The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index.
Independent role for presynaptic FMRP revealed by an FMR1 missense mutation associated with intellectual disability and seizures
Open accessAbstract
Fragile X syndrome (FXS) results in intellectual disability (ID) most often caused by silencing of the fragile X mental retardation 1 (FMR1) gene. The resulting absence of fragile X mental retardation protein 1 (FMRP) leads to both pre- and postsynaptic defects, yet whether the pre- and postsynaptic functions of FMRP are independent and have distinct roles in FXS neuropathology remain poorly understood. Here, we demonstrate an independent presynaptic function for FMRP through the study of an ID patient with an FMR1 missense mutation. This mutation, c.413G > A (R138Q), preserves FMRP's canonical functions in RNA binding and translational regulation, which are traditionally associated with postsynaptic compartments. However, neuronally driven expression of the mutant FMRP is unable to rescue structural defects at the neuromuscular junction in fragile x mental retardation 1 (dfmr1)-deficient Drosophila, suggesting a presynaptic-specific impairment. Furthermore, mutant FMRP loses the ability to rescue presynaptic action potential (AP) broadening in Fmr1 KO mice. The R138Q mutation also disrupts FMRP's interaction with the large-conductance calcium-activated potassium (BK) channels that modulate AP width. These results reveal a presynaptic- and translation-independent function of FMRP that is linked to a specific subset of FXS phenotypes.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The cited source says what the claim attributes to it.
In the citing paper
“and a translation-independent function was also described for FMRP (Myrick et al., 2015).”
From New insights into the regulatory function of CYFIP1 in the context of WAVE- and FMRP-containing complexes (2017) · cites this paper as Myrick et al., 2015
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Fu, Y.-H., Kuhl, D. P. A., Pizzuti, A., Pieretti, M., Sutcliffe, J. S., Richards, S., Verkert, A. J. M. H., Holden, J. J. A., Fenwick, R. G., Warren, S. T., et al. (1991) · Cell · doi:10.1016/0092-8674(91)90283-5 · Cited by 2,080
Self-citationAltered synaptic plasticity in a mouse model of fragile X mental retardation
Huber, K. M., Gallagher, S. M., Warren, S. T., & Bear, M. F. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.122205699 · Cited by 1,349
Self-citationFragile 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
Self-citationZhang, Y., Bailey, A. M., Matthies, H. J. G., Renden, R., Smith, M. A., Speese, S. D., Rubin, G. M., & Broadie, K. S. (2001) · Cell · doi:10.1016/s0092-8674(01)00589-x · Cited by 651
A point mutation in the FMR-1 gene associated with fragile X mental retardation
Boulle, K. D., Verkerk, A. J. M. H., Reyniers, E., Vits, L., Hendrickx, J., Roy, B. V., Bos, F. V. D., de Graaff, E., Oostra, B. A., & Willems, P. J. (1993) · Nature Genetics · doi:10.1038/ng0193-31 · Cited by 624
Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder
Du, W., Bautista, J. F., Yang, H., Dı́ez-Sampedro, A., You, S.-A., Wang, L., Kotagal, P., Lüders, H. O., Shi, J., Cui, J., et al. (2005) · Nature Genetics · doi:10.1038/ng1585 · Cited by 578
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
Self-citationThe Tudor domain ‘Royal Family’: Tudor, plant Agenet, Chromo, PWWP and MBT domains
Maurer‐Stroh, S., Dickens, N. J., Hughes‐Davies, L., Kouzarides, T., Eisenhaber, F., & Ponting, C. P. (2003) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(03)00004-5 · Cited by 482
Recognition of unmethylated histone H3 lysine 4 links BHC80 to LSD1-mediated gene repression
