From FMRP function to potential therapies for fragile X syndrome

Neurochemical Research

Volumn 39, Issue 6, 2014, Pages 1016-1031

  Sethna, Ferzin ^a   Moon, Changjong ^b   Wang, Hongbing ^a  

^a MICHIGAN STATE UNIVERSITY   (United States)

^b Chonnam National University   (South Korea)

Author keywords

FMR1; FMRP; Fragile X syndrome; Gq coupled receptors; LTD; LTP; Mouse model; RNA binding protein; Therapeutic development; Translation

Indexed keywords

FRAGILE X MENTAL RETARDATION 1; FRAGILE X MENTAL RETARDATION PROTEIN; MESSENGER RNA; METABOTROPIC RECEPTOR; UNCLASSIFIED DRUG; UNTRANSLATED RNA; FMR1 PROTEIN, HUMAN; MINOCYCLINE;

CONTROLLED CLINICAL TRIAL (TOPIC); FRAGILE X SYNDROME; GENE FUNCTION; GENE TARGETING; HUMAN; INTRACELLULAR SIGNALING; NERVE CELL PLASTICITY; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN PROCESSING; PROTEIN SYNTHESIS; REVIEW; RNA BINDING; RNA METABOLISM; ANIMAL; DRUG DELIVERY SYSTEM; DRUG EFFECTS; GENETICS; PHYSIOLOGY; PROCEDURES;

ANIMALS; DRUG DELIVERY SYSTEMS; FRAGILE X MENTAL RETARDATION PROTEIN; FRAGILE X SYNDROME; HUMANS; MINOCYCLINE; PROTEIN BIOSYNTHESIS;

EID: 84901471786     PISSN: 03643190     EISSN: 15736903     Source Type: Journal    
DOI: 10.1007/s11064-013-1229-3     Document Type: Review

References (181)

1. Santoro MR, Bray SM, Warren ST (2012) Molecular mechanisms of fragile X syndrome: a twenty-year perspective. Annu Rev Pathol 7:219-245
2. Bagni C, Tassone F, Neri G, Hagerman R (2012) Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics. J Clin Invest 122(12):4314-4322
3. Krawczun MS, Jenkins EC, Brown WT (1985) Analysis of the fragile-X chromosome: localization and detection of the fragile site in high resolution preparations. Hum Genet 69(3):209-211 (Pubitemid 15142096)
4. Verkerk AJ, Pieretti M, Sutcliffe JS, Fu YH, Kuhl DP, Pizzuti A, Reiner O, Richards S, Victoria MF, Zhang FP et al (1991) Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 65(5):905-914 (Pubitemid 121001321)
5. Peprah E (2012) Fragile X syndrome: the FMR1 CGG repeat distribution among world populations. Ann Hum Genet 76(2): 178-191
6. Maddalena A, Richards CS, McGinniss MJ, Brothman A, Desnick RJ, Grier RE, Hirsch B, Jacky P, McDowell GA, Popovich B, Watson M, Wolff DJ (2001) Technical standards and guidelines for fragile X: the first of a series of disease-specific supplements to the Standards and Guidelines for Clinical Genetics Laboratories of the American College of Medical Genetics. Quality Assurance Subcommittee of the Laboratory Practice Committee. Genet Med 3(3):200-205
7. De Boulle K, Verkerk AJ, Reyniers E, Vits L, Hendrickx J, Van Roy B, Van den Bos F, de Graaff E, Oostra BA, Willems PJI (1993) A point mutation in the FMR-1 gene associated with fragile X mental retardation. Nat Genet 3(1):31-35 (Pubitemid 23063285)
8. Coffee B, Ikeda M, Budimirovic DB, Hjelm LN, Kaufmann WE, Warren ST (2008) Mosaic FMR1 deletion causes fragile X syndrome and can lead to molecular misdiagnosis: a case report and review of the literature. Am J Med Genet A 146A(10):1358-1367 (Pubitemid 351631339)
9. Collins SC, Bray SM, Suhl JA, Cutler DJ, Coffee B, Zwick ME, Warren ST (2010) Identification of novel FMR1 variants by massively parallel sequencing in developmentally delayed males. Am J Med Genet A 152A(10):2512-2520
10. Pieretti M, Zhang FP, Fu YH, Warren ST, Oostra BA, Caskey CT, Nelson DL (1991) Absence of expression of the FMR-1 gene in fragile X syndrome. Cell 66(4):817-822 (Pubitemid 121001715)
11. Sutcliffe JS, Nelson DL, Zhang F, Pieretti M, Caskey CT, Saxe D, Warren ST (1992) DNA methylation represses FMR-1 transcription in fragile X syndrome. Hum Mol Genet 1(6):397-400
12. Pietrobono R, Tabolacci E, Zalfa F, Zito I, Terracciano A, Moscato U, Bagni C, Oostra B, Chiurazzi P, Neri G (2005) Molecular dissection of the events leading to inactivation of the FMR1 gene. Hum Mol Genet 14(2):267-277
13. Tassone F, Hagerman RJ, Loesch DZ, Lachiewicz A, Taylor AK, Hagerman PJ (2000) Fragile X males with unmethylated, full mutation trinucleotide repeat expansions have elevated levels of FMR1 messenger RNA. Am J Med Genet 94(3): 232-236
14. Tabolacci E, Moscato U, Zalfa F, Bagni C, Chiurazzi P, Neri G (2008) Epigenetic analysis reveals a euchromatic configuration in the FMR1 unmethylated full mutations. Eur J Hum Genet 16(12):1487-1498
15. Dobson T, Kube E, Timmerman S, Krushel LA (2008) Identifying intrinsic and extrinsic determinants that regulate internal initiation of translation mediated by the FMR1 50 leader. BMC Mol Biol 9:89
16. Coffee B, Zhang F, Ceman S, Warren ST, Reines D (2002) Histone modifications depict an aberrantly heterochromatinized FMR1 gene in fragile x syndrome. Am J Hum Genet 71(4): 923-932 (Pubitemid 135750522)
17. Eiges R, Urbach A, Malcov M, Frumkin T, Schwartz T, Amit A, Yaron Y, Eden A, Yanuka O, Benvenisty N, Ben-Yosef D (2007) Developmental study of fragile X syndrome using human embryonic stem cells derived from preimplantation genetically diagnosed embryos. Cell Stem Cell 1(5):568-577 (Pubitemid 350079966)
18. The Dutch-Belgian Fragile X Consortium (1994) Fmr1 knockout mice: a model to study fragile X mental retardation. Cell 78(1):23-33
19. Morales J, Hiesinger PR, Schroeder AJ, Kume K, Verstreken P, Jackson FR, Nelson DL, Hassan BA (2002) Drosophila fragile X protein, DFXR, regulates neuronal morphology and function in the brain. Neuron 34(6):961-972 (Pubitemid 34722285)
