Molecular insights into mental retardation: Multiple functions for the Fragile X mental retardation protein?

Current Issues in Molecular Biology

Volumn 6, Issue 2, 2004, Pages 73-88

  Zalfa, Francesca ^a   Bagni, Claudia ^a,b  

^a UNIVERSITY OF ROME TOR VERGATA   (Italy)

^b IRCCS FONDAZIONE SANTA LUCIA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOSKELETON PROTEIN; FRAGILE X MENTAL RETARDATION PROTEIN; MESSENGER RNA; REPRESSOR PROTEIN; RIBONUCLEOPROTEIN; RNA BINDING PROTEIN;

BIOLOGICAL MODEL; CELL FUNCTION; CELL NUCLEUS; COMPLEX FORMATION; CYTOPLASM; CYTOSKELETON; DENDRITE; DISEASE ASSOCIATION; DROSOPHILA; ELECTROPHYSIOLOGY; FEMALE; FRAGILE X SYNDROME; GENE IDENTIFICATION; GENE MAPPING; GENE MUTATION; GENETIC CODE; HUMAN; INTELLECTUAL IMPAIRMENT; MALE; MENTAL DEFICIENCY; MOLECULAR BIOLOGY; MOLECULAR GENETICS; MORPHOGENESIS; NERVE CELL DIFFERENTIATION; NERVE CELL PLASTICITY; NONHUMAN; PHYSICAL DISEASE; PROTEIN DEPLETION; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; PROTEIN SYNTHESIS; REVIEW; RNA BINDING; RNA TRANSLATION; SIGNAL TRANSDUCTION; SPINE; SYMPTOMATOLOGY; SYNAPSE; TRANSLATION REGULATION; X CHROMOSOME;

ANIMALS; DROSOPHILA; FRAGILE X MENTAL RETARDATION PROTEIN; FRAGILE X SYNDROME; HUMANS; MICE; MODELS, BIOLOGICAL; NERVE TISSUE PROTEINS; NEURONS; PROTEIN STRUCTURE, TERTIARY; RNA-BINDING PROTEINS; SYNAPSES;

EID: 1942467797     PISSN: 14673037     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (150)

1. Abitbol, M., Menini, C., Delezoide, A.L., Rhyner, T., Vekemans, M., and Mallet, J. 1993. Nucleus basalis magnocellularis and hippocampus are the major sites of FMR-1 expression in the human fetal brain. Nat. Genet. 4:147-153.
2. Adinolfi, S., Bagni, C., Musco, G., Gibson, T., Mazzarella, L., and Pastore, A. 1999a. Dissecting FMR1, the protein responsible for fragile X syndrome, in its structural and functional domains. RNA 9:1248-1258.
3. Adinolfi, S., Bagni, C., Castiglione Morelli, M.A., Fraternali, F., Musco, G., and Pastore, A. 1999b. Novel RNA-binding motif: the KH module. Biopolymers 51:153-164.
4. Adinolfi, S., Ramos, A., Martin, S.R., Dal Piaz, F., Pucci, P., Bardoni, B., Madel, J.L, and Pastore, A. 2003. The N-Terminus of the Fragile X Mental Retardation Protein contains a novel domain involved in dimerization and RNA-binding. Biochemistry. 42: 10437-10444.
5. Allingham-Hawkins, D.J., Babul-Hirji, R., Chitayat, D., Holden, J.J., Yang, K.T., Lee, C., Hudson, R., Gorwill, H., Nolin, S.L., Glicksman, A., Jenkins, E.C., Brown, W.T., Howard-Peebles, P.N., Becchi, C., Cummings, E., Fallon, L., Seitz, S., Black, S.H., Vianna-Morgante, A.M., Costa, S.S., Otto, P.A., Mingroni-Netto, R.C., Murray, A., Webb, J., Vieri, F., et al. 1999. Fragile X premutation is a significant risk factor for premature ovarian failure: the International Collaborative POF in Fragile X study - preliminary data. Am. J. Med. Genet. 3:322-325.
6. Antar, L.N., and Bassell, G.J. 2003. Sunrise at the synapse: the FMRP mRNP shaping the synaptic interface. Neuron 37:555-558.
7. Ashley, C.T., Jr., Wilkinson, K.D., Reines, D., and Warren, S.T. 1993. FMR1 protein: conserved RNP family domains and selective RNA binding. Science 262:563-566.
