fragile x mental retardation protein

Summary

Summary: A RNA-binding protein that is found predominately in the CYTOPLASM. It helps regulate GENETIC TRANSLATION in NEURONS and is absent or under-expressed in FRAGILE X SYNDROME.

Top Publications

  1. Connor S, Hoeffer C, Klann E, Nguyen P. Fragile X mental retardation protein regulates heterosynaptic plasticity in the hippocampus. Learn Mem. 2011;18:207-20 pubmed publisher
    ..The FMR1 gene encodes fragile X mental retardation protein (FMRP), which negatively regulates translation...
  2. Chen E, Sharma M, Shi X, Agrawal R, Joseph S. Fragile X mental retardation protein regulates translation by binding directly to the ribosome. Mol Cell. 2014;54:407-417 pubmed publisher
    ..the most common form of inherited mental retardation, and it is caused by loss of function of the fragile X mental retardation protein (FMRP)...
  3. Monaghan K, Lyon E, Spector E. ACMG Standards and Guidelines for fragile X testing: a revision to the disease-specific supplements to the Standards and Guidelines for Clinical Genetics Laboratories of the American College of Medical Genetics and Genomics. Genet Med. 2013;15:575-86 pubmed publisher
    ..In addition to report elements, examples of laboratory reports for various genotypes are also included. ..
  4. Bagni C, Tassone F, Neri G, Hagerman R. Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics. J Clin Invest. 2012;122:4314-22 pubmed publisher
    ..Additionally, behavioral, pharmacological, and cognitive interventions can raise the quality of life for both patients and their families. ..
  5. Keri S, Benedek G. Why is vision impaired in fragile X premutation carriers? The role of fragile X mental retardation protein and potential FMR1 mRNA toxicity. Neuroscience. 2012;206:183-9 pubmed publisher
    ..Although both elevated FMR1 mRNA and reduced fragile X mental retardation protein (FMRP) levels were associated with impaired visual functions, regression analysis indicated that ..
  6. Santoro M, Bray S, Warren S. Molecular mechanisms of fragile X syndrome: a twenty-year perspective. Annu Rev Pathol. 2012;7:219-45 pubmed publisher
    ..Studies continue to refine our understanding of FMRP's role in synaptic plasticity and to uncover new functions of this protein, which have illuminated therapeutic approaches for FXS...
  7. Price T, Melemedjian O. Fragile X mental retardation protein (FMRP) and the spinal sensory system. Results Probl Cell Differ. 2012;54:41-59 pubmed publisher
    The purpose of this chapter is to discuss the role of the fragile X mental retardation protein (FMRP) in the spinal sensory system and the potential for use of the mouse model of fragile X syndrome to better understand some aspects of the ..
  8. Deng P, Sojka D, Klyachko V. Abnormal presynaptic short-term plasticity and information processing in a mouse model of fragile X syndrome. J Neurosci. 2011;31:10971-82 pubmed publisher
    ..It is associated with the lack of fragile X mental retardation protein (FMRP), a regulator of protein synthesis in axons and dendrites...
  9. Siller S, Broadie K. Neural circuit architecture defects in a Drosophila model of Fragile X syndrome are alleviated by minocycline treatment and genetic removal of matrix metalloproteinase. Dis Model Mech. 2011;4:673-85 pubmed publisher
    ..These results support minocycline as a promising potential FXS treatment and suggest that it might act via MMP inhibition. We conclude that FMRP and TIMP pathways interact in a reciprocal, bidirectional manner...

More Information

Publications62

  1. Thomas A, Bui N, Graham D, Perkins J, Yuva Paylor L, Paylor R. Genetic reduction of group 1 metabotropic glutamate receptors alters select behaviors in a mouse model for fragile X syndrome. Behav Brain Res. 2011;223:310-21 pubmed publisher
    ..Therefore, the goals for this study were to extend our understanding of the effects of modulating Gp1 mGluR activity on Fmr1 KO behavioral responses...