20. Zhang YQ, Bailey AM, Matthies HJ, Renden RB, Smith MA, Speese SD, Rubin GM, Broadie K (2001) Drosophila fragile X-related gene regulates the MAP1B homolog Futsch to control synaptic structure and function. Cell 107(5):591-603 (Pubitemid 34014861)
21. den Broeder MJ, van der Linde H, Brouwer JR, Oostra BA, Willemsen R, Ketting RF (2009) Generation and characterization of FMR1 knockout zebrafish. PLoS ONE 4(11):e7910
22. Zang JB,NosyrevaED, SpencerCM, Volk LJ,MusunuruK, Zhong R, Stone EF, Yuva-Paylor LA, Huber KM, Paylor R, Darnell JC, Darnell RB (2009) A mouse model of the human Fragile X syndrome I304N mutation. PLoS Genet 5(12):e1000758
23. Brouwer JR, Mientjes EJ, Bakker CE, Nieuwenhuizen IM, Severijnen LA, Van der Linde HC, Nelson DL, Oostra BA, Willemsen R (2007) Elevated Fmr1 mRNA levels and reduced protein expression in a mouse model with an unmethylated Fragile X full mutation. Exp Cell Res 313(2):244-253 (Pubitemid 46048813)
24. Chiurazzi P, Pomponi MG, Willemsen R, Oostra BA, Neri G (1998) In vitro reactivation of the FMR1 gene involved in fragile X syndrome. Hum Mol Genet 7(1):109-113 (Pubitemid 28040744)
25. Chiurazzi P, Pomponi MG, Pietrobono R, Bakker CE, Neri G, Oostra BA (1999) Synergistic effect of histone hyperacetylation and DNA demethylation in the reactivation of the FMR1 gene. Hum Mol Genet 8(12):2317-2323 (Pubitemid 29525348)
26. Baker KB, Wray SP, Ritter R, Mason S, Lanthorn TH, Savelieva KV (2010) Male and female Fmr1 knockout mice on C57 albino background exhibit spatial learning and memory impairments. Genes Brain Behav 9(6):562-574
27. Dobkin C, Rabe A, Dumas R, El Idrissi A, Haubenstock H, Brown WT (2000) Fmr1 knockout mouse has a distinctive strain-specific learning impairment. Neuroscience 100(2):423-429
28. Paradee W, Melikian HE, Rasmussen DL, Kenneson A, Conn PJ, Warren ST (1999) Fragile X mouse: strain effects of knockout phenotype and evidence suggesting deficient amygdala function. Neuroscience 94(1):185-192 (Pubitemid 29457608)
29. Qin M, Kang J, Smith CB (2005) A null mutation for Fmr1 in female mice: effects on regional cerebral metabolic rate for glucose and relationship to behavior. Neuroscience 135(3):999-1009 (Pubitemid 41407761)
30. Qin M, Kang J, Smith CB (2002) Increased rates of cerebral glucose metabolism in a mouse model of fragile X mental retardation. Proc Natl Acad Sci USA 99(24):15758-15763 (Pubitemid 35404003)
31. Dolen G, Osterweil E, Rao BS, Smith GB, Auerbach BD, Chattarji S, Bear MF (2007) Correction of fragile X syndrome in mice. Neuron 56(6):955-962 (Pubitemid 350251119)
32. Van Dam D, D'Hooge R, Hauben E, Reyniers E, Gantois I, Bakker CE, Oostra BA, Kooy RF, De Deyn PP (2000) Spatial learning, contextual fear conditioning and conditioned emotional response in Fmr1 knockout mice. Behav Brain Res 117(1-2):127-136
33. Bhattacharya A, Kaphzan H, Alvarez-Dieppa AC, Murphy JP, Pierre P, Klann E (2012) Genetic removal of p70 S6 kinase 1 corrects molecular, synaptic, and behavioral phenotypes in fragile X syndrome mice. Neuron 76(2):325-337
34. Ventura R, Pascucci T, Catania MV, Musumeci SA, Puglisi-Allegra S (2004) Object recognition impairment in Fmr1 knockout mice is reversed by amphetamine: involvement of dopamine in the medial prefrontal cortex. Behav Pharmacol 15(5-6):433-442 (Pubitemid 39238357)
35. Chen L, Toth M (2001) Fragile X mice develop sensory hyperreactivity to auditory stimuli. Neuroscience 103(4):1043-1050 (Pubitemid 32289314)
36. Musumeci SA, Bosco P, Calabrese G, Bakker C, De Sarro GB, Elia M, Ferri R, Oostra BA (2000) Audiogenic seizures susceptibility in transgenic mice with fragile X syndrome. Epilepsia 41(1):19-23 (Pubitemid 30036849)
37. Qiu LF, Lu TJ, Hu XL, Yi YH, Liao WP, Xiong ZQ (2009) Limbic epileptogenesis in a mouse model of fragile X syndrome. Cereb Cortex 19(7):1504-1514
38. Chuang SC, Zhao W, Bauchwitz R, Yan Q, Bianchi R, Wong RK (2005) Prolonged epileptiform discharges induced by altered group I metabotropic glutamate receptor-mediated synaptic responses in hippocampal slices of a fragile X mouse model. J Neurosci 25(35):8048-8055 (Pubitemid 41254408)
39. Yan QJ, Rammal M, Tranfaglia M, Bauchwitz RP (2005) Suppression of two major Fragile X Syndrome mouse model phenotypes by the mGluR5 antagonist MPEP. Neuropharmacology 49(7):1053-1066 (Pubitemid 41503304)
40. Spencer CM, Alekseyenko O, Serysheva E, Yuva-Paylor LA, Paylor R (2005) Altered anxiety-related and social behaviors in the Fmr1 knockout mouse model of fragile X syndrome. Genes Brain Behav 4(7):420-430 (Pubitemid 41428518)
41. Bilousova TV, Dansie L, Ngo M, Aye J, Charles JR, Ethell DW, Ethell IM (2009) Minocycline promotes dendritic spine maturation and improves behavioural performance in the fragile X mouse model. J Med Genet 46(2):94-102
42. Nielsen DM, Derber WJ, McClellan DA, Crnic LS (2002) Alterations in the auditory startle response in Fmr1 targeted mutant mouse models of fragile X syndrome. Brain Res 927(1):8-17 (Pubitemid 34114044)
43. Liu ZH, Chuang DM, Smith CB (2011) Lithium ameliorates phenotypic deficits in a mouse model of fragile X syndrome. Int J Neuropsychopharmacol 14(5):618-630