Lan, F., Collins, R. E., Cegli, R. D., Alpatov, R., Horton, J. R., Shi, X., Gozani, O., Cheng, X., & Shi, Y. (2007) · Nature · doi:10.1038/nature06034 · Cited by 432
Self-citationMuddashetty, R. S., Kelić, S., Gross, C., Xu, M., & Bassell, G. J. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.0937-07.2007 · Cited by 421
Osterweil, E. K., Krueger, D. D., Reinhold, K., & Bear, M. F. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.3888-10.2010 · Cited by 384
BK channel β4 subunit reduces dentate gyrus excitability and protects against temporal lobe seizures
Brenner, R., Chen, Q. H., Vilaythong, A., Toney, G. M., Noebels, J. L., & Aldrich, R. W. (2005) · Nature Neuroscience · doi:10.1038/nn1573 · Cited by 358
Schenck, A., Bardoni, B., Moro, A., Bagni, C., & Mandel, J.-L. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.151231598 · Cited by 356
Deng, P.-Y., Rotman, Z., Blundon, J. A., Cho, Y., Cui, J., Cavalli, V., Zakharenko, S. S., & Klyachko, V. A. (2013) · Neuron · doi:10.1016/j.neuron.2012.12.018 · Cited by 354
Self-citationHu, H., Shao, L.-R., Chavoshy, S., Gu, N., Trieb, M., Behrens, R., Laake, P., Pongs, O., Knaus, H., Ottersen, O. P., et al. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-24-09585.2001 · Cited by 340
Wan, L., Dockendorff, T. C., Jongens, T. A., & Dreyfuss, G. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.22.8536-8547.2000 · Cited by 280
Fragile X mental retardation protein is associated with translating polyribosomes in neuronal cells
Stefani, G., Fraser, C. E., Darnell, J. C., & Darnell, R. B. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.2306-04.2004 · Cited by 274
Siomi, M. C., Zhang, Y., Siomi, H., & Dreyfuss, G. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.7.3825 · Cited by 271
Calcium-Activated Potassium Channels: Multiple Contributions to Neuronal Function
Faber, E. S. L., & Sah, P. (2003) · The Neuroscientist · doi:10.1177/1073858403009003011 · Cited by 267
Fragile X mental retardation protein controls gating of the sodium-activated potassium channel Slack
Brown, M. R., Kronengold, J., Gazula, V., Chen, Y., Strumbos, J. G., Sigworth, F. J., Navaratnam, D. S., & Kaczmarek, L. K. (2010) · Nature Neuroscience · doi:10.1038/nn.2563 · Cited by 261
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
Self-citationThe FXG: a presynaptic fragile X granule expressed in a subset of developing brain circuits
Christie, S. B., Akins, M. R., Schwob, J. E., & Fallon, J. R. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.3937-08.2009 · Cited by 208
The Drosophila Fragile X Gene Negatively Regulates Neuronal Elaboration and Synaptic Differentiation
Pan, L., Zhang, Y., Woodruff, E. A., & Broadie, K. S. (2004) · Current Biology · doi:10.1016/j.cub.2004.09.085 · Cited by 197
Cavalleri, G. L., Weale, M. E., Shianna, K. V., Singh, R., Lynch, J. M., Grinton, B. E., Szoeke, C. E. I., Murphy, K. C., Kinirons, P., O’Rourke, D., et al. (2007) · The Lancet Neurology · doi:10.1016/s1474-4422(07)70247-8 · Cited by 188
FMRP Acts as a Key Messenger for Dopamine Modulation in the Forebrain
Wang, H., Wu, L.-J., Kim, S. S., Lee, F. J. S., Gong, B., Toyoda, H., Ren, M., Shang, Y.-Z., Xu, H., Liu, F., et al. (2008) · Neuron · doi:10.1016/j.neuron.2008.06.027 · Cited by 186
Laumonnier, F., Roger, S., Guérin, P., Molinari, F., Mrad, R., Cahard, D., Belhadj, A., Halayem, M. B., Persico, A. M., Elia, M., et al. (2006) · American Journal of Psychiatry · doi:10.1176/ajp.2006.163.9.1622 · Cited by 184
Alpatov, R., Lesch, B. J., Nakamoto-Kinoshita, M., Blanco, M. A., Chen, S., Stützer, A., Armache, K., Simon, M. D., Xu, C., Ali, M., et al. (2014) · Cell · doi:10.1016/j.cell.2014.03.040 · Cited by 175
Self-citationVolk, L. J., Pfeiffer, B. E., Gibson, J. R., & Huber, K. M. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.2266-07.2007 · Cited by 166
