S6K1 Phosphorylates and Regulates Fragile X Mental Retardation Protein (FMRP) with the Neuronal Protein Synthesis-dependent Mammalian Target of Rapamycin (mTOR) Signaling Cascade
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Fragile X syndrome is a common form of cognitive deficit caused by the functional absence of fragile X mental retardation protein (FMRP), a dendritic RNA-binding protein that represses translation of specific messages. Although FMRP is phosphorylated in a group I metabotropic glutamate receptor (mGluR) activity-dependent manner following brief protein phosphatase 2A (PP2A)-mediated dephosphorylation, the kinase regulating FMRP function in neuronal protein synthesis is unclear. Here we identify ribosomal protein S6 kinase (S6K1) as a major FMRP kinase in the mouse hippocampus, finding that activity-dependent phosphorylation of FMRP by S6K1 requires signaling inputs from mammalian target of rapamycin (mTOR), ERK1/2, and PP2A. Further, the loss of hippocampal S6K1 and the subsequent absence of phospho-FMRP mimic FMRP loss in the increased expression of SAPAP3, a synapse-associated FMRP target mRNA. Together these data reveal a S6K1-PP2A signaling module regulating FMRP function and place FMRP phosphorylation in the mGluR-triggered signaling cascade required for protein-synthesis-dependent synaptic plasticity.
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Molecular signaling pathways that orchestrate protein synthesis, spine shape, and synaptic plasticity, such as mTOR and ERK, are impaired in fragile X syndrome, possibly because some FMRP target mRNAs encode members of second messenger cascades converging on ERK.
“The molecular signaling pathways orchestrating protein synthesis, spine shape, and synaptic plasticity, such as mTOR and ERK (Figure 2), are also impaired in FXS (72,(87)(88)(89), possibly because some FMRP target mRNAs encode members of second messenger cascades converging on ERK (88,89).”
From Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics (2012) · cites this paper as [72]
Cites
Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling
Inoki, K., Li, Y., Xu, T., & Guan, K.-L. (2003) · Genes & Development · doi:10.1101/gad.1110003 · Cited by 1,911 · see citing works
The mGluR theory of fragile X mental retardation
Bear, M. F., Huber, K. M., & Warren, S. T. (2004) · Trends in Neurosciences · doi:10.1016/j.tins.2004.04.009 · Cited by 1,580 · see citing works
Self-citationRAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1
Burnett, P. E., Barrow, R. K., Cohen, N. A., Snyder, S. H., & Sabatini, D. M. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.4.1432 · Cited by 1,139 · see citing works
Brown, V., Jin, P., Ceman, S., Darnell, J. C., O'Donnell, W. T., Tenenbaum, S. A., Jin, X., Feng, Y., Wilkinson, K. D., Keene, J. D., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00568-2 · Cited by 1,109 · see citing works
Self-citationInvolvement of a calcineurin/ inhibitor-1 phosphatase cascade in hippocampal long-term depression
Mulkey, R. M., Endo, S., Shenolikar, S., & Malenka, R. C. (1994) · Nature · doi:10.1038/369486a0 · Cited by 1,083 · see citing works
Cortico-striatal synaptic defects and OCD-like behaviours in Sapap3-mutant mice
Welch, J. M., Lu, J., Rodriguiz, R. M., Trotta, N. C., Peca, J., Ding, J.-D., Feliciano, C., Chen, M., Adams, J. P., Luo, J., et al. (2007) · Nature · doi:10.1038/nature06104 · Cited by 852 · see citing works
Pende, M., Um, S. H., Mieulet, V., Sticker, M., Goss, V. L., Mestan, J., Mueller, M., Fumagalli, S., Kozma, S. C., & Thomas, G. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.8.3112-3124.2004 · Cited by 743 · see citing works
Self-citationControl of p70 S6 kinase by kinase activity of FRAP in vivo
Brown, E. J., Beal, P. A., Keith, C. T., Chen, J., Shin, T. B., & Schreiber, S. L. (1995) · Nature · doi:10.1038/377441a0 · Cited by 705 · see citing works
Ribosomal S6 Kinase Signaling and the Control of Translation
Dufner, A., & Thomas, G. (1999) · Experimental Cell Research · doi:10.1006/excr.1999.4683 · Cited by 676 · see citing works
Self-citationWeiler, I. J., Irwin, S. A., Klintsova, A. Y., Spencer, C. M., Brazelton, A. D., Miyashiro, K., Comery, T. A., Patel, B., Eberwine, J., & Greenough, W. T. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.10.5395 · Cited by 644 · see citing works