44. Errijgers V, Fransen E, D'Hooge R, De Deyn PP, Kooy RF (2008) Effect of genetic background on acoustic startle response in fragile X knockout mice. Genet Res (Camb) 90(4):341-345
45. Thomas AM, Bui N, Graham D, Perkins JR, Yuva-Paylor LA, Paylor R (2011) Genetic reduction of group 1 metabotropic glutamate receptors alters select behaviors in a mouse model for fragile X syndrome. Behav Brain Res 223(2):310-321
46. Pietropaolo S, Guilleminot A, Martin B, D'Amato FR, Crusio WE (2011) Genetic-background modulation of core and variable autistic-like symptoms in Fmr1 knock-out mice. PLoS ONE 6(2):e17073
47. Frankland PW, Wang Y, Rosner B, Shimizu T, Balleine BW, Dykens EM, Ornitz EM, Silva AJ (2004) Sensorimotor gating abnormalities in young males with fragile X syndrome and Fmr1-knockout mice. Mol Psychiatry 9(4):417-425 (Pubitemid 38534702)
48. Levenga J, Hayashi S, de Vrij FM, Koekkoek SK, van der Linde HC, Nieuwenhuizen I, Song C, Buijsen RA, Pop AS, Gomezmancilla B, Nelson DL, Willemsen R, Gasparini F, Oostra BA (2011) AFQ056, a new mGluR5 antagonist for treatment of fragile X syndrome. Neurobiol Dis 42(3):311-317
49. de Vrij FM, Levenga J, van der Linde HC, Koekkoek SK, De Zeeuw CI, Nelson DL, Oostra BA, Willemsen R (2008) Rescue of behavioral phenotype and neuronal protrusion morphology in Fmr1 KO mice. Neurobiol Dis 31(1):127-132 (Pubitemid 351822560)
50. Goebel-Goody SM, Wilson-Wallis ED, Royston S, Tagliatela SM, Naegele JR, Lombroso PJ (2012) Genetic manipulation of STEP reverses behavioral abnormalities in a fragile X syndrome mouse model. Genes Brain Behav 11(5):586-600
51. Mines MA, Yuskaitis CJ, King MK, Beurel E, Jope RS (2010) GSK3 influences social preference and anxiety-related behaviors during social interaction in a mouse model of fragile X syndrome and autism. PLoS ONE 5(3):e9706
52. Wohr M, Scattoni ML (2013) Behavioural methods used in rodent models of autism spectrum disorders: current standards and new developments. Behav Brain Res 251:5-17
53. Thomas A, Burant A, Bui N, Graham D, Yuva-Paylor LA, Paylor R (2009) Marble burying reflects a repetitive and perseverative behavior more than novelty-induced anxiety. Psychopharmacology 204(2):361-373
54. Thomas AM, Bui N, Perkins JR, Yuva-Paylor LA, Paylor R (2012) Group I metabotropic glutamate receptor antagonists alter select behaviors in a mouse model for fragile X syndrome. Psychopharmacology 219(1):47-58
55. Roy S, Watkins N, Heck D (2012) Comprehensive analysis of ultrasonic vocalizations in a mouse model of fragile X syndrome reveals limited, call type specific deficits. PLoS ONE 7(9): e44816
56. Rotschafer SE, Trujillo MS, Dansie LE, Ethell IM, Razak KA (2012) Minocycline treatment reverses ultrasonic vocalization production deficit in a mouse model of Fragile X Syndrome. Brain Res 1439:7-14
57. Irwin SA, Patel B, Idupulapati M, Harris JB, Crisostomo RA, Larsen BP, Kooy F, Willems PJ, Cras P, Kozlowski PB, Swain RA, Weiler IJ, Greenough WT (2001) Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with fragile-X syndrome: a quantitative examination. Am J Med Genet 98(2):161-167 (Pubitemid 32051804)
58. Grossman AW, Aldridge GM, Weiler IJ, Greenough WT (2006) Local protein synthesis and spine morphogenesis: fragile X syndrome and beyond. J Neurosci 26(27):7151-7155
59. Hayashi ML, Rao BS, Seo JS, Choi HS, Dolan BM, Choi SY, Chattarji S, Tonegawa S (2007) Inhibition of p21-activated kinase rescues symptoms of fragile X syndrome in mice. Proc Natl Acad Sci USA 104(27):11489-11494 (Pubitemid 47175167)
60. Wan L, Dockendorff TC, Jongens TA, Dreyfuss G (2000) Characterization of dFMR1, a Drosophila melanogaster homolog of the fragile X mental retardation protein. Mol Cell Biol 20(22):8536-8547
61. Dockendorff TC, Su HS, McBride SM, Yang Z, Choi CH, Siwicki KK, Sehgal A, Jongens TA (2002) Drosophila lacking dfmr1 activity show defects in circadian output and fail to maintain courtship interest. Neuron 34(6):973-984 (Pubitemid 34722286)
62. McBride SM, Choi CH, Wang Y, Liebelt D, Braunstein E, Ferreiro D, Sehgal A, Siwicki KK, Dockendorff TC, Nguyen HT, McDonald TV, Jongens TA (2005) Pharmacological rescue of synaptic plasticity, courtship behavior, and mushroom body defects in a Drosophila model of fragile X syndrome. Neuron 45(5):753-764 (Pubitemid 40320709)
63. Chang S, Bray SM, Li Z, Zarnescu DC, He C, Jin P, Warren ST (2008) Identification of small molecules rescuing fragile X syndrome phenotypes in Drosophila. Nat Chem Biol 4(4): 256-263 (Pubitemid 351419125)
64. Yun SW, Platholi J, Flaherty MS, Fu W, Kottmann AH, Toth M (2006) Fmrp is required for the establishment of the startle response during the critical period of auditory development. Brain Res 1110(1):159-165 (Pubitemid 44349143)
65. Qin M, Xia Z, Huang T, Smith CB (2011) Effects of chronic immobilization stress on anxiety-like behavior and basolateral amygdala morphology in Fmr1 knockout mice. Neuroscience 194:282-290
66. Berry-Kravis E, Sumis A, Hervey C, Nelson M, Porges SW, Weng N, Weiler IJ, Greenough WT (2008) Open-label treatment trial of lithium to target the underlying defect in fragile X syndrome. J Dev Behav Pediatr 29(4):293-302
