panja, D., Pai, B., Wibrand, K., et al. (2012) · Learning & Memory · doi:10.1101/lm.026849.112 · Cited by 80
“Distinct types of glutamate receptors, such as NMDAR, AMPAR, and mGluRs are required for activation of mTOR/S6K signaling and CaMK__a synthesis in hippocampal dendrites following LTP (Cammalleri et al. 2003; Gong et al. 2006).”
BackgroundIs the mTOR‐signalling cascade disrupted in Schizophrenia?
Gururajan, A., & van den Buuse, M. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12622 · Cited by 81
“Gong et al. (2006), in their experiments with mouse embryonic neurons, showed that rapamycin inhibited hippo-”
BackgroundWNT5A Signaling Contributes to Aβ-Induced Neuroinflammation and Neurotoxicity
Li, B., Zhong, L., Yang, X., Andersson, T., Huang, M., & Tang, S.-J. (2011) · PLoS ONE · doi:10.1371/journal.pone.0022920 · Cited by 81
“C57BL E18 cortical cultures were prepared, as described”
MethodSelf-citationAhmad, F., Singh, K. P., Das, D., Gowaikar, R., Shaw, E., Ramachandran, A., Rupanagudi, K. V., Kommaddi, R. P., Bennett, D. A., & Ravindranath, V. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2016.6860 · Cited by 99
“Akt1-mTOR signaling is a key component of activitydependent local dendritic protein translation (15, 44, 48).”
Therapeutic role of mammalian target of rapamycin (mTOR) inhibition in preventing epileptogenesis
McDaniel, S. S., & Wong, M. (2011) · Neuroscience Letters · doi:10.1016/j.neulet.2011.02.037 · Cited by 78
“Since putative learning mechanisms, such as long term potentiation and long term depression, rely on protein synthesis for sustained changes in synaptic strength, it is not surprising that they require mTOR activity [40, 50, 102].”
BackgroundTaking aim at Alzheimer's disease through the mammalian target of rapamycin
Maiese, K. (2014) · Annals of Medicine · doi:10.3109/07853890.2014.941921 · Cited by 88
Driving neural regeneration through the mammalian target of rapamycin
Maiese, K. (2014) · Neural Regeneration Research · doi:10.4103/1673-5374.139453 · Cited by 80
“Dendritic protein synthesis in hippocampal neurons is promoted through mTOR activity (Gong et al., 2006).”
BackgroundControl of Synaptic Plasticity and Memory via Suppression of Poly(A)-Binding Protein
Khoutorsky, A., Yanagiya, A., Gkogkas, C. G., Fabian, M. R., Prager‐Khoutorsky, M., Cao, R., Gamache, K., Bouthiette, F., Parsyan, A. E., Sorge, R. E., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.02.025 · Cited by 72
“The procedures for fluorescent immunostaining and data analysis were previously described (Gong et al., 2006).”
InfluentialBell, J. J. L., Rakhade, S. N., Klein, P., Obeid, M., Jackson, M. C., Joseph, A., & Jensen, F. E. (2013) · Epilepsia · doi:10.1111/epi.12378 · Cited by 79
“…these studies suggest that glutamate receptor activation may interact with the mTOR pathway, with other studies suggesting transcriptional and translational changes at the synapse that could mediate the molecular mechanics of these changes (Gong et al., 2006; Talos et al., 2012; Sun et al., 2013).”
BackgroundEhninger, D. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.05.015 · Cited by 68
Retrograde Changes in Presynaptic Function Driven by Dendritic mTORC1
Henry, F. E., McCartney, A. J., Neely, R., Perez, A. S., Carruthers, C. J. L., Stuenkel, E. L., Inoki, K., & Sutton, M. A. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.2149-12.2012 · Cited by 69
“…an important control point for protein synthesis related to synaptic plasticity (Casadio et al., 1999; Tang et al., 2002; Cammalleri et al., 2003; Gong et al., 2006) and memory (Tischmeyer et al., 2003; Dash et al., 2006; Blundell et al., 2008). mTOR is a serine/threonine protein kinase that…”
BackgroundCurrent Management of Tuberous Sclerosis Complex
Krueger, D., & Franz, D. (2008) · Paediatric drugs · doi:10.2165/00148581-200810050-00004 · Cited by 68
Callum, P. M., Hebert, M. A., Adamec, R. E., & Blundell, J. J. (2013) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2013.08.014 · Cited by 68
Wan, X.-Z., Li, B., Li, Y.-C., Yang, X., Zhang, W., Zhong, L., & Tang, S.-J. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.3916-11.2012 · Cited by 66
“This discrepancy is probably due to NMDAstimulated rapid translation from pre-existing mRNA, as suggested by previous studies (Ouyang et al., 1999; Gong et al., 2006; Li et al., 2012).”