Gross, C., Yao, X., Pong, D. L., Jeromin, A., & Bassell, G. J. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.6661-10.2011 · Cited by 161
Lee, H. Y., Ge, W., Huang, W. C., He, Y., Wang, G. X., Rowson-Baldwin, A., Smith, S. J., Jan, Y. N., & Jan, L. Y. (2011) · Neuron · doi:10.1016/j.neuron.2011.09.033 · Cited by 153
Predicting the diagnosis of autism spectrum disorder using gene pathway analysis
Skafidas, E. S., Testa, R., Zantomio, D., Chana, G., Everall, I., & Pantelis, C. (2012) · Molecular Psychiatry · doi:10.1038/mp.2012.126 · Cited by 148
Ferron, L., Nieto‐Rostro, M., Cassidy, J. S., & DOLPHIN, A. C. (2014) · Nature Communications · doi:10.1038/ncomms4628 · Cited by 140
A mouse model of the human Fragile X syndrome I304N mutation
Zang, J. B., Nosyreva, E. D., Spencer, C. M., Volk, L. J., Musunuru, K., Zhong, R., Stone, E. F., Yuva-Paylor, L. A., Huber, K. M., Paylor, R., et al. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000758 · Cited by 138
Suvrathan, A., Hoeffer, C. A., Wong, H., Klann, E., & Chattarji, S. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1002262107 · Cited by 137
Bardoni, B., Schenck, A., & Louis Mandel, J. (1999) · Human Molecular Genetics · doi:10.1093/hmg/8.13.2557 · Cited by 136
Strumbos, J. G., Brown, M. R., Kronengold, J., Polley, D. B., & Kaczmarek, L. K. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.1125-10.2010 · Cited by 135
Zhang, Y., Brown, M. R., Hyland, C., Chen, Y., Kronengold, J., Fleming, M. R., Kohn, A. B., Moroz, L. L., & Kaczmarek, L. K. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.2162-12.2012 · Cited by 127
Collins, S. C., Bray, S. M., Suhl, J. A., Cutler, D. J., Coffee, B. W., Zwick, M. E., & Warren, S. T. (2010) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.33626 · Cited by 126
Self-citationRamos, A., Hollingworth, D., Adinolfi, S., Castets, M., Kelly, G. P., Frenkiel, T. A., Bardoni, B., & Pastore, A. (2006) · Structure · doi:10.1016/j.str.2005.09.018 · Cited by 115
Fragile X syndrome due to a missense mutation
Myrick, L. K., Nakamoto-Kinoshita, M., Lindor, N. M., Kirmani, S., Cheng, X., & Warren, S. T. (2014) · European Journal of Human Genetics · doi:10.1038/ejhg.2013.311 · Cited by 109
Self-citationHanson, J. E., & Madison, D. V. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.4717-06.2007 · Cited by 103
Gatto, C. L., & Broadie, K. S. (2008) · Development · doi:10.1242/dev.022244 · Cited by 102
Targeting BK (big potassium) channels in epilepsy
N’Gouemo, P. (2011) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2011.620607 · Cited by 89
Patel, A. B., Hays, S. A., Bureau, I., Huber, K. M., & Gibson, J. R. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.2447-12.2013 · Cited by 82
Higgins, J. J., Hao, J., Kosofsky, B. E., & Rajadhyaksha, A. M. (2008) · Neurogenetics · doi:10.1007/s10048-008-0128-2 · Cited by 79
Bardoni, B. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg181 · Cited by 79
Akins, M. R., LeBlanc, H. F., Stackpole, E. E., Chyung, E., & Fallon, J. R. (2012) · The Journal of Comparative Neurology · doi:10.1002/cne.23123 · Cited by 78
Tremorgenic mycotoxin intoxication with penitrem A and roquefortine in two dogs
Young, K. L., Villar, D., Carson, T. L., Imerman, P. M., Moore, R. A., & Bottoff, M. R. (2003) · Journal of the American Veterinary Medical Association · doi:10.2460/javma.2003.222.52 · Cited by 60
Todd, P. K., Malter, J. S., & Mack, K. J. (2003) · Molecular Brain Research · doi:10.1016/s0169-328x(02)00657-5 · Cited by 56
Down-regulation of BK channel expression in the pilocarpine model of temporal lobe epilepsy
Otalora, L. F. P., Hernandez, E. F., Arshadmansab, M. F., Francisco, S., Willis, M., Ermolinsky, B. S., Zarei, M. M., Knaus, H., & Garrido-Sanabria, E. R. (2008) · Brain Research · doi:10.1016/j.brainres.2008.01.017 · Cited by 56