67. Jacquemont S, Curie A, des Portes V, Torrioli MG, Berry-Kravis E, Hagerman RJ, Ramos FJ, Cornish K, He Y, Paulding C, Neri G, Chen F, Hadjikhani N, Martinet D, Meyer J, Beckmann JS, Delange K, Brun A, Bussy G, Gasparini F, Hilse T, Floesser A, Branson J, Bilbe G, Johns D, Gomez-Mancilla B (2011) Epigenetic modification of the FMR1 gene in fragile X syndrome is associated with differential response to the mGluR5 antagonist AFQ056. Sci Transl Med 3(64):64ra61
68. Weiler IJ, Irwin SA, Klintsova AY, Spencer CM, Brazelton AD, Miyashiro K, Comery TA, Patel B, Eberwine J, Greenough WT (1997) Fragile X mental retardation protein is translated near synapses in response to neurotransmitter activation. Proc Natl Acad Sci USA 94(10):5395-5400 (Pubitemid 27214794)
69. Siomi H, Choi M, Siomi MC, Nussbaum RL, Dreyfuss G (1994) Essential role for KH domains in RNA binding: impaired RNA binding by a mutation in the KH domain of FMR1 that causes fragile X syndrome. Cell 77(1):33-39 (Pubitemid 24184685)
70. Siomi H, Siomi MC, Nussbaum RL, Dreyfuss G (1993) The protein product of the fragile X gene, FMR1, has characteristics of an RNA-binding protein. Cell 74(2):291-298 (Pubitemid 23221705)
71. Corbin F, Bouillon M, Fortin A, Morin S, Rousseau F, Khandjian EW (1997) The fragile X mental retardation protein is associated with poly(A)? mRNA in actively translating polyribosomes. Hum Mol Genet 6(9):1465-1472 (Pubitemid 27397022)
72. Feng Y, Absher D, Eberhart DE, Brown V, Malter HE, Warren ST (1997) FMRP associates with polyribosomes as an mRNP, and the I304N mutation of severe fragile X syndrome abolishes this association. Mol Cell 1(1):109-118 (Pubitemid 127376398)
73. Feng Y, Gutekunst CA, Eberhart DE, Yi H, Warren ST, Hersch SM (1997) Fragile X mental retardation protein: nucleocytoplasmic shuttling and association with somatodendritic ribosomes. J Neurosci 17(5):1539-1547 (Pubitemid 27089800)
74. Darnell JC, Fraser CE, Mostovetsky O, Stefani G, Jones TA, Eddy SR, Darnell RB (2005) Kissing complex RNAs mediate interaction between the Fragile-X mental retardation protein KH2 domain and brain polyribosomes. Genes Dev 19(8):903-918 (Pubitemid 40548059)
75. Darnell JC, Jensen KB, Jin P, Brown V, Warren ST, Darnell RB (2001) Fragile X mental retardation protein targets G quartet mRNAs important for neuronal function. Cell 107(4):489-499 (Pubitemid 33152784)
76. Bechara EG, Didiot MC, Melko M, Davidovic L, Bensaid M, Martin P, Castets M, Pognonec P, Khandjian EW, Moine H, Bardoni B (2009) A novel function for fragile X mental retardation protein in translational activation. PLoS Biol 7(1):e16
77. Eberhart DE, Malter HE, Feng Y, Warren ST (1996) The fragile X mental retardation protein is a ribonucleoprotein containing both nuclear localization and nuclear export signals. Hum Mol Genet 5(8):1083-1091 (Pubitemid 26318545)
78. Napoli I, Mercaldo V, Boyl PP, Eleuteri B, Zalfa F, De Rubeis S, Di Marino D, Mohr E, Massimi M, Falconi M, Witke W, Costa-Mattioli M, Sonenberg N, Achsel T, Bagni C (2008) The fragile X syndrome protein represses activity-dependent translation through CYFIP1, a new 4E-BP. Cell 134(6):1042-1054
79. Jin P, Zarnescu DC, Ceman S, Nakamoto M, Mowrey J, Jongens TA, Nelson DL, Moses K, Warren ST (2004) Biochemical and genetic interaction between the fragile X mental retardation protein and the microRNA pathway. Nat Neurosci 7(2):113-117 (Pubitemid 38129786)
80. Plante I, Davidovic L, Ouellet DL, Gobeil LA, Tremblay S, Khandjian EW, Provost P (2006) Dicer-derived microRNAs are utilized by the fragile X mental retardation protein for assembly on target RNAs. J Biomed Biotechnol 4:64347
81. Brown V, Jin P, Ceman S, Darnell JC, O'Donnell WT, Tenenbaum SA, Jin X, Feng Y, Wilkinson KD, Keene JD, Darnell RB, Warren ST (2001) Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome. Cell 107(4):477-487 (Pubitemid 33152783)
82. Darnell JC, Van Driesche SJ, Zhang C, Hung KY, Mele A, Fraser CE, Stone EF, Chen C, Fak JJ, Chi SW, Licatalosi DD, Richter JD, Darnell RB (2011) FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism. Cell 146(2):247-261
83. Ascano M Jr, Mukherjee N, Bandaru P, Miller JB, Nusbaum JD, Corcoran DL, Langlois C, Munschauer M, Dewell S, Hafner M, Williams Z, Ohler U, Tuschl T (2012) FMRP targets distinct mRNA sequence elements to regulate protein expression. Nature 492(7429):382-386
84. Edbauer D, Neilson JR, Foster KA, Wang CF, Seeburg DP, Batterton MN, Tada T, Dolan BM, Sharp PA, Sheng M (2010) Regulation of synaptic structure and function by FMRP-associated microRNAs miR-125b and miR-132. Neuron 65(3):373-384
85. Muddashetty RS, Nalavadi VC, Gross C, Yao X, Xing L, Laur O, Warren ST, Bassell GJ (2011) Reversible inhibition of PSD-95 mRNA translation by miR-125a, FMRP phosphorylation, and mGluR signaling. Mol Cell 42(5):673-688
86. Dictenberg JB, Swanger SA, Antar LN, Singer RH, Bassell GJ (2008) A direct role for FMRP in activity-dependent dendritic mRNA transport links filopodial-spine morphogenesis to fragile X syndrome. Dev Cell 14(6):926-939 (Pubitemid 351757204)
87. Zalfa F, Eleuteri B, Dickson KS, Mercaldo V, De Rubeis S, di Penta A, Tabolacci E, Chiurazzi P, Neri G, Grant SG, Bagni C (2007) A new function for the fragile X mental retardation protein in regulation of PSD-95 mRNA stability. Nat Neurosci 10(5):578-587 (Pubitemid 46652449)
88. Lu R, Wang H, Liang Z, Ku L, O'Donnell WT, Li W, Warren ST, Feng Y (2004) The fragile X protein controls microtubule-associated protein 1B translation and microtubule stability in brain neuron development. Proc Natl Acad Sci USA 101(42):15201-15206 (Pubitemid 39391742)