  2. Hessl D, Wang J, Schneider A, Koldewyn K, Le L, Iwahashi C, et al. Decreased fragile X mental retardation protein expression underlies amygdala dysfunction in carriers of the fragile X premutation. Biol Psychiatry. 2011;70:859-65 pubmed publisher
    ..Although both elevated FMR1 messenger RNA and reduced fragile X mental retardation protein (FMRP) were associated with the reduced activation, multiple regression analysis suggested that ..
  3. Hagerman R, LAUTERBORN J, Au J, Berry Kravis E. Fragile X syndrome and targeted treatment trials. Results Probl Cell Differ. 2012;54:297-335 pubmed publisher
    ..The lack of Fragile X Mental Retardation Protein (FMRP) in FXS causes dysregulation and usually overexpression of a number of its target genes, ..
  4. Sullivan S, Welt C, Sherman S. FMR1 and the continuum of primary ovarian insufficiency. Semin Reprod Med. 2011;29:299-307 pubmed publisher
    ..Understanding the mechanisms responsible for development of FXPOI is paramount to providing these women with the best overall health care. ..
  5. Paluszkiewicz S, Martin B, Huntsman M. Fragile X syndrome: the GABAergic system and circuit dysfunction. Dev Neurosci. 2011;33:349-64 pubmed publisher
    ..Finally, we highlight the GABAergic system as a relevant target for the treatment of FXS...
  6. Westmark C, Westmark P, O Riordan K, Ray B, Hervey C, Salamat M, et al. Reversal of fragile X phenotypes by manipulation of A?PP/A? levels in Fmr1KO mice. PLoS ONE. 2011;6:e26549 pubmed publisher
    ..b>Fragile X mental retardation protein (FMRP), which is absent or expressed at substantially reduced levels in FXS, binds to and controls ..
  7. Todd P, Oh S, Krans A, He F, Sellier C, Frazer M, et al. CGG repeat-associated translation mediates neurodegeneration in fragile X tremor ataxia syndrome. Neuron. 2013;78:440-55 pubmed publisher
    ..These studies expand the growing list of nucleotide repeat disorders in which RAN translation occurs and provide evidence that RAN translation contributes to neurodegeneration. ..
  8. Chen L, HADD A, Sah S, Houghton J, Filipovic Sadic S, Zhang W, et al. High-resolution methylation polymerase chain reaction for fragile X analysis: evidence for novel FMR1 methylation patterns undetected in Southern blot analyses. Genet Med. 2011;13:528-538 pubmed publisher
    ..In addition, the identification of novel methylation mosaic patterns revealed after polymerase chain reaction and capillary electrophoresis may be relevant to several FMR1 disorders. ..
  9. Ronesi J, Collins K, Hays S, Tsai N, Guo W, Birnbaum S, et al. Disrupted Homer scaffolds mediate abnormal mGluR5 function in a mouse model of fragile X syndrome. Nat Neurosci. 2012;15:431-40, S1 pubmed publisher
    ..altered mGluR-dependent long-term synaptic depression or translational control of target mRNAs of fragile X mental retardation protein, the gene product of Fmr1...
  10. Bhakar A, Dolen G, Bear M. The pathophysiology of fragile X (and what it teaches us about synapses). Annu Rev Neurosci. 2012;35:417-43 pubmed publisher
    ..it typically results from transcriptional silencing of FMR1 and loss of the encoded protein, FMRP (fragile X mental retardation protein)...
  11. Yu Z, Fan D, Gui B, Shi L, Xuan C, Shan L, et al. Neurodegeneration-associated TDP-43 interacts with fragile X mental retardation protein (FMRP)/Staufen (STAU1) and regulates SIRT1 expression in neuronal cells. J Biol Chem. 2012;287:22560-72 pubmed publisher
    ..Here, we report that TDP-43 is physically associated with fragile X mental retardation protein (FMRP) and Staufen (STAU1) to form a functional complex...
  12. Seixas A, Vale J, Jorge P, Marques I, Santos R, Alonso I, et al. FXTAS is rare among Portuguese patients with movement disorders: FMR1 premutations may be associated with a wider spectrum of phenotypes. Behav Brain Funct. 2011;7:19 pubmed publisher
    ..In conclusion, genetic testing for FXTAS should be made available to patients with adult-onset movement disorders to enable adequate genetic counseling to family members. ..