Martire, M., Barrese, V., D’Amico, M., Iannotti, F. A., Pizzarelli, R., Samengo, I. A., Viggiano, D., Ruth, P., Cherubini, E., & Taglialatela, M. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06938.x · Cited by 49
The fragile X–cerebellum connection
Huber, K. M. (2006) · Trends in Neurosciences · doi:10.1016/j.tins.2006.02.001 · Cited by 48
A presynaptic role for FMRP during protein synthesis–dependent long-term plasticity in AplysiaPreprint
Till, S. M., Li, H.-L., Miniaci, M. C., Kandel, E. R., & Choi, Y. (2010) · Learning & Memory · doi:10.1101/lm.1958811 · Cited by 30
Deficit of Kcnma1 mRNA expression in the dentate gyrus of epileptic rats
Ermolinsky, B. S., Arshadmansab, M. F., Otalora, L. F. P., Zarei, M. M., & Garrido-Sanabria, E. R. (2008) · Neuroreport · doi:10.1097/wnr.0b013e3283094bb6 · Cited by 24
Wang, H., Fukushima, H., Kida, S., & Zhuo, M. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.019141 · Cited by 23
Deng, P., Rotman, Z., Blundon, J. A., Cho, Y., Cui, J., Cavalli, V., Zakharenko, S. S., & Klyachko, V. A. (2013) · Neuron · doi:10.1016/j.neuron.2013.03.027 · Cited by 7
Self-citation
Cited by
Sorted by citations
Hagerman, R. J., Berry-Kravis, E., Hazlett, H. C., Bailey, D. B., Moine, H., Kooy, R. F., Tassone, F., Gantois, I., Sonenberg, N., Mandel, J. L., et al. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.65 · Cited by 838
Altered Neuronal and Circuit Excitability in Fragile X Syndrome
Contractor, A., Klyachko, V. A., & Portera‐Cailliau, C. (2015) · Neuron · doi:10.1016/j.neuron.2015.06.017 · Cited by 418
Self-citationDysregulation and restoration of translational homeostasis in fragile X syndrome
Richter, J. D., Bassell, G. J., & Klann, E. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn4001 · Cited by 275
BK Channels in the Central Nervous System
Contet, C., Goulding, S. P., Kuljis, D. A., & Barth, A. L. (2016) · International review of neurobiology · doi:10.1016/bs.irn.2016.04.001 · Cited by 180
Sensory Processing Phenotypes in Fragile X Syndrome
Rais, M., Binder, D. K., Razak, K. A., & Ethell, I. M. (2018) · ASN NEURO · doi:10.1177/1759091418801092 · Cited by 143
Metadata
- Authors
- Myrick, L. K., Deng, P.-Y., Hashimoto, H., Oh, Y. M., Cho, Y., Poidevin, M. J., Suhl, J. A., Visootsak, J., Cavalli, V., Jin, P., Cheng, X., Warren, S. T., & Klyachko, V. A.
- Affiliations
- Emory University (US)
- Departments of bBiomedical Engineering and Cell Biology and Physiology and
- Washington University in St. Louis (US)
- Departments of aHuman Genetics,
- Biochemistry, and
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2015-01-05
- Volume
- 112
- Issue
- 4
- Pages
- 949-956
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4313821
- OpenAlex
- W1979762144
- Cited by
- 133
- References
- 56
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 8 · 2023: 7 · 2022: 8 · 2021: 11 · 2020: 8 · 2019: 14 · 2018: 18 · 2017: 14 · 2016: 13 · 2015: 13
- FWCI
- 13.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Institute of Neurological Disorders and Stroke (1U54NS091859, NS089449)
- HHS | NIH | National Institute of General Medical Sciences (GM049245)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Keywords
- FMRP, FMR1 gene, fragile X syndrome, presynaptic function, missense mutations, intellectual disability, seizures, neuromuscular junction, action potential broadening, BK channels, translational regulation, RNA binding, Drosophila, Fmr1 knockout mice
- MeSH terms
- Action Potentials, Animals, Child, Child, Preschool, Drosophila, Fragile X Syndrome, Gene Expression Regulation, Humans, Male, Seizures, Amino Acid Substitution, Mutation, Missense, Mice, Fragile X Messenger Ribonucleoprotein 1
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