Disruption of the p70s6k/p85s6k gene reveals a small mouse phenotype and a new functional S6 kinase
Shima, H., Pende, M., Chen, Y., Fumagalli, S., THOMAS, G. V., & Kozma, S. C. (1998) · The EMBO Journal · doi:10.1093/emboj/17.22.6649 · Cited by 636 · see citing works
Self-citationHou, L., & Klann, E. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.0995-04.2004 · Cited by 527 · see citing works
Peterson, R., Desai, B. N., Hardwick, J. S., & Schreiber, S. (1999) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.96.8.4438 · Cited by 496 · see citing works
Regulation of NMDA Receptors by an Associated Phosphatase-Kinase Signaling Complex
Westphal, R. S., Tavalin, S. J., Lin, J., Alto, N. M., Fraser, I. D. C., Langeberg, L. K., Sheng, M., & Scott, J. D. (1999) · Science · doi:10.1126/science.285.5424.93 · Cited by 495 · see citing works
A Decade of Molecular Studies of Fragile X Syndrome
O'Donnell, W. T., & Warren, S. T. (2002) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.25.112701.142909 · Cited by 481 · see citing works
Self-citationPhosphorylation of eucaryotic translation initiation factor 4B Ser422 is modulated by S6 kinases
Raught, B., Peiretti, F., Gingras, A., Livingstone, M., Shahbazian, D., Mayeur, G. L., Polakiewicz, R. D., Sonenberg, N., & Hershey, J. W. B. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600193 · Cited by 473 · see citing works
Hypoinsulinaemia, glucose intolerance and diminished β-cell size in S6K1-deficient mice
Pende, M., Kozma, S. C., Jaquet, M., Oorschot, V. M. J., Burcelin, R., MARCHAND‐BRUSTEL, Y. L., Klumperman, J., Thorens, B., & Thomas, G. W. (2000) · Nature · doi:10.1038/35050135 · Cited by 452 · see citing works
Self-citationPearson, R. B., Dennis, P. B., Han, J. W., Williamson, N. A., Kozma, S. C., Wettenhall, R. E., & Thomas, G. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb00212.x · Cited by 443 · see citing works
Self-citationAntar, L. N., Afroz, R., Dictenberg, J. B., Carroll, R. C., & Bassell, G. J. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.0099-04.2004 · Cited by 360 · see citing works
Self-citationSpencer, C. M., Alekseyenko, O., Serysheva, E., Yuva‐Paylor, L. A., & Paylor, R. (2005) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2005.00123.x · Cited by 349 · see citing works
Phosphorylation influences the translation state of FMRP-associated polyribosomes
Ceman, S., O'Donnell, W. T., Reed, M., Patton, S., Pohl, J., & Warren, S. T. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg350 · Cited by 327 · see citing works
Self-citationFilamin is essential in actin cytoskeletal assembly mediated by p21-activated kinase 1
Vadlamudi, R. K., Feng, L., Adam, L., Nguyen, D. N., Ohta, Y., Stossel, T. P., & Kumar, R. (2002) · Nature Cell Biology · doi:10.1038/ncb838 · Cited by 321 · see citing works
Nosyreva, E. D., & Huber, K. M. (2006) · Journal of Neurophysiology · doi:10.1152/jn.01316.2005 · Cited by 292 · see citing works
Nakamoto, M., Nalavadi, V., Epstein, M. P., Narayanan, U., Bassell, G. J., & Warren, S. T. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707484104 · Cited by 245 · see citing works
Self-citationNarayanan, U., Nalavadi, V., Nakamoto, M., Pallas, D. C., Ceman, S., Bassell, G. J., & Warren, S. T. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.2969-07.2007 · Cited by 228 · see citing works
Self-citationWestphal, R. S., Coffee, R. L., Marotta, A., Pelech, S., & Wadzinski, B. E. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.2.687 · Cited by 202 · see citing works
Post-translational protein modification as the substrate for long-lasting memory
Routtenberg, A., & Rekart, J. L. (2004) · Trends in Neurosciences · doi:10.1016/j.tins.2004.11.006 · Cited by 188 · see citing works
Regulation of neuronal PKA signaling through AKAP targeting dynamics
Dell’Acqua, M. L., Smith, K. E., Gorski, J. A., Horne, E. A., Gibson, E. S., & Gomez, L. L. (2006) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2006.01.010 · Cited by 173 · see citing works
Substrate recognition determinants of the mitogen-activated 70K S6 kinase from rat liver.
