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Fragile X mental retardation protein is translated near synapses in response to neurotransmitter activation
Open accessAbstract
Local translation of proteins in distal dendrites is thought to support synaptic structural plasticity. We have previously shown that metabotropic glutamate receptor (mGluR1) stimulation initiates a phosphorylation cascade, triggering rapid association of some mRNAs with translation machinery near synapses, and leading to protein synthesis. To determine the identity of these mRNAs, a cDNA library produced from distal nerve processes was used to screen synaptic polyribosome-associated mRNA. We identified mRNA for the fragile X mental retardation protein (FMRP) in these processes by use of synaptic subcellular fractions, termed synaptoneurosomes. We found that this mRNA associates with translational complexes in synaptoneurosomes within 1-2 min after mGluR1 stimulation of this preparation, and we observed increased expression of FMRP after mGluR1 stimulation. In addition, we found that FMRP is associated with polyribosomal complexes in these fractions. In vivo, we observed FMRP immunoreactivity in spines, dendrites, and somata of the developing rat brain, but not in nuclei or axons. We suggest that rapid production of FMRP near synapses in response to activation may be important for normal maturation of synaptic connections.
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“In fact, in both assays there was more FMRP immunoprecipitated from the DHPG-treated WT SNs, which is in agreement with previous reports that DHPG stimulates the dendritic translation of FMRP [22,39].”
From FMRP Mediates mGluR5-Dependent Translation of Amyloid Precursor Protein (2007) · cites this paper as [39]
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“In synapto-somal preparations, stimulation of mGluR results in a FMRP-dependent increase in protein synthesis (Weiler et al., 1997, 2004).”
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D’Antoni, S., Spatuzza, M., Bonaccorso, C. M., Musumeci, S. A., Ciranna, L., Nicoletti, F., Huber, K. M., & Catania, M. V. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.02.003 · Cited by 97
“FXS was first linked to group-I mGlu receptors when FMRP was shown to be rapidly synthesized in synaptoneurosomes in response to group-I mGlu agonists (Weiler et al., 1997).”
BackgroundPop, A. S., Gomez‐Mancilla, B., Neri, G., Willemsen, R., & Gasparini, F. (2013) · Psychopharmacology · doi:10.1007/s00213-013-3330-3 · Cited by 101
“(1997) who observed that activation of group I mGluRs with 3,5-dihydroxyphenylglycine stimulated protein synthesis in synaptoneurosomes including the expression of FMRP (Weiler et al. 1997).”
BackgroundMelatonin profiles and sleep characteristics in boys with fragile X syndrome: A preliminary study
Gould, E. L., Loesch, D. Z., Martin, M. J., Hagerman, R. J., Armstrong, S. M., & Huggins, R. (2000) · American Journal of Medical Genetics · doi:10.1002/1096-8628(20001211)95:4 · Cited by 101
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“sion was dependent on protein synthesis (21,22).”
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“The stimulation of group 1 mGluR with the specific agonist DHPG normally induces FMR protein translation in dendrites (Weiler et al., 1997).”
BackgroundIncreased rates of cerebral glucose metabolism in a mouse model of fragile X mental retardation
Qin, M., Kang, J. Y., & Smith, C. B. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.242377399 · Cited by 93
Steward, O., & Halpain, S. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-18-07834.1999 · Cited by 99
“Interestingly, an mRNA with sequence homology to fragile X mental retardation protein was among the mRNAs that were regulated in this fashion (Weiler et al., 1997).”
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The Fragile X mental retardation protein
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Update on the implication of potassium channels in autism: K+ channelautism spectrum disorder
Guglielmi, L. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00034 · Cited by 89
“In particular, FRMP appears to play a critical role in the maintenance of LTD and LTP in the hippocampus (Weiler et al., 1997; Huber et al., 2000, 2002; Hou et al., 2006; Lauterborn et al., 2007; Michalon et al., 2012).”
BackgroundQiu, X., Xiao, X., Li, N., & Li, Y. (2016) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2016.09.002 · Cited by 90
“FMR1 gene plays an important role in synaptic plasticity and neuronal maturation through its regulation of mRNA transport to neuronal dendrites (Weiler and Greenough, 1997).”