89. Osterweil EK, Krueger DD, Reinhold K, Bear MF (2010) Hypersensitivity to mGluR5 and ERK1/2 leads to excessive protein synthesis in the hippocampus of a mouse model of fragile X syndrome. J Neurosci 30(46):15616-15627
90. Gross C, Nakamoto M, Yao X, Chan CB, Yim SY, Ye K, Warren ST, Bassell GJ (2010) Excess phosphoinositide 3-kinase subunit synthesis and activity as a novel therapeutic target in fragile X syndrome. J Neurosci 30(32):10624-10638
91. Todd PK, Mack KJ, Malter JS (2003) The fragile X mental retardation protein is required for type-I metabotropic glutamate receptor-dependent translation of PSD-95. Proc Natl Acad Sci USA 100(24):14374-14378 (Pubitemid 37499244)
92. Hou L, Antion MD, Hu D, Spencer CM, Paylor R, Klann E (2006) Dynamic translational and proteasomal regulation of fragile X mental retardation protein controls mGluR-dependent long-term depression. Neuron 51(4):441-454 (Pubitemid 44189802)
93. Lee HY, Ge WP, Huang W, He Y, Wang GX, Rowson-Baldwin A, Smith SJ, Jan YN, Jan LY (2011) Bidirectional regulation of dendritic voltage-gated potassium channels by the fragile X mental retardation protein. Neuron 72(4):630-642
94. Weiler IJ, Spangler CC, Klintsova AY, Grossman AW, Kim SH, Bertaina-Anglade V, Khaliq H, de Vries FE, Lambers FA, Hatia F, Base CK, Greenough WT (2004) Fragile X mental retardation protein is necessary for neurotransmitter-activated protein translation at synapses. Proc Natl Acad Sci USA 101(50): 17504-17509 (Pubitemid 39657433)
95. Bear MF, Huber KM, Warren ST (2004) The mGluR theory of fragile X mental retardation. Trends Neurosci 27(7):370-377 (Pubitemid 38829251)
96. Lauterborn JC, Rex CS, Kramar E, Chen LY, Pandyarajan V, Lynch G, Gall CM (2007) Brain-derived neurotrophic factor rescues synaptic plasticity in a mouse model of fragile X syndrome. J Neurosci 27(40):10685-10694 (Pubitemid 47535868)
97. Huber KM, Gallagher SM, Warren ST, Bear MF (2002) Altered synaptic plasticity in a mouse model of fragile X mental retardation. Proc Natl Acad Sci USA 99(11):7746-7750 (Pubitemid 34568762)
98. Niere F, Wilkerson JR, Huber KM (2012) Evidence for a fragile X mental retardation protein-mediated translational switch in metabotropic glutamate receptor-triggered Arc translation and long-term depression. J Neurosci 32(17):5924-5936
99. Nalavadi VC, Muddashetty RS, Gross C, Bassell GJ (2012) Dephosphorylation-induced ubiquitination and degradation of FMRP in dendrites: a role in immediate early mGluR-stimulated translation. J Neurosci 32(8):2582-2587
100. Waung MW, Pfeiffer BE, Nosyreva ED, Ronesi JA, Huber KM (2008) Rapid translation of Arc/Arg3.1 selectively mediates mGluR-dependent LTD through persistent increases in AMPAR endocytosis rate. Neuron 59(1):84-97 (Pubitemid 351905854)
101. Nakamoto M, Nalavadi V, Epstein MP, Narayanan U, Bassell GJ, Warren ST (2007) Fragile X mental retardation protein deficiency leads to excessive mGluR5-dependent internalization of AMPA receptors. Proc Natl Acad Sci USA 104(39): 15537-15542 (Pubitemid 47502952)
102. Vanderklish PW, Edelman GM (2002) Dendritic spines elongate after stimulation of group 1 metabotropic glutamate receptors in cultured hippocampal neurons. Proc Natl Acad Sci USA 99(3): 1639-1644 (Pubitemid 34136545)
103. Veloz MF, Buijsen R, Willemsen R, Cupido A, Bosman LW, Koekkoek SK, Potters JW, Oostra BA, De Zeeuw CI (2012) The effect of an mGluR5 inhibitor on procedural memory and avoidance discrimination impairments in Fmr1 KO mice. Genes Brain Behav 11(3):325-331
104. Berry-Kravis E, Hessl D, Coffey S, Hervey C, Schneider A, Yuhas J, Hutchison J, Snape M, Tranfaglia M, Nguyen DV, Hagerman R (2009) A pilot open label, single dose trial of fenobam in adults with fragile X syndrome. J Med Genet 46(4):266-271
105. Gantois I, Pop AS, de Esch CE, Buijsen RA, Pooters T, Gomez-Mancilla B, Gasparini F, Oostra BA, D'Hooge R, Willemsen R (2013) Chronic administration of AFQ056/Mavoglurant restores social behaviour in Fmr1 knockout mice. Behav Brain Res 239:72-79
106. Michalon A, Sidorov M, Ballard TM, Ozmen L, Spooren W, Wettstein JG, Jaeschke G, Bear MF, Lindemann L (2012) Chronic pharmacological mGlu5 inhibition corrects fragile X in adult mice. Neuron 74(1):49-56
107. Volk LJ, Pfeiffer BE, Gibson JR, Huber KM (2007) Multiple Gq-coupled receptors converge on a common protein synthesisdependent long-term depression that is affected in fragile X syndrome mental retardation. J Neurosci 27(43):11624-11634 (Pubitemid 350006892)
108. Veeraragavan S, Bui N, Perkins JR, Yuva-Paylor LA, Carpenter RL, Paylor R (2011) Modulation of behavioral phenotypes by a muscarinic M1 antagonist in a mouse model of fragile X syndrome. Psychopharmacology 217(1):143-151
109. Veeraragavan S, Graham D, Bui N, Yuva-Paylor LA, Wess J, Paylor R (2012) Genetic reduction of muscarinic M4 receptor modulates analgesic response and acoustic startle response in a mouse model of fragile X syndrome (FXS). Behav Brain Res 228(1):1-8
110. Veeraragavan S, Bui N, Perkins JR, Yuva-Paylor LA, Paylor R (2011) The modulation of fragile X behaviors by the muscarinic M4 antagonist, tropicamide. Behav Neurosci 125(5):783-790