Flotow, H., & Thomas, G. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)50696-2 · Cited by 158 · see citing works
Self-citationGout, I. T., Minami, T., Hara, K., Tsujishita, Y., Filonenko, V. V., Waterfield, M. D., & Yonezawa, K. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.46.30061 · Cited by 148 · see citing works
Smith, K. E., Gibson, E. S., & Dell’Acqua, M. L. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.3092-05.2006 · Cited by 141 · see citing works
Removal of S6K1 and S6K2 leads to divergent alterations in learning, memory, and synaptic plasticityPreprint
Antion, M. D., Merhav, M., Hoeffer, C. A., Reis, G. F., Kozma, S. C., Thomas, G., Schuman, E. M., Rosenblum, K., & Klann, E. (2008) · Learning & Memory · doi:10.1101/lm.661908 · Cited by 138 · see citing works
Self-citationKanegan, M. J. V., Adams, D. G., Wadzinski, B. E., & Strack, S. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m506986200 · Cited by 132 · see citing works
Phosphorylated tau and the neurodegenerative foldopathies
Kosik, K. S., & Shimura, H. (2004) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2004.10.011 · Cited by 123 · see citing works
Epidermal growth factor-mediated activation of an S6 kinase in Swiss mouse 3T3 cells.
Novak‐Hofer, I., & Thomas, G. (1985) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)39249-9 · Cited by 120 · see citing works
Self-citationRegulation of Global and Specific mRNA Translation by Amino Acids
Kimball, S. R. (2002) · Journal of Nutrition · doi:10.1093/jn/132.5.883 · Cited by 116 · see citing works
Ferrari, S. M., Pearson, R. B., Siegmann, M., Kozma, S. C., & Thomas, G. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)85389-9 · Cited by 113 · see citing works
Self-citationWelch, J. M., Wang, D., & Feng, G. (2004) · The Journal of Comparative Neurology · doi:10.1002/cne.20060 · Cited by 113 · see citing works
Siomi, M. C., Higashijima, K., Ishizuka, A., & Siomi, H. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.24.8438-8447.2002 · Cited by 85 · see citing works
Page, G., Khidir, F. A., Pain, S., Barrier, L., Fauconneau, B., Guillard, O., Piriou, A., & Hugon, J. (2006) · Neurochemistry International · doi:10.1016/j.neuint.2006.01.020 · Cited by 82 · see citing works
Phosphatidylinositol 3 kinase regulates synapse specificity of hippocampal long-term depression
Daw, M. I., Bortolotto, Z. A., Saulle, E., Zaman, S. H., Collingridge, G. L., & Isaac, J. T. R. (2002) · Nature Neuroscience · doi:10.1038/nn903 · Cited by 59 · see citing works
Schalm, S. S., Tee, A. R., & Blenis, J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m413995200 · Cited by 57 · see citing works
Kindler, S., Rehbein, M., Classen, B., Richter, D., & Böckers, T. M. (2004) · Molecular Brain Research · doi:10.1016/j.molbrainres.2004.03.014 · Cited by 56 · see citing works
Cloning and Characterization of p70S6KβDefines a Novel Family of p70 S6 Kinases
Saitoh, M., ten Dijke, P., Miyazono, K., & Ichijo, H. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9784 · Cited by 51 · see citing works
Permeability characteristics of erythrocyte membrane to okadaic acid and calyculin A
Namboodiripad, A. N., & Jennings, M. L. (1996) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1996.270.2.c449 · Cited by 43 · see citing works
Phin, S., Kupferwasser, D., Joseph, L. A. M., & Lee-Fruman, K. K. (2003) · Biochemical Journal · doi:10.1042/bj20021794 · Cited by 26 · see citing works
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Hoeffer, C. A., & Klann, E. (2010) · Trends in Neurosciences · doi:10.1016/j.tins.2009.11.003 · Cited by 1,128 · see citing works
Fragile X Syndrome: Loss of Local mRNA Regulation Alters Synaptic Development and Function
Bassell, G. J., & Warren, S. T. (2008) · Neuron · doi:10.1016/j.neuron.2008.10.004 · Cited by 1,051 · see citing works
Self-citationRegulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks
Magnuson, B., Ekim, B., & Fingar, D. C. (2012) · Biochemical Journal · doi:10.1042/bj20110892 · Cited by 1,015 · see citing works
Translational control of long-lasting synaptic plasticity and memory
Costa-Mattioli, M., Sossin, W. S., Klann, E., & Sonenberg, N. (2009) · Neuron · doi:10.1016/j.neuron.2008.10.055 · Cited by 944 · see citing works
Mutations causing syndromic autism define an axis of synaptic pathophysiology
Auerbach, B. D., Osterweil, E. K., & Bear, M. F. (2011) · Nature · doi:10.1038/nature10658 · Cited by 592 · see citing works
Molecular Mechanisms of Fragile X Syndrome: A Twenty-Year Perspective
Santoro, M. R., Bray, S. M., & Warren, S. T. (2012) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-011811-132457 · Cited by 528 · see citing works
Self-citationJung, H., Yoon, B. C., & Holt, C. E. (2012) · Nature reviews. Neuroscience · doi:10.1038/nrn3210 · Cited by 487 · see citing works
Muddashetty, R. S., Nalavadi, V. C., Gross, C., Yao, X., Xing, L., Laur, O., Warren, S. T., & Bassell, G. J. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.05.006 · Cited by 364 · see citing works
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Besse, F., & Ephrussi, A. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2548 · Cited by 373 · see citing works
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Bhakar, A. L., Dölen, G., & Bear, M. F. (2012) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-060909-153138 · Cited by 370 · see citing works
Making synaptic plasticity and memory last: mechanisms of translational regulationPreprint
Richter, J. D., & Klann, E. (2009) · Genes & Development · doi:10.1101/gad.1735809 · Cited by 345 · see citing works
Tsang, B., Arsenault, J., Vernon, R. M., Lin, H., Sonenberg, N., Wang, L., Bah, A., & Forman-Kay, J. D. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1814385116 · Cited by 328 · see citing works
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Fenton, T. R., & Gout, I. T. (2010) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2010.09.018 · Cited by 338 · see citing works
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Bagni, C., Tassone, F., Neri, G., & Hagerman, R. (2012) · Journal of Clinical Investigation · doi:10.1172/jci63141 · Cited by 321 · see citing works
Bhattacharya, A., Kaphzan, H., Alvarez-Dieppa, A. C., Murphy, J. P., Pierre, P., & Klann, E. (2012) · Neuron · doi:10.1016/j.neuron.2012.07.022 · Cited by 316 · see citing works
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Liu‐Yesucevitz, L., Bassell, G. J., Gitler, A. D., Hart, A. C., Klann, E., Richter, J. D., Warren, S. T., & Wolozin, B. L. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.4105-11.2011 · Cited by 289 · see citing works
Self-citationmTOR: A pathogenic signaling pathway in developmental brain malformations
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Gross, C., Nakamoto, M., Yao, X., Chan, C.-B., Yim, S. Y., Ye, K., Warren, S. T., & Bassell, G. J. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.0402-10.2010 · Cited by 241 · see citing works
Self-citationThe S6K protein family in health and disease
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Winden, K. D., Ebrahimi‐Fakhari, D., & Şahin, M. (2018) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-080317-061747 · Cited by 222 · see citing works
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Pfeiffer, B. E., & Huber, K. M. (2009) · The Neuroscientist · doi:10.1177/1073858409333075 · Cited by 214 · see citing works
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Bateup, H. S., Takasaki, K. T., Saulnier, J. L., Denefrio, C. L., & Sabatini, B. L. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.1617-11.2011 · Cited by 204 · see citing works
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Nelson, D. L., Orr, H. T., & Warren, S. T. (2013) · Neuron · doi:10.1016/j.neuron.2013.02.022 · Cited by 200 · see citing works