8. Bagni, C., and Lapeyre, B. 1998. Gar1p binds to the small nucleolar RNAs snR10 and snR30 in vitro through a nontypical RNA binding element. J. Biol. Chem. 273:10868-10873.
9. Bakker, C.E., Verheij, C., Willemsen, R., Vanderhelm, R., Oerlemans, F., Vermey, M., Bygrave, A., Hoogeveen, A. T., Oostra, B.A., Reyniers, E., et al. 1994. FMR1 knockout mice: a model to study fragile X mental retardation. Cell 78:23-33.
10. Bardoni, B., Sittler, A., Shen, Y., and Mandel, J.L. 1997. Analysis of domains affecting intracellular localization of the FMRP protein. Neurobiol. Dis. 4:329-336.
11. Bardoni, B., and Mandel, J.L. 2002. Advances in understanding of fragile X pathogenesis and FMRP function, and in identification of X linked mental retardation genes. Curr. Opin. Genet. Dev. 12:284-293.
12. Bardoni, B., Castets, M., Huot, M.E., Schenck, A., Adinolfi, S., Corbin, F., Pastore, A., Khandjian, E.W., and Mandel, J.L. 2003. 82-FIP, a novel FMRP (Fragile X Mental Retardation Protein) interacting protein, shows a cell cycle-dependent intracellular localization. Hum. Mol. Genet. 12:1689-1698.
13. Baskaran, S., Datta, S., Mandal, A., Gulati, N., Totey, S., Anand, R.R., Brahmachari, V. 2002. Instability of CGG repeats in transgenic mice. Genomics. 80:151-157.
14. Bontekoe, C.J., McIlwain, K.L., Nieuwenhuizen, I.M., Yuva-Paylor, L.A., Nellis, A., Willemsen, R., Fang, Z., Kirkpatrick, L., Bakker, C.E., McAninch, R., Cheng, N.C., Merriweather, M., Hoogeveen, A, T., Nelson, D., Paylor, R., and Oostra, B.A. 2002. Knockout mouse model for Fxr2: a model for mental retardation. Hum. Mol. Genet. 11:487-498.
15. Braun, K., and Segal, M. 2000. FMRP involvement in formation of synapses among cultured hippocampal neurons. Cereb. Cortex. 10:1045-1052.
16. Brown, V., Small, K., Lakkis, L., Feng, Y., Gunter, C., Wilkinson, K.D., and Warren, S.T. 1998. Purified recombinant Fmrp exhibits selective RNA binding as an intrinsic property of the fragile X mental retardation protein. J. Biol. Chem. 273:15521-15527.
17. 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., Darnell, R.B., Warren, S.T. 2001. Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome. Cell. 107:477-487.
18. Caudy, A.A., Myers, M., Hannon, G.J., and Hammond, S.M. 2002. Fragile X-related protein and VIG associate with the RNA interference machinery. Genes. Dev. 16:2491-2496.
19. Ceman, S., Brown, V., and Warren, S.T. 1999. Isolation of an FMRP-associated messenger ribonucleoprotein particle and identification of nucleolin and the fragile X-related proteins as components of the complex. Mol. Cell. Biol. 19:7925-7932.
20. Ceman, S., Nelson, R., and Warren, S.T. 2000. Identification of mouse YB1/p50 as a component of the FMRP-associated mRNP particle. Biochem Biophys Res Commun. 279:904-908.
21. Chelly, J., and Mandel, J.L. 2001. Monogenic causes of X-linked mental retardation. Nat. Rev. Genet. 2:669-680.
22. Chiurazzi, P., Pomponi, M.G., Willemsen, R., Oostra, B.A., and Neri, G. 1998. In vitro reactivation of the FMR1 gene involved in fragile X syndrome. Hum. Mol. Genet. 7:109-113.
23. Comery, T.A., Harris, J.B., Willems, P.J., Oostra, B.A., Irwin, S.A., Weiler, I.J., and Greenough, W.T. 1997. Abnormal dendritic spines in fragile X knockout mice: maturation and pruning deficits. Proc. Natl. Acad. Sci. USA. 94:5401-5404.
24. D'Agata V, Warren ST, Zhao W, Torre ER, Alkon DL, Cavallaro S.2002. Gene expression profiles in a transgenic animal model of fragile X syndrome. Neurobiol Dis. 3:211-8.