111. Wang H, Wu LJ, Kim SS, Lee FJ, Gong B, Toyoda H, Ren M, Shang YZ, Xu H, Liu F, Zhao MG, Zhuo M (2008) FMRP acts as a key messenger for dopamine modulation in the forebrain. Neuron 59(4):634-647
112. Costa L, Spatuzza M, D'Antoni S, Bonaccorso CM, Trovato C, Musumeci SA, Leopoldo M, Lacivita E, Catania MV, Ciranna L (2012) Activation of 5-HT7 serotonin receptors reverses metabotropic glutamate receptor-mediated synaptic plasticity in wild-type and Fmr1 knockout mice, a model of Fragile X syndrome. Biol Psychiatry 72(11):924-933
113. Wilson BM, Cox CL (2007) Absence of metabotropic glutamate receptor-mediated plasticity in the neocortex of fragile X mice. Proc Natl Acad Sci USA 104(7):2454-2459 (Pubitemid 46394340)
114. Suvrathan A, Hoeffer CA, Wong H, Klann E, Chattarji S (2010) Characterization and reversal of synaptic defects in the amygdala in a mouse model of fragile X syndrome. Proc Natl Acad Sci USA 107(25):11591-11596
115. Shang Y, Wang H, Mercaldo V, Li X, Chen T, Zhuo M (2009) Fragile X mental retardation protein is required for chemically-induced long-term potentiation of the hippocampus in adult mice. J Neurochem 111(3):635-646
116. Eadie BD, Cushman J, Kannangara TS, Fanselow MS, Christie BR (2012) NMDA receptor hypofunction in the dentate gyrus and impaired context discrimination in adult Fmr1 knockout mice. Hippocampus 22(2):241-254
117. Yun SH, Trommer BL (2011) Fragile X mice: reduced longterm potentiation and N-Methyl-D-Aspartate receptor-mediated neurotransmission in dentate gyrus. J Neurosci Res 89(2): 176-182
118. Christie SB, Akins MR, Schwob JE, Fallon JR (2009) The FXG: a presynaptic fragile X granule expressed in a subset of developing brain circuits. J Neurosci 29(5):1514-1524
119. Akins MR, Berk-Rauch HE, Fallon JR (2009) Presynaptic translation: stepping out of the postsynaptic shadow. Front Neural Circuits 3:17
120. Klemmer P, Meredith RM, Holmgren CD, Klychnikov OI, Stahl-Zeng J, Loos M, van der Schors RC, Wortel J, de Wit H, Spijker S, Rotaru DC, Mansvelder HD, Smit AB, Li KW (2011) Proteomics, ultrastructure, and physiology of hippocampal synapses in a fragile X syndrome mouse model reveal presynaptic phenotype. J Biol Chem 286(29):25495-25504
121. Deng PY, Sojka D, Klyachko VA (2011) Abnormal presynaptic short-term plasticity and information processing in a mouse model of fragile X syndrome. J Neurosci 31(30):10971-10982
122. Antar LN, Li C, Zhang H, Carroll RC, Bassell GJ (2006) Local functions for FMRP in axon growth cone motility and activity-dependent regulation of filopodia and spine synapses. Mol Cell Neurosci 32(1-2):37-48 (Pubitemid 43868095)
123. Deng PY, Rotman Z, Blundon JA, Cho Y, Cui J, Cavalli V, Zakharenko SS, Klyachko VA (2013) FMRP regulates neurotransmitter release and synaptic information transmission by modulating action potential duration via BK channels. Neuron 77(4):696-711
124. Brown MR, Kronengold J, Gazula VR, Chen Y, Strumbos JG, Sigworth FJ, Navaratnam D, Kaczmarek LK (2010) Fragile X mental retardation protein controls gating of the sodium-activated potassium channel Slack. Nat Neurosci 13(7):819-821
125. Park S, Park JM, Kim S, Kim JA, Shepherd JD, Smith-Hicks CL, Chowdhury S, Kaufmann W, Kuhl D, Ryazanov AG, Huganir RL, Linden DJ, Worley PF (2008) Elongation factor 2 and fragile X mental retardation protein control the dynamic translation of Arc/Arg3.1 essential for mGluR-LTD. Neuron 59(1):70-83 (Pubitemid 351905855)
126. Westmark CJ, Westmark PR, O'Riordan KJ, Ray BC, Hervey CM, Salamat MS, Abozeid SH, Stein KM, Stodola LA, Tranfaglia M, Burger C, Berry-Kravis EM, Malter JS (2011) Reversal of fragile X phenotypes by manipulation of AbetaPP/Abeta levels in Fmr1KO mice. PLoS ONE 6(10):e26549
127. Westmark CJ, Malter JS (2007) FMRP mediates mGluR5-dependent translation of amyloid precursor protein. PLoS Biol 5(3):e52
128. Korte M, Herrmann U, Zhang X, Draguhn A (2012) The role of APP and APLP for synaptic transmission, plasticity, and network function: lessons from genetic mouse models. Exp Brain Res 217(3-4):435-440
129. Westmark CJ, Westmark PR, Beard AM, Hildebrandt SM, Malter JS (2008) Seizure susceptibility and mortality in mice that over-express amyloid precursor protein. Int J Clin Exp Pathol 1(2):157-168
130. Malter JS, Ray BC, Westmark PR, Westmark CJ (2010) Fragile X syndrome and Alzheimer's disease: another story about APP and beta-amyloid. Curr Alzheimer Res 7(3):200-206
131. Wu J, Petralia RS, Kurushima H, Patel H, Jung MY, Volk L, Chowdhury S, Shepherd JD, Dehoff M, Li Y, Kuhl D, Huganir RL, Price DL, Scannevin R, Troncoso JC, Wong PC, Worley PF (2011) Arc/Arg3.1 regulates an endosomal pathway essential for activity-dependent beta-amyloid generation. Cell 147(3):615-628
132. Zhang Y, Kurup P, Xu J, Carty N, Fernandez SM, Nygaard HB, Pittenger C, Greengard P, Strittmatter SM, Nairn AC, Lombroso PJ (2010) Genetic reduction of striatal-enriched tyrosine phosphatase (STEP) reverses cognitive and cellular deficits in an Alzheimer's disease mouse model. Proc Natl Acad Sci USA 107(44):19014-19019
133. Sharma A, Hoeffer CA, Takayasu Y, Miyawaki T, McBride SM, Klann E, Zukin RS (2010) Dysregulation of mTOR signaling in fragile X syndrome. J Neurosci 30(2):694-702
134. Hou L, Klann E (2004) Activation of the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin signaling pathway is required for metabotropic glutamate receptor-dependent longterm depression. J Neurosci 24(28):6352-6361 (Pubitemid 38944226)