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Willemsen, R., Levenga, J., & Oostra, B. (2011) · Clinical Genetics · doi:10.1111/j.1399-0004.2011.01723.x · Cited by 184 · see citing works
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Fernandopulle, M. S., Lippincott-Schwartz, J., & Ward, M. E. (2021) · Nature Neuroscience · doi:10.1038/s41593-020-00785-2 · Cited by 183 · see citing works
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Budimirovic, D. B., & Kaufmann, W. E. (2011) · Developmental Neuroscience · doi:10.1159/000330213 · Cited by 176 · see citing works
Protein translation in synaptic plasticity: mGluR-LTD, Fragile X
Waung, M. W., & Huber, K. M. (2009) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2009.03.011 · Cited by 174 · see citing works
Oostra, B. A., & Willemsen, R. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2009.02.007 · Cited by 161 · see citing works
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Lugo, J. N., Smith, G. D., Arbuckle, E. P., White, J., Holley, A. J., Floruta, C. M., Ahmed, N., Gomez, M. C., & Okonkwo, O. (2014) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2014.00027 · Cited by 159 · see citing works
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Schütt, J., Falley, K., Richter, D., Kreienkamp, H., & Kindler, S. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.042663 · Cited by 155 · see citing works
Niere, F., Wilkerson, J. R., & Huber, K. M. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.4650-11.2012 · Cited by 153 · see citing works
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De Rubeis, S., & Bagni, C. (2010) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2009.09.013 · Cited by 126 · see citing works
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Meyuhas, O., & Dreazen, A. (2009) · Progress in molecular biology and translational science · doi:10.1016/s1877-1173(09)90003-5 · Cited by 125 · see citing works
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Dölen, G., Carpenter, R. L., Ocain, T. D., & Bear, M. F. (2010) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2010.02.008 · Cited by 124 · see citing works
Sasaki, Y., Welshhans, K., Wen, Z., Yao, J., Xu, M. F., Goshima, Y., Zheng, J. Q., & Bassell, G. J. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.0499-10.2010 · Cited by 124 · see citing works
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Sundberg, M., Tochitsky, I., Buchholz, D. E., Winden, K. D., Kujala, V. J., Kapur, K., Cataltepe, D., Turner, D., Han, M., Woolf, C. J., et al. (2018) · Molecular Psychiatry · doi:10.1038/s41380-018-0018-4 · Cited by 120 · see citing works
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Brouwer, J. R., Willemsen, R., & Oostra, B. A. (2008) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30910 · Cited by 113 · see citing works
Banerjee, A., Ifrim, M. F., Valdez‐Sinon, A. N., Raj, N., & Bassell, G. J. (2018) · Brain Research · doi:10.1016/j.brainres.2018.04.008 · Cited by 103 · see citing works
Self-citationTSC1/TSC2 signaling in the CNS
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Therapeutic Strategies in Fragile X Syndrome: From Bench to Bedside and Back
Gross, C., Hoffmann, A., Bassell, G. J., & Berry-Kravis, E. M. (2015) · Neurotherapeutics · doi:10.1007/s13311-015-0355-9 · Cited by 105 · see citing works
Self-citationTargeted treatments for fragile X syndrome
Berry‐Kravis, E., Knox, A. T., & Hervey, C. M. (2011) · Journal of Neurodevelopmental Disorders · doi:10.1007/s11689-011-9074-7 · Cited by 103 · see citing works
Genotype and cognitive phenotype of patients with tuberous sclerosis complex
van Eeghen, A. M., Black, M. E., Pulsifer, M. B., Kwiatkowski, D. J., & Thiele, E. A. (2011) · European Journal of Human Genetics · doi:10.1038/ejhg.2011.241 · Cited by 102 · see citing works
Deregulated mTOR-mediated translation in intellectual disability.