25. Dandekar, T. 2002. RNA motifs and regulatory elements. 2nd ed. Springer.
26. Darnell, J.C., Jensen, K.B., Jin, P., Brown, V., Warren, S.T., and Darnell, R.B. 2001. Fragile X mental retardation protein targets G quartet mRNAs important for neuronal function. Cell. 107:489-499.
27. De Boulle, K., Verkerk, A.J., Reyniers, E., Vits, L., Hendrickx, J., Van Roy, B., Van den Bos, F., de Graaff, E., Oostra, B.A., and Willems, P.J. 1993. Apoint mutation in the FMR-1 gene associated with fragile X mental retardation. Nat. Genet. 3:31-35.
28. De Diego Otero, Y., Severijnen, L.A., van Cappellen, G., Schrier, M., Oostra, B., and Willemsen, R. 2002. Transport of fragile X mental retardation protein via granules in neurites of PC12 cells. Mol. Cell. Biol. 22:8332-8341.
29. Devys, D., Lutz, Y., Rouyer, N., Bellocq, J.P., and Mandel, J.L. 1993. The FMR-1 protein is cytoplasmic, most abundant in neurons and appears normal in carriers of a fragile X premutation. Nat. Genet. 4:335-340.
30. Dockendorff, T.C., Su, H.S., McBride, S.M., Yang, Z., Choi, C.H., Siwicki, K.K., Sehgal, A., and Jongens, T.A. 2002. Drosophila lacking dfmr1 activity show defects in circadian output and fail to maintain courtship interest. Neuron 34:973-984.
31. Duchaine, T.F., Hemraj, I., Furic, L., Deitinghoff, A., Kiebler, M.A., and DesGroseillers, L. 2002. Staufen2 isoforms localize to the somatodendritic domain of neurons and interact with different organelles. J. Cell. Sci. 115:3285-3295.
32. Duncan, R., Bazar, L., Michelotti, G., Tomonaga, T., Krutzsch, H., Avigan, M., and Levens, D. 1994. A sequence-specific, single-strand binding protein activates the far upstream element of c-myc and defines a new DNA-binding motif. Genes. Dev. 8:465-480.
33. Eberhart, D.E., Malter, H.E., Feng, Y., and Warren, S.T. 1996. The fragile X mental retardation protein is a ribonucleoprotein containing both nuclear localization and nuclear export signals. Hum. Mol. Genet. 5:1083-1091.
34. Eichler, E.E., Richards, S., Gibbs, R.A., and Nelson, D.L. 1993. Fine structure of the human FMR1 gene. Hum. Mol. Genet. 2:1147-1153.
35. Feng, Y., Gutekunst, C.A., Eberhart, D.E., Yi, H., Warren, S.T., and Hersch, S.M. 1997a. Fragile X mental retardation protein: nucleocytoplasmic shuttling and association with somatodendritic ribosomes. J. Neurosci. 17:1539-1547.
36. Feng, Y., Absher, D., Eberhart, D.E., Brown, V., Malter, H.E., and Warren, S.T. 1997b. FMRP associates with polyribosomes as an mRNP and the I304N mutation of severe fragile X syndrome abolishes this association. Mol. Cell 1:109-118.
37. Fouraux, M.A., Bouvet, P., Verkaart, S., van Venrooij, W.J., and Pruijn, G.J. 2002. Nucleolin associates with a subset of the human Ro ribonucleoprotein complexes. J. Mol. Biol. 320:475-488.
38. Fridell, R.A., Benson, R.E., Hua, J., Bogerd, H.P., Cullen, B.R. 1996. A nuclear role for the Fragile X mental retardation protein. EMBO J. 15:5408-5414.
39. Gedeon, A.K., Baker, E., Robinson, H., Partington, M.W., Gross, B., Manca, A., Korn, B., Poustka, A., Yu, S., Sutherland, G.R., et al. 1992. Fragile X syndrome without CCG amplification has an FMR1 deletion. Nat. Genet. 1:341-344.
40. Ghisolfi, L., Kharrat, A., Joseph, G., Amalric, F., and Erard, M. 1992. Concerted activities of the RNA recognition and the glycine-rich C-terminal domains of nucleolin are required for efficient complex formation with pre-ribosomal RNA. Eur. J. Biochem. 209:541-548.
41. Gibson, T.J., Thompson, J.D., and Heringa, J. 1993. The KH domain occurs in a diverse set of RNA-binding proteins that include the antiterminator NusA and is probably involved in binding to nucleic acid. FEBS Lett. 324:361-366.