BackgroundFragile X Syndrome: From Molecular Aspect to Clinical Treatment
Protic, D. D., Aishworiya, R., Salcedo‐Arellano, M. J., Tang, S. J., Milisavljevic, J., Mitrovic, F., Hagerman, R. J., & Budimirovic, D. B. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23041935 · Cited by 103
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Tranfaglia, M. R. (2011) · Developmental Neuroscience · doi:10.1159/000329421 · Cited by 97
“The seminal finding that FMRP is translated in response to synaptic activity [Weiler et al., 1997], mediated by metabotropic glutamate receptors, shifted research efforts to understanding the role of glutamatergic neurotransmission.”
BackgroundTiedge, H., Bloom, F. E., & Richter, D. (1999) · Science · doi:10.1126/science.283.5399.186 · Cited by 89
Doll, C. A., & Broadie, K. S. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00030 · Cited by 86
“Crucially, FMRP is locally synthesized in response to mGluR activation (Weiler et al., 1997), and mGluR-mediated hippocampal LTD is exaggerated in Fmr1 KO mice (Huber et al., 2002; Nosyreva and Huber, 2006).”
BackgroundPotential 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 90
Modulation of dADAR-dependent RNA editing by the Drosophila fragile X mental retardation protein
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“Moreover, FMRP is present at synapses, where localized protein translation occurs, and is rapidly translated on metabotropic glutamate receptor (mGluR) stimulatio”
BackgroundBongmba, O. Y. N., Martinez, L. A., Elhardt, M. E., Butler, K., & Tejada-Simon, M. V. (2011) · Brain Research · doi:10.1016/j.brainres.2011.05.020 · Cited by 91
“A large body of data suggests that FMRP is involved in synaptic plasticity and dendrite morphogenesis by regulating protein synthesis of specific mRNAs in response to synaptic stimulation (Weiler et al., 1997; Antar et al., 2005).”
Cardiovascular indices of physiological arousal in boys with fragile X syndrome
Roberts, J. E., Boccia, M. L., Bailey, D. B., Hatton, D. D., & Skinner, M. L. (2001) · Developmental Psychobiology · doi:10.1002/dev.1035 · Cited by 88
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“Both presynaptic and postsynaptic regions retain the ability to display many of the molecular effects that characterize their counterparts in the intact brain, including neurotransmitter release, receptor-mediated signal transduction, and protein synthesis (Weiler et al., 1997).”
BackgroundFragile X syndrome—From genes to cognition
Schneider, A., Hagerman, R. J., & Hessl, D. R. (2009) · Developmental Disabilities Research Reviews · doi:10.1002/ddrr.80 · Cited by 90
Understanding fragile X syndrome: insights from animal models
Bakker, C. E., & Oostra, B. A. (2003) · Cytogenetic and Genome Research · doi:10.1159/000072845 · Cited by 90
“As mentioned before, FMRP is expressed in synapses in response to activation of glutamate receptors by glutamate (Weiler et al., 1997; Weiler and Greenough, 1999) and via a negative inhibition pathway FMRP suppresses translation of mRNA (Laggerbauer et al., 2001; Li et al., 2001; Huber et al.,…”
BackgroundMolecular and cellular genetics of fragile X syndrome
Kaufmann, W. E., & Reiss, A. L. (1999) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19990205)88:1 · Cited by 88
Gatto (2010) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2010.00004 · Cited by 204
“…in Synaptic Neuroscience www.frontiersin.org June 2010 | Volume 2 | Article 4 | 7 transduction stimulates synaptic translation via FMRP (Weiler and Greenough, 1993; Weiler et al., 1997, 2004; Greenough et al., 2001; Job and Eberwine, 2001; Muddashetty et al., 2007; Westmark and Malter, 2007).”