Troca-Marín, J. A., Alves-Sampaio, A., & Montesinos, M. (2012) · Progress in neurobiology · doi:10.1016/j.pneurobio.2012.01.005 · Cited by 97 · see citing works
Chronic administration of AFQ056/Mavoglurant restores social behaviour in Fmr1 knockout mice
Gantois, I., Pop, A. S., de Esch, C. E. F., Buijsen, R. A. M., Pooters, T., Gomez-Mancilla, B., Gasparini, F., Oostra, B. A., D’Hooge, R., & Willemsen, R. (2013) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.10.059 · Cited by 100 · see citing works
Tuberous sclerosis complex, implication from a rare genetic disease to common cancer treatment
Inoki, K., & Guan, K. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp032 · Cited by 98 · see citing works
Frontier of Epilepsy Research - mTOR signaling pathway
Cho, C. (2011) · Experimental & Molecular Medicine · doi:10.3858/emm.2011.43.5.032 · Cited by 92 · see citing works
Beyond controlling cell size: functional analyses of S6K in tumorigenesis
Wu, X., Xie, W., Xie, W.-X., Wei, W.-Y., & Guo, J.-P. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-05081-4 · Cited by 77 · see citing works
Potential therapeutic interventions for fragile X syndrome
Levenga, J., de Vrij, F. M. S., Oostra, B. A., & Willemsen, R. (2010) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2010.08.005 · Cited by 87 · see citing works
Sapap3 Deletion Anomalously Activates Short-Term Endocannabinoid-Mediated Synaptic Plasticity
Chen, M., Wan, Y., Ade, K., Ting, J., Feng, G., & Calakos, N. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.1701-11.2011 · Cited by 82 · see citing works
RNA ‐binding proteins, neural development and the addictions
Bryant, C. D., & Yazdani, N. (2015) · Genes Brain & Behavior · doi:10.1111/gbb.12273 · Cited by 79 · see citing works
mTOR and MAPK: from localized translation control to epilepsy
Pernice, H. F., Schieweck, R., Kiebler, M. A., & Popper, B. (2016) · BMC Neuroscience · doi:10.1186/s12868-016-0308-1 · Cited by 79 · see citing works
Genheden, M., Kenney, J. W., Johnston, H. E., Manousopoulou, A., Garbis, S. D., & Proud, C. G. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.2641-14.2015 · Cited by 78 · see citing works
Sumoylation regulates FMRP-mediated dendritic spine elimination and maturation
Khayachi, A., Gwizdek, C., Poupon, G., Alcor, D., Chafaï, M., Cassé, F., Maurin, T., Prieto, M. C., Folci, A., Graeve, F. D., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03222-y · Cited by 77 · see citing works
Translating nociceptor sensitivity: the role of axonal protein synthesis in nociceptor physiology
Price, T. J., & Géranton, S. M. (2009) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2009.06786.x · Cited by 76 · see citing works
Fragile X mental retardation protein controls ion channel expression and activity
Ferron, L. (2016) · The Journal of Physiology · doi:10.1113/jp270675 · Cited by 76 · see citing works
Regulation of molecular pathways in the Fragile X Syndrome: insights into Autism Spectrum Disorders
De Rubeis, S., & Bagni, C. (2011) · Journal of Neurodevelopmental Disorders · doi:10.1007/s11689-011-9087-2 · Cited by 73 · see citing works
Kanellopoulos, A. K., Σεμελίδου, Ο., Kotini, A. G., Anezaki, M., & Skoulakis, E. M. C. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.1347-12.2012 · Cited by 72 · see citing works
GluN3A: An NMDA Receptor Subunit with Exquisite Properties and Functions
Kehoe, L. A., Bernardinelli, Y., & Müller, D. (2013) · Neural Plasticity · doi:10.1155/2013/145387 · Cited by 70 · see citing works
Castrén, M. L., & Ċastrén, E. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.05.018 · Cited by 68 · see citing works
Verma, V., Paul, A., Vishwanath, A. A., Vaidya, B., & Clement, J. P. (2019) · Open Biology · doi:10.1098/rsob.180265 · Cited by 64 · see citing works
RNA-binding proteins and translational regulation in axons and growth cones