ResultSelf-citationHuang, Y., Kang, B. N., Tian, J., Liu‐Chittenden, Y., Luo, H. R., Hester, L. D., & Snyder, S. H. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.4489-06.2007 · Cited by 57
“Neuronal activity regulates the mTOR pathway (Lenz and Avruch, 2005; Gong et al., 2006; Raab-Graham et al., 2006), but molecular mechanisms for these influences have not been readily evident.”
Downregulated AKT-mTOR signaling pathway proteins in dorsolateral prefrontal cortex in Schizophrenia
Chadha, R., & Meador‐Woodruff, J. H. (2020) · Neuropsychopharmacology · doi:10.1038/s41386-020-0614-2 · Cited by 74
Belelovsky, K., Kaphzan, H., Elkobi, A., & Rosenblum, K. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.3809-08.2009 · Cited by 62
“, 2007), and specifically a critical role in control of synaptic activity-induced protein synthesis (such as -CaMKII and MAP2) in hippocampal neurons (Gong et al., 2006).”
BackgroundWang, H., Huang, B., Wang, W., Li, J., Chen, Y., Flynn, T., Zhao, M., Zhou, Z., Lin, X., Zhang, Y., et al. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.09.049 · Cited by 67
Giannotti, G., Caffino, L., Calabrese, F., Racagni, G., Riva, M., & Fumagalli, F. (2014) · International Journal of Neuropsychopharmacology · doi:10.1017/s1461145713001454 · Cited by 61
“…enhancement, in turn, resulted in a selective activation of the Akt-dependent pathway that subsequently activated both mTOR and S6 phosphorylation (Gong et al., 2006), a canonical pathway known to be activated by (a) 150 * * * *** * * Homogenate Crude synaptosomal fraction tr kB p ro te in le…”
BackgroundYang, L., Zhang, J., Zheng, K., Shen, H., & Chen, X. (2013) · The Journals of Gerontology Series A · doi:10.1093/gerona/glt091 · Cited by 62
Zhang, W., Shi, Y., Peng, Y., Zhong, L., Zhu, S., Zhang, W., & Tang, S.-J. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.002840 · Cited by 59
“Primary cultures of cortical neurons were prepared from C57BL/6 mouse embryos (E16) as previously described (40, 41).”
MethodSelf-citationYu, J.-J., Zhang, Y., Wang, Y., Wen, Z.-Y., Liu, X., Qin, J., & Yang, J.-L. (2012) · Psychopharmacology · doi:10.1007/s00213-012-2823-9 · Cited by 66
“…is a member of serine/threonine protein kinase and plays an essential role in cell growth and survival through its regulation on initiation of translation (Guertin and Sabatini 2005). mTOR function is regulated by the activation of glutamate N-methyl-D-aspartate (NMDA) receptors (Gong et al. 2006).”
Therapeutic Promise and Principles: Metabotropic Glutamate Receptors
Maiese, K., Chong, Z. Z., Shang, Y., & Hou, J. (2008) · Oxidative Medicine and Cellular Longevity · doi:10.4161/oxim.1.1.6842 · Cited by 79
Zeng, Y.-Q., Zhang, J., Zhu, Y.-G., Zhang, J., Shen, H., Lu, J.-P., Pan, X.-D., Lin, N., Dai, X.-M., Zhou, M., et al. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13056 · Cited by 55
“mTOR can directly act at synapses to promote synthesis of proteins necessary to facilitate plasticity, including NR1, CaMKIIa, PSD-95, Arc, and protein kinase C isoform protein kinase M zeta (Lee et al. 2005; Gong et al. 2006; Kelly et al. 2007; Garelick and Kennedy 2011).”
BackgroundmTORC1-dependent protein synthesis underlying rapid antidepressant effect requires GABABR signaling.
Workman, E. R., Niere, F., & Raab-Graham, K. F. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.05.037 · Cited by 55
“Because activation of mTOR kinase is generally regarded as a consequence of NMDAR stimulation, it is unknown how NMDAR antagonists increase active mTOR (Gong et al., 2006; Raab-Graham et al., 2006).”
BackgroundDendritic mRNA Targeting and Translation
Kindler, S., & Kreienkamp, H. (2012) · Advances in experimental medicine and biology · doi:10.1007/978-3-7091-0932-8_13 · Cited by 54
Wang, L., Budolfson, K., & Wang, F. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2010.10.035 · Cited by 51
“Since mTOR plays important roles in regulating dendritic protein synthesis, synapse formation, synaptic plasticity, and learning and memory (Cammalleri et al., 2003; Kelleher et al., 2004; Takei et al., 2004; Gong et al., 2006; Parsons et al., 2006; Slipczuk et al., 2009), the observed loss of dendritic spines could p…”
BackgroundWang, H., Kim, S. S., & Zhuo, M. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.116293 · Cited by 52
Kandratavicius, L., Rosa-Neto, P., Monteiro, M. R., Guiot, M., Assirati, J. A., Carlotti, C., Kobayashi, E., & Leite, J. P. (2013) · Hippocampus · doi:10.1002/hipo.22160 · Cited by 52
“Dendrite protein synthesis is particularly dependent on group I mGluRs activation in the hippocampus (Gong et al., 2006).”