Irwin, S. A., Swain, R. A., Christmon, C. A., Chakravarti, A. B., Weiler, I. J., & Greenough, W. T. (2000) · Neurobiology of Learning and Memory · doi:10.1006/nlme.1999.3914 · Cited by 84
On BC1 RNA and the fragile X mental retardation protein
Iacoangeli, A., Rozhdestvensky, T. S., Dolzhanskaya, N., Tournier, B., Schütt, J., Brosius, J., Denman, R. B., Khandjian, E. W., Kindler, S., & Tiedge, H. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0710991105 · Cited by 83
Defective proteostasis in Alzheimer’s disease
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Fmr1 deficiency promotes age-dependent alterations in the cortical synaptic proteome
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“5D, Lower) revealed that FMRP itself was newly synthesized in WT synaptic neurons in response to mGluR activation (indicated by red arrow), corroborating prior reports (35, 36).”
ResultMazrouï, R. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg335 · Cited by 82
Fragile X mental retardation protein interactions with the microtubule associated protein 1B RNA
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“…rapid increase in FMRP synthesis locally in synaptoneurosomes in response to application of glutamate or metabotropic glutamate receptor (mGluR) agonists (Weiler et al. 1997; Greenough et al. 2001; Hou et al. 2006), indicating a regulation of FMRP concentration in response to synaptic stimulation.”
BackgroundCorrelates across the structural, functional, and molecular phenotypes of fragile X syndrome
Beckel-Mitchener, A. C., & Greenough, W. T. (2004) · Mental Retardation and Developmental Disabilities Research Reviews · doi:10.1002/mrdd.20009 · Cited by 82
Angenstein, F., Evans, A. M., Settlage, R. E., Moran, S. T., Ling, S., Klintsova, A. Y., Shabanowitz, J., Hunt, D. F., & Greenough, W. T. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-20-08827.2002 · Cited by 81
“These results support earlier findings describing polysome aggregation and loading of fragile X mental retardation protein (FMRP)-mRNA into small polysomes after metabotropic glutamate receptor (mGluR) stimulation in a synaptoneurosomal preparation (Weiler and Greenough, 1993; Weiler et al., 1997 ).”
BackgroundResultInfluentialZho, W.-M., You, J.-L., Huang, C., & Hsu, K. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-20-08838.2002 · Cited by 81
“Such a result is in line with the observation that new protein synthesis is stimulated by group I mGluR activation in hippocampal synaptoneurosomes (Weiler et al., 1997; Angenstein et al., 1998).”
ResultDifferential translation and fragile X syndrome
Vanderklish, P. W., & Edelman, G. M. (2005) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2005.00134.x · Cited by 59
“mice (Weiler et al. 1997) and (iii) a translation-dependent elongation of dendritic spines (Vanderklish & Edelman”
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“Moreover, the more recent studies using rat brains have shown that FMRP is involved in synaptogenesis, especially in the cerebral cortex, cerebellum, and hippocampus(27) and in modifying synaptic structure in response to environmental stimulation.(28,29) This explains the existence of the immature synaptic structures…”
BackgroundThe role of fragile X mental retardation protein in major mental disorders
Fatemi, S. H., & Folsom, T. D. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.11.011 · Cited by 80
“However, in neurons, the vast majority of FMRP is localized to the cytoplasm with primary sublocalization to the dendrites, spines, and soma (Bakker et al., 2000; Weiler et al., 1997).”
BackgroundBiology of the fragile X mental retardation protein, an RNA-binding protein
Khandjian, É. W. (1999) · Biochemistry and Cell Biology · doi:10.1139/bcb-77-4-331 · Cited by 81
“Indeed, a rapid localized production of FMRP in synaptosomes in response to neurotransmitter activation has been observed in vitro (Weiler et al. 1997), suggesting that this de novo synthesized FMRP might be necessary to fulfill a function in situ for synaptic activity.”
BackgroundBardoni, B. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg181 · Cited by 79
“In neurons, a minor fraction of FMRP is present in dendrites and this led to the hypothesis that FMRP is involved in translational control at the post-synaptic level (34).”