Hörnberg, H., & Holt, C. E. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00081 · Cited by 64 · see citing works
Na, Y., Park, S., Lee, C., Kim, D.-K., Park, J. M., Sockanathan, S., Huganir, R. L., & Worley, P. F. (2016) · Neuron · doi:10.1016/j.neuron.2016.06.017 · Cited by 62 · see citing works
Taha, M. S., Nouri, K., Milroy, L. G., Moll, J. M., Herrmann, C., Brunsveld, L., Piekorz, R. P., & Ahmadian, M. R. (2014) · PLoS ONE · doi:10.1371/journal.pone.0091465 · Cited by 64 · see citing works
Single-molecule imaging of translational output from individual RNA granules in neurons
Tatavarty, V., Ifrim, M. F., Levin, M. K., Korza, G., Barbarese, E., Yu, J. H., & Carson, J. H. (2012) · Molecular Biology of the Cell · doi:10.1091/mbc.e11-07-0622 · Cited by 63 · see citing works
mTOR in health and in sickness
Liko, D., & Hall, M. N. (2015) · Journal of Molecular Medicine · doi:10.1007/s00109-015-1326-7 · Cited by 59 · see citing works
Magdalon, J., Sánchez-Sánchez, S. M., Griesi‐Oliveira, K., & Sertie, A. L. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18030659 · Cited by 58 · see citing works
Autism as early neurodevelopmental disorder: evidence for an sAPPα-mediated anabolic pathway
Lahiri, D. K., Sokol, D. K., Erickson, C. A., Ray, B., Ho, C. Y., & Maloney, B. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00094 · Cited by 59 · see citing works
Iliff, A. J., Renoux, A. J., Krans, A., Usdin, K., Sutton, M. A., & Todd, P. K. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds525 · Cited by 57 · see citing works
Epigenetic regulation in memory and cognitive disorders
Rudenko, A., & Tsai, L. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2012.12.034 · Cited by 56 · see citing works
Wilkerson, J. R., Albanesi, J. P., & Huber, K. M. (2017) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2017.09.035 · Cited by 57 · see citing works
Subregion-specific dendritic spine abnormalities in the hippocampus of Fmr1 KO mice
Levenga, J., de Vrij, F. M. S., Buijsen, R. A. M., Li, T. M. W. Y., Nieuwenhuizen, I. M., Pop, A., Oostra, B. A., & Willemsen, R. (2011) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2011.02.009 · Cited by 55 · see citing works
Regulation of RNA granules by FMRP and implications for neurological diseases
Lai, A., Valdez‐Sinon, A. N., & Bassell, G. J. (2020) · Traffic · doi:10.1111/tra.12733 · Cited by 53 · see citing works
Self-citationWang, H., Kim, S. S., & Zhuo, M. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.116293 · Cited by 52 · see citing works
Dendritic 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 · see citing works
Evolution of the TSC1/TSC2-TOR Signaling Pathway
Serfontein, J., Nisbet, R. E. R., Howe, C. J., & de Vries, P. J. (2010) · Science Signaling · doi:10.1126/scisignal.2000803 · Cited by 52 · see citing works
Coffee, R. L., Williamson, A. J., Adkins, C. M., Gray, M. C., Page, T. L., & Broadie, K. S. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr527 · Cited by 51 · see citing works
Filippini, A., Bonini, D., Lacoux, C., Pacini, L., Zingariello, M., Sancillo, L., Bosisio, D., Salvi, V., Mingardi, J., Via, L. L., et al. (2017) · RNA Biology · doi:10.1080/15476286.2017.1338232 · Cited by 51 · see citing works
A Functional Requirement for PAK1 Binding to the KH(2) Domain of the Fragile X Protein-Related FXR1
Say, E. H. M., Tay, H.-G., Zhao, Z.-S., Baskaran, Y., Li, R., Lim, L., & Manser, E. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.04.004 · Cited by 50 · see citing works
RNA‐binding proteins involved in RNA localization and their implications in neuronal diseases
Tolino, M., Köhrmann, M., & Kiebler, M. (2012) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2012.08160.x · Cited by 42 · see citing works
Kapeli, K., & Yeo, G. W.-M. (2012) · Frontiers in Neuroscience · doi:10.3389/fnins.2012.00144 · Cited by 47 · see citing works