BackgroundWu, J., McCallum, S. E., Glick, S. D., & Huang, Y. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.10.041 · Cited by 52
Jahrling, J. B., & Laberge, R.-M. (2015) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026615666150610125856 · Cited by 55
“Furthermore, mTOR activity has been noted to promote the synthesis of dendritic proteins within hippocampal neurons [45].”
BackgroundVargas-Martínez, F., Uvnäs-Moberg, K., Petersson, M., Olausson, H. A., & Jiménez-Estrada, I. (2014) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2014.10.001 · Cited by 51
Fragile x mental retardation (Fmr-1) gene expression is down regulated in brain of mice during aging
Singh, K., Gaur, P., & Prasad, S. (2007) · Molecular Biology Reports · doi:10.1007/s11033-006-9032-8 · Cited by 49
Oh, J., Kim, Y.-K., Kim, S., Lee, B., Jang, J., Kwon, S., & Park, H. (2018) · Scientific Reports · doi:10.1038/s41598-018-30337-5 · Cited by 52
Striking a balance: PIP2 and PIP3 signaling in neuronal health and disease
Tariq, K., & Luikart, B. W. (2021) · Exploration of Neuroprotective Therapy · doi:10.37349/ent.2021.00008 · Cited by 57
“The stimulation of mTOR increases dendritic protein synthesis locally and contributes to synaptic and structural plasticity [150, 151].”
BackgroundShang, N., Zhang, P., Wang, S., Chen, J.-P., Fan, R., Chen, J., Huang, T., Wang, Y.-H., Duncan, J. W., Zhang, L., et al. (2020) · Neurotoxicity research · doi:10.1007/s12640-020-00230-z · Cited by 47
“…of mTOR) (Blundell et al. 2008; Parsons et al. 2006). mTOR is an important neuronal regulatory protein, capable of phosphorylating multiple downstream target proteins to inhibit cell death processes associated with cognitive impairment (Goncalves et al. 2017; Gong et al. 2006; Zare et al. 2013).”
BackgroundDendritic protein synthesis in the normal and diseased brain
Swanger, S. A., & Bassell, G. J. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.12.003 · Cited by 51
“studies showed that activation of NMDA, mGlu1/5, and estrogen receptors also induce local GFP synthesis using 30 UTR reporters (Gong et al., 2006; Sarkar et al., 2010).”
BackgroundMethodInfluentialMedalla, M., Chang, W., Calderazzo, S. M., Go, V., Tsolias, A., Goodliffe, J. W., Pathak, D., de Alba, D., Pessina, M. A., Rosene, D. L., et al. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.2226-19.2020 · Cited by 51
“In rodents, mTOR activation in vivo promotes hyperexcitability, axonal sprouting, and synthesis of MAP2 in dendrites (Gong et al., 2006; Park et al., 2008; Lee et al., 2014), whereas mTOR inhibition can increase dendritic K1 and NMDA channel expression (Raab-Graham et al., 2006).”
Background
Metadata
- Authors
- Gong, R., Park, C. S., Abbassi, N. R., & Tang, S.-J.
- Affiliations
- University of California, Irvine (US)
- Corresponding author
- Tang, Shao-Jun
- ORCID
- Tang, Shao-Jun
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2006-07
- Volume
- 281
- Issue
- 27
- Pages
- 18802-18815
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2064438779
- Cited by
- 249
- References
- 73
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 6 · 2023: 6 · 2022: 11 · 2021: 14 · 2020: 11 · 2019: 7 · 2018: 13 · 2017: 14 · 2016: 10 · 2015: 21 · 2014: 14 · 2013: 19 · 2012: 25
- FWCI
- 6.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- dendritic protein synthesis, glutamate receptors, mTOR signaling, NMDA receptor, AMPA receptors, metabotropic glutamate receptors, hippocampal neurons, synaptic plasticity, CaMKIIα, MAP2, phosphatidylinositol 3-kinase, Akt, tetanic stimulation, local translation
- MeSH terms
- Animals, Cells, Cultured, Dendrites, Hippocampus, Neurons, Protein Kinases, Synapses, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Receptors, Glutamate, Calcium-Calmodulin-Dependent Protein Kinases, Genes, Reporter, Green Fluorescent Proteins, Mice, Calcium-Calmodulin-Dependent Protein Kinase Type 2, TOR Serine-Threonine Kinases
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