  13. Iossifov I, Ronemus M, Levy D, Wang Z, Hakker I, Rosenbaum J, et al. De novo gene disruptions in children on the autistic spectrum. Neuron. 2012;74:285-99 pubmed publisher
    ..We find FMRP-associated genes are under greater purifying selection than the remainder of genes and suggest they are especially dosage-sensitive targets of cognitive disorders. ..
  14. Lee H, Ge W, Huang W, He Y, Wang G, Rowson Baldwin A, et al. Bidirectional regulation of dendritic voltage-gated potassium channels by the fragile X mental retardation protein. Neuron. 2011;72:630-42 pubmed publisher
    ..potassium channel, which regulates synaptic plasticity, and its local translational regulation by fragile X mental retardation protein (FMRP) linked to fragile X syndrome (FXS), the most common heritable mental retardation...
  15. El Fatimy R, Tremblay S, Dury A, Solomon S, De Koninck P, Schrader J, et al. Fragile X mental retardation protein interacts with the RNA-binding protein Caprin1 in neuronal RiboNucleoProtein complexes [corrected]. PLoS ONE. 2012;7:e39338 pubmed publisher
    Fragile X syndrome is caused by the absence of the Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein...
  16. Bhattacharya A, Kaphzan H, Alvarez Dieppa A, Murphy J, Pierre P, Klann E. Genetic removal of p70 S6 kinase 1 corrects molecular, synaptic, and behavioral phenotypes in fragile X syndrome mice. Neuron. 2012;76:325-37 pubmed publisher
    ..Our results support the model that dysregulated protein synthesis is the key causal factor in FXS and that restoration of normal translation can stabilize peripheral and neurological function in FXS. ..
  17. Kim M, Ceman S. Fragile X mental retardation protein: past, present and future. Curr Protein Pept Sci. 2012;13:358-71 pubmed
    ..The domain features of the fragile X mental retardation protein FMRP are described, as are the mRNAs bound by FMRP and the role of post-translational modifications ..
  18. Portera Cailliau C. Which comes first in fragile X syndrome, dendritic spine dysgenesis or defects in circuit plasticity?. Neuroscientist. 2012;18:28-44 pubmed publisher
    ..spine shape/dynamics and long-term synaptic plasticity (both of which involve proteins regulated by fragile X mental retardation protein [FMRP]), it is argued that the two defects cannot be separated...
  19. Sidorov M, Auerbach B, Bear M. Fragile X mental retardation protein and synaptic plasticity. Mol Brain. 2013;6:15 pubmed publisher
    ..Synthesis of these proteins is required for the maintenance and regulation of long-lasting changes in synaptic strength. In this role as a translational inhibitor, FMRP exerts profound effects on synaptic plasticity. ..
  20. Paluszkiewicz S, Olmos Serrano J, Corbin J, Huntsman M. Impaired inhibitory control of cortical synchronization in fragile X syndrome. J Neurophysiol. 2011;106:2264-72 pubmed publisher
    ..Together, these findings reveal a functional defect in a single subtype of cortical interneuron in Fmr1 KO mice. This defect is linked to altered activity of the cortical network in line with the FXS phenotype. ..
  21. Gleicher N, Weghofer A, Barad D. Cutting edge assessment of the impact of autoimmunity on female reproductive success. J Autoimmun. 2012;38:J74-80 pubmed publisher
    ..Further investigations must not ignore patient stratification, based on ovarian FMR1 genotypes. Genetic definition of high-risk patients should lead to development of successful therapeutic interventions. ..
  22. Gareau C, Houssin E, Martel D, Coudert L, Mellaoui S, Huot M, et al. Characterization of fragile X mental retardation protein recruitment and dynamics in Drosophila stress granules. PLoS ONE. 2013;8:e55342 pubmed publisher
    ..To our knowledge, this is the first demonstration of the regulated shuttling activity of a SG component between RNA granules and the cytosol. ..