BackgroundFragile X syndrome at the turn of the century
Kooy, R. F., Willemsen, R., & Oostra, B. A. (2000) · Molecular Medicine Today · doi:10.1016/s1357-4310(00)01674-9 · Cited by 80
DendritesPreprint
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The effect of pre-mutation of X chromosome CGG trinucleotide repeats on brain anatomy
Moore, C. J. (2004) · Brain · doi:10.1093/brain/awh256 · Cited by 75
“, 1993), required for normal synaptic maturation (Weiler et al., 1997).”
BackgroundNeuronal sub‐compartmentalization: a strategy to optimize neuronal function
Donato, A., Kagias, K., Zhang, Y., & Hilliard, M. A. (2019) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/brv.12487 · Cited by 75
Karachot, L., Shirai, Y., Vigot, R., Yamamori, T., & Ito, M. (2001) · Journal of Neurophysiology · doi:10.1152/jn.2001.86.1.280 · Cited by 75
The fragile X mental retardation protein has nucleic acid chaperone properties
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“By analogy with YB-1/ p50, a major cellular chaperone associated with mRNPs (32,39), it can also be envisioned that a low level of FMRP should stimulate translation, whereas a high level of FMRP should mask the mRNA and hence inhibit its translation (20,23,29).”
BackgroundFatimy, R. E., Tremblay, S., Dury, A. Y., Solomon, S., Koninck, P. D., Schrader, J. W., & Khandjian, É. W. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039338 · Cited by 73
Sinakevitch, I. G., Farris, S. M., & Strausfeld, N. J. (2001) · The Journal of Comparative Neurology · doi:10.1002/cne.1355 · Cited by 73
“This occurs locally through metabotropic glutamate receptors that, when activated, trigger a phosphorylation cascade that leads to mRNA translation and protein synthesis at the postsynaptic site (Weiler et al., 1997; Angenstein et al., 1998).”
BackgroundRenoux, A. J., & Todd, P. K. (2011) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2011.10.006 · Cited by 75
A native function for RAN translation and CGG repeats in regulating fragile X protein synthesis
Rodriguez, C. M., Wright, S. E., Kearse, M. G., Haenfler, J. M., Flores, B. N., Liu, Y., Ifrim, M. F., Glineburg, M. R., Krans, A., Jafar‐Nejad, P., et al. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-0590-1 · Cited by 71
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The Thorny Side of Addiction: Adaptive Plasticity and Dendritic Spines
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“Interestingly, polyribosomes redistribute from dendritic shafts into spines with enlarged synapes during LTP[95], and activation of mGluR5 receptors has been observed to rapidly increase the aggregation of polyribosomes[96] and to increase spine size[97].”
BackgroundSignals, synapses, and synthesis: how new proteins control plasticity
Zukin, R. S. (2009) · Frontiers in Neural Circuits · doi:10.3389/neuro.04.014.2009 · Cited by 75
“…al., 2001; Miyashiro et al., 2003; D’Hulst et al., 2006; Zalfa et al., 2007; Zhang et al., 2007) and translational effi ciency of dendritic mRNAs in response to stimulation of mGluRs (Weiler et al., 1997; Todd et al., 2003; Muddashetty et al., 2007; Westmark and Malter, 2007; Napoli et al., 2008).”
Scheetz, A. J., Nairn, A. C., & Constantine‐Paton, M. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.26.14770 · Cited by 70
Protein synthesis in the dendrite
Tang, S. J., & Schuman, E. M. (2002) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2001.0887 · Cited by 72
“One of these proteins might be fragile mental retardation protein (FMRP).”
BackgroundInfluentialUnstable Mutations in the FMR1 Gene and the Phenotypes
Loesch, D. Z., & Hagerman, R. J. (2012) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-5434-2_6 · Cited by 67
Lee, L., Chen, W., Chuang, Y.-W., & Wang, Y. (2009) · Experimental Neurology · doi:10.1016/j.expneurol.2009.07.012 · Cited by 69
“On the other hand, the Fragile X mental retardation protein (FMRP), absent in Fragile X patients, is normally located in the synapse and is important for the integrity of synaptic structure (Weiler et al., 1997).”
