The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
S6K1 Phosphorylates and Regulates Fragile X Mental Retardation Protein (FMRP) with the Neuronal Protein Synthesis-dependent Mammalian Target of Rapamycin (mTOR) Signaling Cascade
Open accessAbstract
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Citations
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
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
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 1,130
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
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
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
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 766
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
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
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
Flagged first, then by citations
Cited by
Sorted by citations
Items 201–216 of 216
Denman, R. B. (2011) · Results and problems in cell differentiation · doi:10.1007/978-3-642-21649-7_19
Araque, E. V., Rengifo, J., & Becerra-Hernández, L. V. (2020) · Universitas Médica · doi:10.11144/javeriana.umed61-4.fmrp · Cited by 2
Khlebodarova, T. M. (2021) · Vavilov Journal of Genetics and Breeding · doi:10.18699/vj21.011
Nairn, A. C., & Wiseman, S. L. (2011) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.13385959.14754080
Pavan, I. C. B., Silva, F. R., Morelli, A. P., & Simabuco, F. M. (2017) · Springer eBooks · doi:10.1007/978-3-319-67199-4_101816
FMRP dependent synaptic delivery of messenger RNA
Kao, D.-I. (2011) · Illinois Digital Environment for Access to Learning and Scholarship (University of Illinois at Urbana-Champaign)
Yang, W.-J., Yan, A.-Z., Xu, Y.-J., Guo, X.-Y., Fu, X.-G., Li, D., Liao, J., Zhang, D., & 兰风华 (2020) · Figshare · doi:10.6084/m9.figshare.12511331
Schorova, L. (2018) · theses.fr (ABES) · doi:10.70675/a30a505az5e81z4089za24azcf43d27e33ce
The role of intrinsic neuronal excitability for Prelimbic network function
Sa, R. D. (2019) · theses.fr (ABES) · doi:10.70675/8b11b402z0ae7z4587z8084z65b59ce7ba62
Dissecting the role of calcium signaling in Fragile X syndrome
Castagnola, S. (2019) · theses.fr (ABES) · doi:10.70675/3d35096bz79d0z46edz8a70zb783a8f60257
Pathophysiological consequences of a Fragile X missense mutation
Garcia, M. P. (2020) · theses.fr (ABES) · doi:10.70675/b8e86263z5926z4a83zbaf6z0f61bf2d15f9
Role of the mTOR-downstream effector S6K1 in tuberous sclerosis complex neurological manifestations
Avanzi, F. (2023) · theses.fr (ABES) · doi:10.70675/20853cbdz078bz47dcza392zaeb61eb11f48
Wolozin, B. L., Best, M. N., Ellini, M., Ma, Y., Bok, S., Hwang, D., & Filipponi, C. (2026) · Cells · doi:10.3390/cells15171596
Jastrzębski, K., Kacperska, M. J., Pietras, T., & Radek, M. (2013) · DOAJ (DOAJ: Directory of Open Access Journals)
Metadata
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