Bernard, P. B., Castano, A. M., O’Leary, H., Simpson, K., Browning, M. D., & Benke, T. A. (2013) · Neurobiology of Disease · doi:10.1016/j.nbd.2013.06.013 · Cited by 48 · see citing works
FUS contributes to mTOR-dependent inhibition of translation
Sévigny, M., Bourdeau‐Julien, I., Venkatasubramani, J. P., Hui, J. B., Dutchak, P. A., & Sephton, C. F. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra120.013801 · Cited by 47 · see citing works
Dendritic protein synthesis in the normal and diseased brain
Swanger, S., & Bassell, G. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.12.003 · Cited by 46 · see citing works
Self-citationPost-Translational Modifications and RNA-Binding Proteins
Lovci, M., Bengtson, M. H., & Massirer, K. B. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-29073-7_12 · Cited by 44 · see citing works
Werner, C. T., Stefanik, M. T., Milovanovic, M., Caccamise, A. J., & Wolf, M. E. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.2412-17.2018 · Cited by 45 · see citing works
hnRNPs Interacting with mRNA Localization Motifs Define AxoNAl RNA Regulons
Lee, S. J., Osés-Prieto, J. A., Kawaguchi, R., Sahoo, P. K., Kar, A. N., Rozenbaum, M., Oliver, D., Chand, S., Ji, H., Shtutman, M. S., et al. (2018) · Molecular & Cellular Proteomics · doi:10.1074/mcp.ra118.000603 · Cited by 44 · see citing works
Trifonova, E. A., Klimenko, A. I., Мустафин, З. С., Lashin, S. A., & Kochetov, A. V. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20246332 · Cited by 43 · see citing works
Chapter 8 Translational Regulatory Mechanisms in Synaptic Plasticity and Memory Storage
Costa‐Mattioli, M., Sonenberg, N., & Richter, J. D. (2009) · Progress in molecular biology and translational science · doi:10.1016/s1877-1173(09)90008-4 · Cited by 43 · see citing works
Autism traits in children and adolescents with Cornelia de Lange syndrome
Srivastava, S., Landy‐Schmitt, C., Clark, B. W., Kline, A. D., Specht, M. W., & Grados, M. A. (2014) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.36573 · Cited by 41 · see citing works
- Authors
- Narayanan, U., Nalavadi, V., Nakamoto, M., Thomas, G., Ceman, S., Bassell, G. J., & Warren, S. T.
- Affiliations
- Emory University (US)
- University of Illinois Urbana-Champaign (US)
- Corresponding author
- Warren, Stephen T.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2008-07
- Volume
- 283
- Issue
- 27
- Pages
- 18478-18482
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC2441545
- OpenAlex
- W2063704147
- Cited by
- 216
- References
- 46
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 2 · 2023: 6 · 2022: 7 · 2021: 5 · 2020: 10 · 2019: 10 · 2018: 13 · 2017: 14 · 2016: 10 · 2015: 11 · 2014: 13 · 2013: 20 · 2012: 23
- FWCI
- 12.57
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship@UMassChan (submittedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS-051127, R01NS051127)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 24064, HD020521, R01HD041591, P30HD024064, HD41591)
- Topics
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- S6K1, FMRP, mTOR signaling, protein synthesis, fragile X syndrome, protein phosphatase 2A, ERK1/2, metabotropic glutamate receptors, hippocampus, synaptic plasticity, RNA-binding proteins, translational regulation
- MeSH terms
- Animals, Cells, Cultured, Fragile X Syndrome, Hippocampus, Humans, Nerve Tissue Proteins, Neuronal Plasticity, Neurons, Phosphorylation, Protein Kinases, RNA, Messenger, Protein Biosynthesis, Signal Transduction, Receptors, Metabotropic Glutamate, Mice, Knockout, Mitogen-Activated Protein Kinase 1, Ribosomal Protein S6 Kinases, 70-kDa, Mitogen-Activated Protein Kinase 3, Mice, Fragile X Mental Retardation Protein, Fragile X Messenger Ribonucleoprotein 1, Protein Phosphatase 2, TOR Serine-Threonine Kinases
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