Zeier, Z. R., Kumar, A., Bodhinathan, K., Feller, J. A., Foster, T. C., & Bloom, D. C. (2009) · Gene Therapy · doi:10.1038/gt.2009.83 · Cited by 72
Wang, H., Dictenberg, J. B., Ku, L., Li, W., Bassell, G. J., & Feng, Y. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-06-0583 · Cited by 71
“Indeed, dendritic transport of FMRP and Fmr1 mRNA, as well as localized translation of FMRP at the synaptic terminals, can be stimulated by the activation of group I metabotropic glutamate receptors (GP1-mGluRs) (Weiler et al., 1997; Antar et al., 2004; Ferrari et al., 2007).”
BackgroundDavidovic, L., Bechara, E., Gravel, M., Jaglin, X. H., Tremblay, S., Attila Gabor, S. I. K., Bardoni, B., & Khandjian, É. W. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl074 · Cited by 68
“In neurons, polyribosomal aggregates are also present in dendritic spines and synapses and these structures contain FMRP (7,42).”
BackgroundGlycogen Synthase Kinase-3: A Promising Therapeutic Target for Fragile X Syndrome
Mines, M. A., & Jope, R. S. (2011) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2011.00035 · Cited by 68
“These findings may be associated with the detrimental actions of GSK3 in FXS because APP is phosphorylated by GSK3 (Aplin et al., 1996; Wen et al., 2008).”
Verma, V., Paul, A., Vishwanath, A. A., Vaidya, B., & Clement, J. P. (2019) · Open Biology · doi:10.1098/rsob.180265 · Cited by 68
“While the distribution of specific proteins such as FMRP is widespread, the SYNGAP1 protein is expressed only in the brain, not in any other organ [9,10].”
BackgroundSelective translation of mRNAs at synapses
Richter, J. D. (2002) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(02)00318-5 · Cited by 68
Cellular Plasticity for Group I mGluR-Mediated Epileptogenesis
Bianchi, R., Chuang, S.-C., Zhao, W., Young, S. R., & Wong, R. K. S. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.5447-08.2009 · Cited by 67
“This is attributable to the negative regulation of group I mGluRactivated mRNA translation by the fragile X mental retardation protein (FMRP) (Weiler et al., 1997; Huber et al., 2002; Aschrafi et al., 2005; Chuang et al., 2005; Hou et al., 2006).”
InfluentialLi, C. (2009) · Frontiers in Neural Circuits · doi:10.3389/neuro.04.011.2009 · Cited by 67
“Moreover, lack of FMRP impairs the stimulation of protein synthesis downstream of metabotropic glutamate receptors (mGluR) (Weiler et al., 1997; Hou et al., 2006; Muddashetty et al., 2007).”
X‐linked mental retardation: focus on synaptic function and plasticity
Humeau, Y., Gambino, F., Chelly, J., & Vitale, N. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.05881.x · Cited by 76
Huang, J., Ikeuchi, Y., Malumbres, M., & Bonni, A. (2015) · Neuron · doi:10.1016/j.neuron.2015.03.049 · Cited by 66
“Because FMRP undergoes both synthesis and degradation in response to mGluR activation (Hou et al., 2006; Nalavadi et al., 2012; Weiler et al., 1997), to facilitate analysis of FMRP degradation, acute brain slices were pretreated with the protein synthesis inhibitor anisomycin (Nalavadi et al.”
Fathoming fragile X in fruit flies
Zhang, Y., & Broadie, K. S. (2004) · Trends in Genetics · doi:10.1016/j.tig.2004.11.003 · Cited by 66
Pan, L., Woodruff, E. A., Liang, P., & Broadie, K. S. (2008) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2008.01.003 · Cited by 68
“The increase in dFMRP level in the absence of mGluR signaling is somewhat surprising in light of mammalian studies showing that increased synaptic activity increases FMRP expression and, more specifically, that mGluR activation increases FMRP expression (Weiler et al., 1997; Todd et al., 2003).”