42. Giuditta, A., Kaplan, B.B., van Minnen, J., Alvarez, J., and Koenig, E. 2002. Axonal and presynaptic protein synthesis: new insights into the biology of the neuron. Trends. Neurosci. 25:400-404.
43. Godfraind, J.M., Reyniers, E., De Boulle, K., D'Hooge, R., De Deyn, P.P., Bakker, C.E., Oostra, B.A., Kooy, R.F., and Willems, P.J. 1996. Long-term potentiation in the hippocampus of fragile X knockout mice. Am. J. Med. Genet. 64:246-251.
44. Greco, C.M., Hagerman, R.J., Tassone, F., Chudley, A.E., Del Bigio, M.R., Jacquemont, S., Leehey, M., and Hagerman, P.J. 2002. Neuronal intranuclear inclusions in a new cerebellar tremor/ataxia syndrome among fragile X carriers. Brain 125:1760-1771.
45. Greenough, W.T., Klintsova, A.Y., Irwin, S.A., Galvez, R., Bates, K.E., and Weiler, I.J. 2001. Synaptic regulation of protein synthesis and the fragile X protein. Proc. Natl. Acad. Sci. USA. 98:7101-7106.
46. Hagerman, R.J., Van Housen, K., Smith, A.C., and McGavran, L. 1984a. Consideration of connective tissue dysfunction in the fragile X syndrome. Am. J. Med. Genet. 17:111-121.
47. Hagerman, R.J., and Synhorst, D.P. 1984b. Mitral valve prolapse and aortic dilatation in the fragile X syndrome. Am. J. Med. Genet. 17:123-131.
48. Hagerman, R.J., and Cronister, A. 1996. Fragile X Syndrome Diagnosis, Treatment, and Re- search. Baltimore, MD:Johns. Hopkins. Univ. Press. 481pp.
49. Hagerman, R.J., Leehey, M., Heinrichs, W., Tassone, F., Wilson, R., Hills, J., Grigsby, J., Gage, B., and Hagerman, P.J. 2001. Intention tremor parkinsonism, and generalized brain atrophy in male carriers of fragile X. Neurol. 57:127-130.
50. Hinds, H.L., Ashley, C.T., Sutcliffe, J.S., Nelson, D.L., Warren, S.T., Housman, D.E., and Schalling, M. 1993. Tissue specific expression of FMR-1 provides evidence for a functional role in fragile X syndrome. Nat. Genet. 3:36-43.
51. Hinton, V.J., Brown, W.T., Wisniewski, K., and Rudelli, R.D. 1991. Analysis of neocortex in three males with the fragile X syndrom. Am. J. Med. Genet. 41:289-294.
52. Hirst, M., Grewal, P., Flannery, A., Slatter, R., Maher, E., Barton, D., Fryns, J.P., and Davies, K. 1995. Two new cases of FMR1 deletion associated with mental impairment. Am. J. Hum. Genet. 56:67-74.
53. Hollmann, M., and Heinemann, S. 1994. Cloned glutamate receptors. Annu. Rev. Neurosci. 17:31-108.
54. Huber, K.M., Gallagher, S.M., Warren, S.T., and Bear, M.F. 2002. Altered synaptic plasticity in a mouse model of fragile X mental retardation. Proc. Natl. Acad. Sci. USA. 99:7746-7750.
55. Hummel T, Krukkert K, Roos J, Davis G, Klambt C. 2000. Drosophila Futsch/22C10 is a MAP1B-like protein required for dendritic and axonal development. Neuron 26:357-370.
56. Inglis, F.M., Crockett, R., Korada, S., Abraham, W.C., Hollmann, M., and Kalb, R.G. 2002. The AMPA receptor subunit GluR1 regulates dendritic architecture of motor neurons. J. Neurosci. 22:8042-8051.
57. Irwin, S.A., Galvez, R., and Greenough, W.T. 2000. Dendritic spine structural anomalies in fragile-X mental retardation syndrome. Cereb. Cortex. 10:1038-1044.
58. Irwin, S.A., Patel, B., Idupulapati, M., Harris, J.B., Crisostomo, R.A., Larsen, B.P., Kooy, F., Willems, P.J., Cras, P., Kozlowski, P.B., Swain, R.A., Weiler, I.J., and Greenough, W.T. 2001. Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with fragile-X syndrome: a quantitative examination. Am. J. Med. Genet. 98:161-167.