  23. Klemmer P, Meredith R, Holmgren C, Klychnikov O, Stahl Zeng J, Loos M, et al. Proteomics, ultrastructure, and physiology of hippocampal synapses in a fragile X syndrome mouse model reveal presynaptic phenotype. J Biol Chem. 2011;286:25495-504 pubmed publisher
    ..mental retardation, is caused by a loss-of-function mutation of the Fmr1 gene, which encodes fragile X mental retardation protein (FMRP). FMRP affects dendritic protein synthesis, thereby causing synaptic abnormalities...
  24. Yrigollen C, Durbin Johnson B, Gane L, Nelson D, Hagerman R, Hagerman P, et al. AGG interruptions within the maternal FMR1 gene reduce the risk of offspring with fragile X syndrome. Genet Med. 2012;14:729-36 pubmed publisher
    ..2 AGG) exceeding 60% for alleles in the 70- to 80-CGG repeat range. ..
  25. Janusz A, Milek J, Perycz M, Pacini L, Bagni C, Kaczmarek L, et al. The Fragile X mental retardation protein regulates matrix metalloproteinase 9 mRNA at synapses. J Neurosci. 2013;33:18234-41 pubmed publisher
    ..We propose that such a local effect can contribute to the aberrant dendritic spine morphology observed in the Fmr1 knock-out mice and in patients with FXS. ..
  26. Wang T, Bray S, Warren S. New perspectives on the biology of fragile X syndrome. Curr Opin Genet Dev. 2012;22:256-63 pubmed publisher
    ..In addition, studies on FXS stem cells especially induced pluripotent stem (iPS) cells and new sequencing efforts hold out promise for deeper understanding of the silencing process and mutation spectrum of FMR1. ..
  27. Kanellopoulos A, Semelidou O, Kotini A, Anezaki M, Skoulakis E. Learning and memory deficits consequent to reduction of the fragile X mental retardation protein result from metabotropic glutamate receptor-mediated inhibition of cAMP signaling in Drosophila. J Neurosci. 2012;32:13111-24 pubmed
    Loss of the RNA-binding fragile X protein [fragile X mental retardation protein (FMRP)] results in a spectrum of cognitive deficits, the fragile X syndrome (FXS), while aging individuals with decreased protein levels present with a subset ..
  28. Auerbach B, Osterweil E, Bear M. Mutations causing syndromic autism define an axis of synaptic pathophysiology. Nature. 2011;480:63-8 pubmed publisher
    ..Thus, normal synaptic plasticity and cognition occur within an optimal range of metabotropic glutamate-receptor-mediated protein synthesis, and deviations in either direction can lead to shared behavioural impairments. ..
  29. Darnell J, Van Driesche S, Zhang C, Hung K, Mele A, Fraser C, et al. FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism. Cell. 2011;146:247-61 pubmed publisher
    ..In addition, they provide insight into the molecular basis of the cognitive and allied defects in FXS and ASD and suggest multiple targets for clinical intervention...
  30. Zhang Y, Brown M, Hyland C, Chen Y, Kronengold J, Fleming M, et al. Regulation of neuronal excitability by interaction of fragile X mental retardation protein with slack potassium channels. J Neurosci. 2012;32:15318-27 pubmed publisher
    Loss of the RNA-binding protein fragile X mental retardation protein (FMRP) represents the most common form of inherited intellectual disability...
  31. Nahhas F, Monroe T, Prior T, Botma P, Fang J, Snyder P, et al. Evaluation of the human fragile X mental retardation 1 polymerase chain reaction reagents to amplify the FMR1 gene: testing in a clinical diagnostic laboratory. Genet Test Mol Biomarkers. 2012;16:187-92 pubmed publisher
    Fragile X syndrome (FXS) is caused by the absence of a functional fragile X mental retardation protein (FMRP)...
  32. Friedman S, Dani N, Rushton E, Broadie K. Fragile X mental retardation protein regulates trans-synaptic signaling in Drosophila. Dis Model Mech. 2013;6:1400-13 pubmed publisher
  33. Colak D, Zaninovic N, Cohen M, Rosenwaks Z, Yang W, Gerhardt J, et al. Promoter-bound trinucleotide repeat mRNA drives epigenetic silencing in fragile X syndrome. Science. 2014;343:1002-5 pubmed publisher
    ..Thus, our data link trinucleotide-repeat expansion to a form of RNA-directed gene silencing mediated by direct interactions of the trinucleotide-repeat RNA and DNA. ..