135. Rong R, Ahn JY, Huang H, Nagata E, Kalman D, Kapp JA, Tu J, Worley PF, Snyder SH, Ye K (2003) PI3 kinase enhancer-Homer complex couples mGluRI to PI3 kinase, preventing neuronal apoptosis. Nat Neurosci 6(11):1153-1161 (Pubitemid 37346035)
136. Giuffrida R, Musumeci S, D'Antoni S, Bonaccorso CM, Gi-uffrida-Stella AM, Oostra BA, Catania MV (2005) A reduced number of metabotropic glutamate subtype 5 receptors are associated with constitutive homer proteins in a mouse model of fragile X syndrome. J Neurosci 25(39):8908-8916 (Pubitemid 41384459)
137. Ronesi JA, Collins KA, Hays SA, Tsai NP, Guo W, Birnbaum SG, Hu JH, Worley PF, Gibson JR, Huber KM (2012) Disrupted Homer scaffolds mediate abnormal mGluR5 function in a mouse model of fragile X syndrome. Nat Neurosci 15(3):431-440, S431
138. Auerbach BD, Osterweil EK, Bear MF (2011) Mutations causing syndromic autism define an axis of synaptic pathophysiology. Nature 480(7375):63-68
139. Osterweil EK, Chuang SC, Chubykin AA, Sidorov M, Bianchi R, Wong RK, Bear MF (2013) Lovastatin corrects excess protein synthesis and prevents epileptogenesis in a mouse model of fragile X syndrome. Neuron 77(2):243-250
140. Dolan BM, Duron SG, Campbell DA, Vollrath B, Shankaranarayana Rao BS, Ko HY, Lin GG, Govindarajan A, Choi SY, Tonegawa S (2013) Rescue of fragile X syndrome phenotypes in Fmr1 KO mice by the small-molecule PAK inhibitor FRAX486. Proc Natl Acad Sci USA 110(14):5671-5676
141. Zhou X, Lin DS, Zheng F, Sutton MA, Wang H (2010) Intracellular calcium and calmodulin link brain-derived neurotrophic factor to p70S6 kinase phosphorylation and dendritic protein synthesis. J Neurosci Res 88(7):1420-1432
142. Rayasam GV, Tulasi VK, Sodhi R, Davis JA, Ray A (2009) Glycogen synthase kinase 3: more than a namesake. Br J Pharmacol 156(6):885-898
143. Markou T, Cullingford TE, Giraldo A, Weiss SC, Alsafi A, Fuller SJ, Clerk A, Sugden PH (2008) Glycogen synthase kinases 3alpha and 3beta in cardiac myocytes: regulation and consequences of their inhibition. Cell Signal 20(1):206-218 (Pubitemid 350138382)
144. Min WW, Yuskaitis CJ, Yan Q, Sikorski C, Chen S, Jope RS, Bauchwitz RP (2009) Elevated glycogen synthase kinase-3 activity in Fragile X mice: key metabolic regulator with evidence for treatment potential. Neuropharmacology 56(2):463-472
145. Yuskaitis CJ, Mines MA, King MK, Sweatt JD, Miller CA, Jope RS (2010) Lithium ameliorates altered glycogen synthase kinase-3 and behavior in a mouse model of fragile X syndrome. Biochem Pharmacol 79(4):632-646
146. Guo W, Murthy AC, Zhang L, Johnson EB, Schaller EG, Allan AM, Zhao X (2012) Inhibition of GSK3beta improves hippocampus-dependent learning and rescues neurogenesis in a mouse model of fragile X syndrome. Hum Mol Genet 21(3):681-691
147. Strumbos JG, Brown MR, Kronengold J, Polley DB, Kaczmarek LK (2010) Fragile X mental retardation protein is required for rapid experience-dependent regulation of the potassium channel Kv3.1b. J Neurosci 30(31):10263-10271
148. Gross C, Yao X, Pong DL, Jeromin A, Bassell GJ (2011) Fragile X mental retardation protein regulates protein expression and mRNA translation of the potassium channel Kv4.2. J Neurosci 31(15):5693-5698
149. Muddashetty RS, Kelic S, Gross C, Xu M, Bassell GJ (2007) Dysregulated metabotropic glutamate receptor-dependent translation of AMPA receptor and postsynaptic density-95 mRNAs at synapses in a mouse model of fragile X syndrome. J Neurosci 27(20):5338-5348 (Pubitemid 46790157)
150. Curia G, Papouin T, Seguela P, Avoli M (2009) Downregulation of tonic GABAergic inhibition in a mouse model of fragile X syndrome. Cereb Cortex 19(7):1515-1520
151. D'Hulst C, De Geest N, Reeve SP, Van Dam D, De Deyn PP, Hassan BA, Kooy RF (2006) Decreased expression of the GABAA receptor in fragile X syndrome. Brain Res 1121(1): 238-245 (Pubitemid 44708899)
152. El Idrissi A, Ding XH, Scalia J, Trenkner E, Brown WT, Dobkin C (2005) Decreased GABA(A) receptor expression in the sei-zure-prone fragile X mouse. Neurosci Lett 377(3):141-146 (Pubitemid 40332346)
153. Heulens I, D'Hulst C, Van Dam D, De Deyn PP, Kooy RF (2012) Pharmacological treatment of fragile X syndrome with GABAergic drugs in a knockout mouse model. Behav Brain Res 229(1):244-249
154. Olmos-Serrano JL, Corbin JG, Burns MP (2011) The GABA(A) receptor agonist THIP ameliorates specific behavioral deficits in the mouse model of fragile X syndrome. Dev Neurosci 33(5):395-403
155. Pacey LK, Heximer SP, Hampson DR (2009) Increased GABA(B) receptor-mediated signaling reduces the susceptibility of fragile X knockout mice to audiogenic seizures. Mol Pharmacol 76(1):18-24
156. Henderson C, Wijetunge L, Kinoshita MN, Shumway M, Hammond RS, Postma FR, Brynczka C, Rush R, Thomas A, Paylor R, Warren ST, Vanderklish PW, Kind PC, Carpenter RL, Bear MF, Healy AM (2012) Reversal of disease-related pathologies in the fragile X mouse model by selective activation of GABA(B) receptors with arbaclofen. Sci Transl Med 4(152):152ra128
157. Berry-Kravis EM, Hessl D, Rathmell B, Zarevics P, Cherubini M, Walton-Bowen K, Mu Y, Nguyen DV, Gonzalez-Heydrich J, Wang PP, Carpenter RL, Bear MF, Hagerman RJ (2012) Effects of STX209 (arbaclofen) on neurobehavioral function in children and adults with fragile X syndrome: a randomized, controlled, phase 2 trial. Sci Transl Med 4(152):152ra127