59. Ishizuka, A., Siomi, M.C., and Siomi, H.. 2002. A Drosophila fragile X protein interacts with components of RNAi and ribosomal proteins. Genes. Dev. 16:2497-2508.
60. Khandjian, E.W., Corbin, F., Woerly, S., Rousseau, F. 1996. The fragile X mental retardation protein is associated with ribosomes. Nat Genet. 12:91-93.
61. Kaytor, M.D., and Orr, H.T. 2001. RNA targets of the fragile X protein. Cell 107:555-557.
62. Kawasaki, H., and Taira, K. 2003. Hes1 is a target of microRNA-23 during retinoic-acid-induced neuronal differentiation of NT2 cells. Nature 423:838-842.
63. Kenneson, A., Zhang, F., Hagedorn, C.H., and Warren, S.T. 2001. Reduced FMRP and increased FMR1 transcription is proportionally associated with CGG repeat number in intermediate-length and premutation carriers. Hum. Mol. Genet. 10:1449-1454.
64. Kiledjian, M., and Dreyfuss, G. 1992. Primary structure and binding activity of the hnRNP U protein: binding RNA through RGG box. EMBO J. 11:2655-2664.
65. Kobayashi, K., Kuroda, S., Fukata, M., Nakamura, T., Nagase, T., Nomura, N., Matsuura, Y., Yoshida-Kubomura, N., Iwamatsu, A., and Kaibuchi. 1998. p140Sra-1 (specifically Rac1-associated protein) is a novel specific target for Rac1 small GTPase. J. Biol. Chem. 273:291-295.
66. Kohrmann, M., Luo, M., Kaether, C., DesGroseillers, L., Dotti, C.G., and Kiebler, M.A. 1999. Microtubule-dependent recrutment of Staufen-green fluorescent protein into large RNA-containing granules and subsequent dendritic transport in living hippocampal neurons. Mol. Biol. Cell 10:2945-2953.
67. Laggerbauer, B., Ostareck, D., Keidel, E.M., Ostareck-Lederer, A., and Fischer, U. 2001. Evidence that fragile X mental retardation protein is a negative regulator of translation. Hum. Mol. Genet. 10:329-338.
68. Lapeyre, B., Mariottini, P., Mathieu, C., Ferrer, P., Amaldi, F., Amalric, F., and Caizergues-Ferrer, M. 1990. Molecular cloning of Xenopus brillarin, a conserved U3 small nuclear ribonucleoprotein recognized by antisera from humans with autoimmune disease. Mol. Cell. Biol. 10:430-434.
69. Lee, W. C., Xue, Z., and Mélèse, T. 1991. The NSR1 gene encodes a protein that speci cally binds nuclear localization sequences and has two RNA recognition motifs. J. Cell Biol. 113:1-12.
70. Lengyel, J., Guy, C., Leong, V., Borge, S., and Rice, S.A. 2002. Mapping of functional regions in the amino-terminal portion of the herpes simplex virus ICP27 regulatory protein: importance of the leucine-rich nuclear export signal and RGG Box RNA-binding domain. J. Virol. 76:11866-11879.
71. Lewis, H.A., Musunuru, K., Jensen, K.B., Edo, C., Chen, H., Darnell, R.B., and Burley, S.K. 2000. Sequence-specific RNA binding by a Nova KH domain: implications for paraneoplastic disease and the fragile X syndrome. Cell 100:323-332.
72. Li, Z., Zhang, Y., Ku, L., Wilkinson, K.D., Warren, S.T., and Feng, Y. 2001. The fragile X mental retardation protein inhibits translation via interacting with mRNA. Nucleic. Acids. Res. 29:2276-2283.
73. Li, J., Pelletier, M.R., Perez Velazquez, J.L., and Carlen, P.L. 2002. Reduced cortical synaptic plasticity and GluR1 expression associated with fragile X mental retardation protein deficiency. Mol. Cell. Neurosci. 19:138-151.
74. Loehr, J.P., Synhorst, D.P., Wolfe, R.R., and Hagerman, R.J. 1986. Aortic root dilatation and mitral valve prolapse in the fragile X syndrome. Am. J. Med. Genet. 23:189-194.
75. Lubs, H.A. 1969. A marker X chromosome. Am. J. Hum. Genet. 21:231-44.
76. Mallardo M, Deitinghoff A, Muller J, Goetze B, Macchi P, Peters C, Kiebler MA. 2003. Isolation and characterization of Staufen-containing ribonucleoprotein particles from rat brain. Proc Natl Acad Sci U S A. 100:2100-2105.