  34. Hunsaker M, von Leden R, Ta B, Goodrich Hunsaker N, Arqué G, Kim K, et al. Motor deficits on a ladder rung task in male and female adolescent and adult CGG knock-in mice. Behav Brain Res. 2011;222:117-21 pubmed publisher
    ..The results demonstrate that both male and female CGG KI mice showed a greater number of foot slips as a function of increased CGG repeat length, independent of the age of the animal or general activity level. ..
  35. Callan M, Zarnescu D. Heads-up: new roles for the fragile X mental retardation protein in neural stem and progenitor cells. Genesis. 2011;49:424-40 pubmed publisher
    ..is the most common form of inherited mental retardation and is caused by the loss of function for Fragile X Mental Retardation Protein (FMRP), a selective RNA-binding protein with a demonstrated role in the localized translation of ..
  36. Michalon A, Sidorov M, Ballard T, Ozmen L, Spooren W, Wettstein J, et al. Chronic pharmacological mGlu5 inhibition corrects fragile X in adult mice. Neuron. 2012;74:49-56 pubmed publisher
    ..It is of great interest how these findings may translate into ongoing clinical research testing mGlu5 inhibitors in FXS patients. ..
  37. Gleicher N, Weghofer A, Kim A, Barad D. The impact in older women of ovarian FMR1 genotypes and sub-genotypes on ovarian reserve. PLoS ONE. 2012;7:e33638 pubmed publisher
    ..Known associated with low FOR at young age, het-norm/high, thus, appears to preserve FOR into older age, and both het sub-genotypes appear to expand female reproductive lifespan into opposite directions. ..
  38. Niere F, Wilkerson J, Huber K. Evidence for a fragile X mental retardation protein-mediated translational switch in metabotropic glutamate receptor-triggered Arc translation and long-term depression. J Neurosci. 2012;32:5924-36 pubmed publisher
    ..Fmr1 encodes fragile X mental retardation protein (FMRP), a dendritic RNA binding protein that functions, in part, as a translational suppressor...
  39. Datta S, Alam M, Majumdar S, Mehta A, Maiti S, Wadhwa N, et al. Nucleosomal occupancy and CGG repeat expansion: a comparative analysis of triplet repeat region from mouse and human fragile X mental retardation gene 1. Chromosome Res. 2011;19:445-55 pubmed publisher
    ..Our studies demonstrate that flanking DNA sequences can influence repeat instability through modulation of nucleosome occupancy in the region...
  40. Willemsen R, Levenga J, Oostra B. CGG repeat in the FMR1 gene: size matters. Clin Genet. 2011;80:214-25 pubmed publisher
    ..The pathogenic mechanisms thought to underlie these disorders are discussed. This review gives insight on the implications of all possible repeat length categories seen in fragile X families...
  41. Muddashetty R, Nalavadi V, Gross C, Yao X, Xing L, Laur O, et al. Reversible inhibition of PSD-95 mRNA translation by miR-125a, FMRP phosphorylation, and mGluR signaling. Mol Cell. 2011;42:673-88 pubmed publisher
    ..These findings reveal a mechanism whereby FMRP phosphorylation provides a reversible switch for AGO2 and microRNA to selectively regulate mRNA translation at synapses in response to receptor activation. ..
  42. Gleicher N, Weghofer A, Lee I, Barad D. Association of FMR1 genotypes with in vitro fertilization (IVF) outcomes based on ethnicity/race. PLoS ONE. 2011;6:e18781 pubmed publisher
    ..5-times the odds of being associated with autoimmune positivity (OR 2.5, 1.34-4.55; P?=?0.004). FMR1 genotypes offer a possible explanation for differences in IVF outcomes between races/ethnicities. ..
  43. Gatto C, Broadie K. Fragile X mental retardation protein is required for programmed cell death and clearance of developmentally-transient peptidergic neurons. Dev Biol. 2011;356:291-307 pubmed publisher
    ..The novel defect of impaired apoptosis and aberrant neuron persistence in the Drosophila FXS model suggests an entirely new level of "pruning" dysfunction may contribute to the FXS disease state. ..