Bardoni, B. (2003) · Experimental Cell Research · doi:10.1016/s0014-4827(03)00222-2 · Cited by 66
Veloz, M. F. V., Buijsen, R. A. M., Willemsen, R., Cupido, A., Bosman, L. W. J., Koekkoek, S. K. E., Potters, J.-W., Oostra, B. A., & Zeeuw, C. I. D. (2012) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2011.00763.x · Cited by 70
“2003), is present in the postsynaptic compartment and locally synthesized upon mGluR activation (Weiler et al. 1997).”
BackgroundNeuroanatomical, molecular genetic, and behavioral correlates of fragile X syndrome
Koukoui, S., & Chaudhuri, A. (2006) · Brain Research Reviews · doi:10.1016/j.brainresrev.2006.06.001 · Cited by 65
Fragile X mental retardation protein: A paradigm for translational control by RNA-binding proteins
Chen, E., & Joseph, S. (2015) · Biochimie · doi:10.1016/j.biochi.2015.02.005 · Cited by 66
“Indeed, the levels of FMRP in activated synapses rapidly increase for a short time and then decrease to steady state levels (Hou et al., 2006; Weiler et al., 1997).”
BackgroundChannelopathies and dendritic dysfunction in fragile X syndrome
Brager, D. H., & Johnston, D. (2014) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2014.01.002 · Cited by 65
“Fragile X mental retardation protein FMRP) is highly expressed in neuronal cell bodies and dendrites Steward and Levy, 1982; Feng et al., 1997; Weiler et al., 1997; teward and Schuman, 2001) and binds to the mRNAs for many ∗ Corresponding author at: Center for Learning and Memory University of…”
BackgroundFrank, R. A. W., McRae, A. F., Pocklington, A. J., van de Lagemaat, L. N., Navarro, P., Croning, M. D. R., Komiyama, N. H., Bradley, S. J., Challiss, R. A. J., Armstrong, J. D., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019011 · Cited by 66
“GRM1 has a wellestablished role in the commonest form of mental retardation, Fragile X syndrome [42].”
BackgroundAltered mossy fiber distributions in adult Fmr1 (FVB) knockout mice
Ivanco, T. L., & Greenough, W. T. (2002) · Hippocampus · doi:10.1002/hipo.10004 · Cited by 65
“In synaptoneurosome preparations, which are composed of active, attached, pre- and postsynaptic terminals, FMRP is synthesized at the synapse in response to neurotransmitter stimulation (Weiler et al., 1997).”
BackgroundGroup I Metabotropic Glutamate Receptors: A Role in Neurodevelopmental Disorders?
Catania, M. V., D’Antoni, S., Bonaccorso, C. M., Aronica, E., Bear, M. F., & Nicoletti, F. (2007) · Molecular Neurobiology · doi:10.1007/s12035-007-0022-1 · Cited by 61
“The first indication for a link between mGlu receptors and FRAX was the evidence that activation of group I mGlu receptors stimulates the synthesis of FMRP in synaptoneurosomes [90].”
BackgroundTodd, P. K., & Mack, K. J. (2000) · Molecular Brain Research · doi:10.1016/s0169-328x(00)00098-x · Cited by 69
Psychopathology in the Postgenomic Era
Plomin, R. J., & McGuffin, P. (2002) · Annual Review of Psychology · doi:10.1146/annurev.psych.54.101601.145108 · Cited by 65
Aguilar‐Valles, A., Matta‐Camacho, E., Khoutorsky, A., Gkogkas, C. G., Nader, K., Lacaille, J., & Sonenberg, N. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.4615-14.2015 · Cited by 62
“The compound AFQ056 appeared to improve the behavioral outcome in FXS patients with fully methylated alleles (and no detectable FMR1 mRNA), but not in those with partial methylation (Jacquemont et al., 2011), suggesting that the underlying genetic variability may be important for the responsiveness to treatment.”
BackgroundLoesch, D. Z., Huggins, R., Bui, M., Taylor, A. K., Pratt, C., Epstein, J., & Hagerman, R. J. (2003) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.20214 · Cited by 60
“, 1995], and in modifying synaptic structure in response to environmental stimulation [Weiler et al., 1997; Weiler and Greenough, 1999].”