77. Malter, H.E., Iber, J.C., Willemsen, R., de Graaff, E., Tarleton, J.C., Leisti, J., Warren, S.T., and Oostra, B.A. 1997. Characterization of the full fragile X syndrome mutation in fetal gametes. Nat. Genet. 15:165-169.
78. Martin, J., and Bell, J. 1943. A pedigree of mental defect showing sex-linkage. Arch. Neurol. Psychiat. 6:154-157.
79. Maurer-Stroh, S., Dickens, N.J., Hughes-Davies, L., Kouzarides, T., Eisenhaber, F., and Ponting, C.P. 2003. The Tudor domain 'Royal Family': Tudor, plant Agenet, Chromo, PWWP and MBT domains. Trends Biochem. Sci. 28:69-74.
80. Mazroui, R., Huot, M.E., Tremblay, S., Filion, C., Labelle, Y., and Khandjian, E.W. 2002. Trapping of messenger RNA by Fragile X Mental Retardation protein into cytoplasmic granules induces translation repression. Hum. Mol. Genet. 11:3007-3017.
81. Meijer, H., de Graaff, E., Merckx, D.M., Jongbloed, R.J., de Die-Smulders, C.E., Engelen, J.J., Fryns, J.P., Curfs, P.M., and Oostra, B.A. 1994. A deletion of 1.6 kb proximal to the CGG repeat of the FMR1 gene causes the clinical phenotype of the fragile X syndrome. Hum. Mol. Genet. 3:615-620.
82. Merenstein, S.A., Sobesky, W.E., Taylor, A.K., Riddle, J,E., Tran, H.X., and Hagerman, R.J. 1996. Molecular-clinical correlations in males with an expanded FMR1 mutation. Am. J. Med. Genet. 1996 64:388-394.
83. Michelotti, E.F., Michelotti, G.A., Aronsohn, A.I., and Levens, D. 1996. Heterogeneous nuclear ribonucleoprotein K is a transcription factor. Mol. Cell. Biol. 16:2350-2360.
84. Mila', M., Castellvi-Bel, S., Sanchez, A., Barcelo, A., Badenas, C., Mallolas, J., and Estivill, X. 2000. Rare variants in the promoter of the fragile X syndrome gene (FMR1). Mol. Cell. Probes. 14: 115-119.
85. Miyashiro, K.Y., Beckel-Mitchener, A., Purk, T.P., Becker, K.G., Barret, T., Liu, L., Carbonetto, S., Weiler, I.J., Greenough, W.T., and Eberwine, J. 2003. RNA cargoes associating with FMRP reveal deficits in cellular functioning in Fmr1 null mice. Neuron 37:417-431.
86. Morales, J., Hiesinger, P.R., Schroeder, A.J., Kume, K., Verstreken, P., Jackson, F.R., Nelson, D.L., and Hassan, B.A. 2002. Drosophila fragile X protein, DFXR, regulates neuronal morphology and function in the brain. Neuron 34:961-972.
87. Muddashetty, R., Khanam, T., Kondrashov, A., Bundman, M., Iacoangeli, A., Kremerskothen, J., Duning, K., Barnekow, A., Huttenhofer, A., Tiedge, H., and Brosius, J. 2002. Poly(A)-binding protein is associated with neuronal BC1 and BC200 ribonucleoprotein particles. J. Mol. Biol. 321:433-445.
88. Musco, G., Stier, G., Joseph, C., Castiglione Morelli, M.A., Nilges, M., Gibson, T.J., and Pastore, A. 1996. Three dimensional structure and stability of the KH domain: molecular insights into the fragile X syndrome. Cell 85:237-245.
89. Musumeci, S.A., Hagerman, R.J., Ferri, R., Bosco, P., Dalla Bernardina, B., Tassinari, C.A., De Sarro, G.B., and Elia, M. 1999. Epilepsy and EEG findings in males with fragile X syndrome. Epilepsia 40:1092-1099.
90. Nakayama, A.Y., and Luo, L. 2000. Intracellular signaling pathways that regulate dendritic spine morphogenesis. Hippocampus 10:582-586.
91. Nichols, R.C., Wang, X.W., Tang, J., Hamilton, B.J., High, F.A., Herschman, H.R., and Rigby, W.F. 2000. The RGG domain in hnRNP A2 affects subcellular localization. Exp. Cell. Res. 256:522-532.