  44. Pirozzi F, Tabolacci E, Neri G. The FRAXopathies: definition, overview, and update. Am J Med Genet A. 2011;155A:1803-16 pubmed publisher
    ..The understanding of these mechanisms is already generating promising therapeutic approaches...
  45. Tessier C, Broadie K. Molecular and genetic analysis of the Drosophila model of fragile X syndrome. Results Probl Cell Differ. 2012;54:119-56 pubmed publisher
    ..In turn, we consider FMR1 mechanistic relationships in non-neuronal tissues (germ cells and embryos), peripheral motor and sensory circuits, and central brain circuits involved in circadian clock activity and learning/memory...
  46. Fatemi S, Folsom T, Kneeland R, Liesch S. Metabotropic glutamate receptor 5 upregulation in children with autism is associated with underexpression of both Fragile X mental retardation protein and GABAA receptor beta 3 in adults with autism. Anat Rec (Hoboken). 2011;294:1635-45 pubmed publisher
    ..In animal models, altered expression of Fragile X mental retardation protein (FMRP) has been linked to downregulation of GABA receptors...
  47. Karimov C, Moragianni V, Cronister A, Srouji S, Petrozza J, Racowsky C, et al. Increased frequency of occult fragile X-associated primary ovarian insufficiency in infertile women with evidence of impaired ovarian function. Hum Reprod. 2011;26:2077-83 pubmed publisher
    ..Although the FMR1 repeat lengths were longer in women with occult POI, the data do not support the use of a repeat length cutoff to predict occult POI. ..
  48. Hunsaker M, Greco C, Spath M, Smits A, Navarro C, Tassone F, et al. Widespread non-central nervous system organ pathology in fragile X premutation carriers with fragile X-associated tremor/ataxia syndrome and CGG knock-in mice. Acta Neuropathol. 2011;122:467-79 pubmed publisher
  49. Yang Q, Feng B, Zhang K, Guo Y, Liu S, Wu Y, et al. Excessive astrocyte-derived neurotrophin-3 contributes to the abnormal neuronal dendritic development in a mouse model of fragile X syndrome. PLoS Genet. 2012;8:e1003172 pubmed publisher
    ..This study indicates that excessive NT-3 from astrocytes contributes to the abnormal neuronal dendritic development and that astrocytes could be a potential therapeutic target for FXS. ..
  50. Ascano M, Mukherjee N, Bandaru P, Miller J, Nusbaum J, Corcoran D, et al. FMRP targets distinct mRNA sequence elements to regulate protein expression. Nature. 2012;492:382-6 pubmed publisher
    ..As the importance of signalling pathways in both FXS and ASD is becoming increasingly apparent, our results provide a ranked list of genes as basis for the pursuit of new therapeutic targets for these neurological disorders. ..
  51. Bhogal B, Jepson J, Savva Y, Pepper A, Reenan R, Jongens T. Modulation of dADAR-dependent RNA editing by the Drosophila fragile X mental retardation protein. Nat Neurosci. 2011;14:1517-24 pubmed publisher
    ..These results link dFMR1 with the RNA-editing pathway and suggest that proper NMJ synaptic architecture requires modulation of dADAR activity by dFMR1. ..
  52. Coffee R, Williamson A, Adkins C, Gray M, Page T, Broadie K. In vivo neuronal function of the fragile X mental retardation protein is regulated by phosphorylation. Hum Mol Genet. 2012;21:900-15 pubmed publisher
    ..We conclude that human FMRP S500 phosphorylation is necessary for its in vivo function as a neuronal translational repressor and regulator of synaptic architecture, and for the manifestation of FMRP-dependent learning behavior. ..
  53. Goebel Goody S, Wilson Wallis E, Royston S, Tagliatela S, Naegele J, Lombroso P. Genetic manipulation of STEP reverses behavioral abnormalities in a fragile X syndrome mouse model. Genes Brain Behav. 2012;11:586-600 pubmed publisher
    ..autism, is caused by an expansion in the Fmr1 gene that prevents transcription and translation of fragile X mental retardation protein (FMRP)...