BackgroundInfluentialEarly identification of autism in fragile X syndrome: a review
McCary, L. M., & Roberts, J. E. (2012) · Journal of Intellectual Disability Research · doi:10.1111/j.1365-2788.2012.01609.x · Cited by 62
“The reduction of FMRP is assumed to be the cause of various outcomes associated with FXS such as intellectual disability, autistic behaviour, social problems and anxiety (Weiler et al. 1997; Bailey et al. 2001b).”
BackgroundFähling, M., Mrowka, R., Steege, A., Kirschner, K. M., Benko, E., Förstera, B., Persson, P. B., Thiele, B. J., Meier, J. C., & Scholz, H. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m807354200 · Cited by 61
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
“Intriguingly, FMRP also binds and regulates the translation of its own mRNA in vitro and FMRP is rapidly synthesized at synapses in response to mGluR activation in vivo (16,17,20,68,72,73).”
BackgroundInfluentialControl of spine maturation and pruning through proBDNF synthesized and released in dendrites
Orefice, L. L., Shih, C., Xu, H., Waterhouse, E. G., & Xu, B. (2015) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2015.12.010 · Cited by 56
“Since FMRP is localized to synapses and is associated with numerous mRNAs, it is thought that FMRP affects the structure and function of postsynaptic sites by regulating dendritic protein synthesis (Weiler et al., 1997; Zalfa et al., 2003).”
BackgroundIvanco, T. L., & Greenough, W. T. (2000) · Neuropharmacology · doi:10.1016/s0028-3908(00)00004-6 · Cited by 57
Translational control at the synapse: role of RNA regulators
Iacoangeli, A., & Tiedge, H. (2012) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2012.11.001 · Cited by 57
Some problems in the genetics of X-linked mental retardation
Tariverdian, G., & Vogel, F. (2000) · Cytogenetic and Genome Research · doi:10.1159/000056857 · Cited by 55
Ohashi, S., Kobayashi, S., Omori, A., Ohara, S., Omae, A., Muramatsu, T., Li, Y., & Anzai, K. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0751781.x · Cited by 56
Metadata
- Authors
- Weiler, 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.
- Affiliations
- University of Illinois Urbana-Champaign (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1997-05-13
- Volume
- 94
- Issue
- 10
- Pages
- 5395-5400
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC24689
- OpenAlex
- W2002760096
- Cited by
- 644
- References
- 58
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 8 · 2023: 11 · 2022: 11 · 2021: 12 · 2020: 8 · 2019: 14 · 2018: 13 · 2017: 19 · 2016: 15 · 2015: 23 · 2014: 24 · 2013: 27 · 2012: 29
- FWCI
- 12.99
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- FRAXA Research Foundation (MH35321)
- John D. and Catherine T. MacArthur Foundation
- National Institutes of Health
- U.S. Public Health Service
- National Institute on Aging (AG10154, R01AG010154)
- National Institute of Mental Health (MH-35321, R01MH035321, R37MH035321)
- National Center for Research Resources (RR 04050, P41RR004050)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- FMRP, local protein synthesis, metabotropic glutamate receptor 1, polysomes, synaptoneurosomes, dendritic mRNA, synapse maturation, synaptic plasticity, dendritic translation
- MeSH terms
- Amino Acid Sequence, Animals, Antibodies, Brain, Dendrites, Glycine, Humans, Kinetics, Molecular Sequence Data, Nerve Tissue Proteins, Neurons, Organ Specificity, Polyribosomes, Resorcinols, RNA, Messenger, Synapses, Protein Biosynthesis, Oligonucleotide Probes, Gene Library, Antisense Elements (Genetics), RNA-Binding Proteins, Sequence Homology, Amino Acid, DNA, Complementary, Receptors, Metabotropic Glutamate, Neurotransmitter Agents, Excitatory Amino Acid Antagonists, Rats, Fragile X Mental Retardation Protein, Fragile X Messenger Ribonucleoprotein 1
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