92. Nimchinsky, E.A., Oberlander, A.M., and Svoboda, K. 2001 Abnormal development of dendritic spines in FMR1 knock-out mice. J. Neurosci. 21:5139-5146.
93. Nolin, S.L., Brown, W.T., Glicksman, A., Houck, G.E., Gargano, A.D., Sullivan, A., Biancalana, V., Brondum-Nielsen K., Hjalgrim, H., Holinski-Feder, E., Kooy, F., Longshore, J., Macpherson, J., Mandel, J., Matthijs, G., Rousseau, F., Steinbach, P., Vaisanen, M., von Koskull, H., and Sherman, S.L. 2003. Expansion of the FragileX CGG repeat in females with premutation or intermediate alleles. Am. J. Hum. Genet. 72:454-464.
94. Oberle', I., Rousseau, F., Heitz, D., Krez, C., Devys, D., Hanauer, A., Boue, J., Bertheas, M.F., and Mandel, J.L. 1991. Instability of a 550-base pair DNA segment and abnormal methylation in fragile X sindrome. Science 252:1097-1102.
95. O'Donnell, W.T., and Warren, S.T. 2002. A decade of molecular studies of fragile x syndrome. Annu. Rev. Neurosci. 25:315-338.
96. Ohashi S, Kobayashi S, Omori A, Ohara S, Omae A, Muramatsu T, Li Y, Anzai K. 2000. The single-stranded DNA- and RNA-binding proteins pur alpha and pur beta link BC1 RNA to microtubules through binding to the dendrite-targeting RNA motifs. J. Neurochem. 75:1781-1790.
97. Ohashi, S., Koike, K., Omori, A., Ichinose, S., Ohara, S., Kobayashi, S., Sato, T.A., and Anzai, K. 2002. Identification of mRNA/protein (mRNP) complexes containing Puralpha, mStaufen, fragile X protein, and myosin Va and their association with rough endoplasmic reticulum equipped with a kinesin motor. J. Biol. Chem. 277:37804-37810.
98. Oostra, B.A. 2002. Functions of the fragile X protein. Trends. Mol. Med. 8:102-103.
99. Opitz, J.M., Westphal, J.M., and Daniel, A. 1984. Discovery of a connective tissue dysplasia in the Martin-Bell syndrome. Am. J. Med. Genet. 17:101-109.
100. Ostroff, L.E., Fiala, J.C., Allwardt, B., and Harris, K.M. 2002. Polyribosomes redistribute from dendritic shafts into spines with enlarged synapses during LTP in developing rat hippocampal slices. Neuron 35:535-545.
101. Poncer, J.C., Esteban, J.A., and Malinow, R. 2002. Multiple mechanisms for the potentiation of AMPA receptor-mediated transmission by alpha-Ca2+/calmodulin-dependent protein kinase II. J. Neurosci. 22:4406-4411.
102. Price, D.K., Zhang, F., Ashley, C.T. Jr., and Warren, S.T. 1996. The chicken FMR1 gene is highly conserved with a CCT 5′-untranslated repeat and encodes an RNA-binding protein. Genomics 31:3-12.
103. Primerano, B., Tassone, F., Hagerman, R.J., Hagerman, P., Amaldi, F., and Bagni, C. 2002. Reduced FMR1 mRNA translation efficiency in Fragile X patients with premutations. RNA 8:1482-1488.
104. Purpura, D.P. 1974. Dendritic spine "dysgenesis" and mental retardation. Science186:1126-1128.
105. Roche, K.W., O'Brien, R.J., Mammen, A.L., Bernhardt, J., and Huganir, R.L. 1996. Characterization of multiple phosphorylation sites on the AMPA receptor GluR1 subunit. Neuron 16:1179-1188.
106. Roos, J., Hummel, T., Ng, N., Klambt, C., and Davis, G.W. 2000. Drosophila Futsch regulates synaptic microtubule organization and is necessary for synaptic growth. Neuron 26:371-382.
107. Rousseau, F., Rouillard, P., Morel, M.L., Khandjian, E.W., and Morgan, K. 1995. Prevalence of carriers of premutation-size alleles of the FMRI gene and implications for the population genetics of the fragile X syndrome. Am. J. Hum. Genet. 57:1006-1018.
108. Rozhdestvensky, T.S., Kopylov, A.M., Brosius, J., and Huttenhofer, A. 2001. Neuronal BC1 RNA structure: evolutionary conversion of a tRNA(Ala) domain into an extended stem-loop structure. RNA 7:722-730.