158. Schutt J, Falley K, Richter D, Kreienkamp HJ, Kindler S (2009) Fragile X mental retardation protein regulates the levels of scaffold proteins and glutamate receptors in postsynaptic densities. J Biol Chem 284(38):25479-25487
159. Krueger DD, Osterweil EK, Chen SP, Tye LD, Bear MF (2011) Cognitive dysfunction and prefrontal synaptic abnormalities in a mouse model of fragile X syndrome. Proc Natl Acad Sci USA 108(6):2587-2592
160. Erickson CA, Wink LK, Ray B, Early MC, Stiegelmeyer E, Mathieu-Frasier L, Patrick V, Lahiri DK, McDougle CJ (2013) Impact of acamprosate on behavior and brain-derived neurotrophic factor: an open-label study in youth with fragile X syndrome. Psychopharmacology 228(1):75-84
161. Utari A, Chonchaiya W, Rivera SM, Schneider A, Hagerman RJ, Faradz SM, Ethell IM, Nguyen DV (2010) Side effects of minocycline treatment in patients with fragile X syndrome and exploration of outcome measures. Am J Intellect Dev Disabil 115(5):433-443
162. Paribello C, Tao L, Folino A, Berry-Kravis E, Tranfaglia M, Ethell IM, Ethell DW (2010) Open-label add-on treatment trial of minocycline in fragile X syndrome. BMC Neurol 10:91
163. Leigh MJ, Nguyen DV, Mu Y, Winarni TI, Schneider A, Chechi T, Polussa J, Doucet P, Tassone F, Rivera SM, Hessl D, Hagerman RJ (2013) A randomized double-blind, placebo-controlled trial of minocycline in children and adolescents with fragile x syndrome. J Dev Behav Pediatr 34(3):147-155
164. Dansie LE, Phommahaxay K, Okusanya AG, Uwadia J, Huang M, Rotschafer SE, Razak KA, Ethell DW, Ethell IM (2013) Long-lasting effects of minocycline on behavior in young but not adult Fragile X mice. Neuroscience 246:186-198
165. Darnell JC, Klann E (2013) The translation of translational control by FMRP: therapeutic targets for FXS. Nat Neurosci 16(11):1530-1536
166. Dziembowska M, Pretto DI, Janusz A, Kaczmarek L, Leigh MJ, Gabriel N, Durbin-Johnson B, Hagerman RJ, Tassone F (2013) High MMP-9 activity levels in fragile X syndrome are lowered by minocycline. Am J Med Genet A 161A(8):1897-1903
167. Lohith TG, Osterweil EK, Fujita M, Jenko KJ, Bear MF, Innis RB (2013) Is metabotropic glutamate receptor 5 upregulated in prefrontal cortex in fragile X syndrome? Mol Autism 4(1):15
168. Zalfa F, Giorgi M, Primerano B, Moro A, Di Penta A, Reis S, Oostra B, Bagni C (2003) The fragile X syndrome protein FMRP associates with BC1 RNA and regulates the translation of specific mRNAs at synapses. Cell 112(3):317-327 (Pubitemid 36183653)
169. Kao DI, Aldridge GM, Weiler IJ, Greenough WT (2010) Altered mRNA transport, docking, and protein translation in neurons lacking fragile X mental retardation protein. Proc Natl Acad Sci USA 107(35):15601-15606
170. Hoeffer CA, Sanchez E, Hagerman RJ, Mu Y, Nguyen DV, Wong H, Whelan AM, Zukin RS, Klann E, Tassone F (2012) Altered mTOR signaling and enhanced CYFIP2 expression levels in subjects with fragile X syndrome. Genes Brain Behav 11(3):332-341
171. Tsai NP, Wilkerson JR, Guo W, Maksimova MA, DeMartino GN, Cowan CW, Huber KM (2012) Multiple autism-linked genes mediate synapse elimination via proteasomal degradation of a synaptic scaffold PSD-95. Cell 151(7):1581-1594
172. Sung YJ, Dolzhanskaya N, Nolin SL, Brown T, Currie JR, Denman RB (2003) The fragile X mental retardation protein FMRP binds elongation factor 1A mRNA and negatively regulates its translation in vivo. J Biol Chem 278(18):15669-15678 (Pubitemid 36799677)
173. Huang F, Chotiner JK, Steward O (2005) The mRNA for elongation factor 1alpha is localized in dendrites and translated in response to treatments that induce long-term depression. J Neurosci 25(31):7199-7209 (Pubitemid 41113936)
174. Schaeffer C, Bardoni B, Mandel JL, Ehresmann B, Ehresmann C, Moine H (2001) The fragile X mental retardation protein binds specifically to its mRNA via a purine quartet motif. EMBO J 20(17):4803-4813 (Pubitemid 32848632)
175. Miyashiro KY, Beckel-Mitchener A, Purk TP, Becker KG, Barret T, Liu L, Carbonetto S, Weiler IJ, Greenough WT, Eberwine J (2003) RNA cargoes associating with FMRP reveal deficits in cellular functioning in Fmr1 null mice. Neuron 37(3):417-431 (Pubitemid 36183364)
176. Erickson CA, Mullett JE, McDougle CJ (2009) Open-label memantine in fragile X syndrome. J Autism Dev Disord 39(12):1629-1635
177. Brager DH, Akhavan AR, Johnston D (2012) Impaired dendritic expression and plasticity of h-channels in the fmr1(-/y) mouse model of fragile X syndrome. Cell Rep 1(3):225-233
178. Menon L, Mader SA, Mihailescu MR (2008) Fragile X mental retardation protein interactions with the microtubule associated protein 1B RNA. RNA 14(8):1644-1655
179. Chen YL, Shen CK (2013) Modulation of mGluR-dependent MAP1B translation and AMPA receptor endocytosis by microRNA miR-146a-5p. J Neurosci 33(21):9013-9020
180. Zhang Y, Venkitaramani DV, Gladding CM, Zhang Y, Kurup P, Molnar E, Collingridge GL, Lombroso PJ (2008) The tyrosine phosphatase STEP mediates AMPA receptor endocytosis after metabotropic glutamate receptor stimulation. J Neurosci 28(42):10561-10566
181. Menon L, Mihailescu MR (2007) Interactions of the G quartet forming semaphorin 3F RNA with the RGG box domain of the fragile X protein family. Nucleic Acids Res 35(16):5379-5392 (Pubitemid 47423912)