109. Rudelli, R.D., Brown, W.T., Wisniewski, K., Jenkins, E.C., Laure-Kamionowska, M., Connell, F., and Wisniewski, H.M. 1985. Adult fragile X syndrome. Clinico-neuropathologic findings. Acta. Neuropathol. Berl. 67:289-295.
110. Sabaratnam, M., Vroegop, P.G., and Gangadharan, S.K. 2001. Epilepsy and EEG findings in 18 males with fragile X syndrome. Seizure 10:60-63.
111. Sala C, Futai K, Yamamoto K, Worley PF, Hayashi Y, Sheng M. 2003. Inhibition of dendritic spine morphogenesis and synaptic transmission by activity-inducible protein Homer1a. J Neurosci. 23:6327-37.
112. Sandri-Goldin, R.M. 1998. ICP27 mediates HSV RNA export by shuttling through a leucine-rich nuclear export signal and binding viral intronless RNAs through an RGG motif. Genes. Dev. 12:868-879.
113. Schaeffer, C., Bardoni, B., Mandel, J.L., Ehresmann, B., Ehresmann, C., and Moine, H. 2001. The fragile X mental retardation protein binds specifically to its mRNA via a purine quartet motif. EMBO J. 20:4803-4813.
114. Schenck, A., Bardoni, B., Moro, A., Bagni, C., and Mandel, J.L. 2001. A highly conserved protein family interacting with the fragile X mental retardation protein (FMRP) and displaying selective interactions with FMRP-related proteins FXR1P and FXR2P. Proc. Natl. Acad. Sci. USA. 98:8844-8849.
115. Schenck, A., Van de Bor, V., Bardoni, B., and Giangrande, A. 2002. Novel features of dFMR1, the Drosophila orthologue of the fragile X mental retardation protein. Neurobiol. Dis. 11:53-63.
116. Schenck, A., Bardoni, B., Langmann, C., Harden, N., Mandel, J.L., and Giangrande, A. 2003. CYFIP/Sra-1 Controls Neuronal Connectivity in Drosophila and Links the Rac1 GTPase Pathway to the Fragile X Protein. Neuron 38:887-898.
117. Shtang, S., Perry, M.D., Percy, M.E. 1999. Search for a Caenorhabditis elegans FMR1 homologue: identification of a new putative RNA-binding protein (PRP-1) that hybridizes to the mouse FMR1 double K homology domain. Am. J. Med. Genet. 84:283-5.
118. Siomi, H., Matunis, M.J., Michael, W.M., and Dreyfuss, G. 1993. The pre-mRNA binding K protein contains a novel evolutionarily conserved motif. Nucleic. Acids. Res. 21:1193-1198.
119. Siomi, H., Choi, M., Siomi, M.C., Nussbaum, R.L., and 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 77:33-39.
120. Siomi, M., Siomi, H., Sauer, W.H., Srinivasan, S., Nussbaum, R.L., and Dreyfuss, G. 1995. FXR1, an autosomal homolog of the fragile X mental retardation gene. EMBO J. 14:2401-2408.
121. Siomi, M.C., Zhang, Y., Siomi, H., and Dreyfuss, G. 1996. Specific sequences in the fragile X syndrome protein FMR1 and the FXR proteins mediate their binding to 60S ribosomal subunits and the interactions among them. Mol. Cell. Biol. 16:3825-3832.
122. Sittler A, Devys D, Weber C, Mandel JL. 1996. Alternative splicing of exon 14 determines nuclear or cytoplasmic localisation of fmr1 protein isoforms. Hum. Mol. Genet. 5:95-102.
123. Snyder EM, Philpot BD, Huber KM, Dong X, Fallon JR, Bear MF. 2001. Internalization of ionotropic glutamate receptors in response to mGluR activation. Nat. Neurosci. 4:1079-1085.
124. Song I, Huganir RL. 2002. Regulation of AMPA receptors during synaptic plasticity. Trends Neurosci. 11:578-88.
125. Stevenson, R.E., Schwartz, C.E., and Schroer, R.J. 2000. X-Linked Mental Retardation. Oxford Univ. Press.
126. Steward, O., Bakker, C.E., Willems, P.J., and Oostra, B.A. 1998. No evidence for disruption of normal patterns of mRNA localization in dendrites or dendritic transport of recently synthesized mRNA in FMR1 knockout mice, a model for human fragile-X mental retardation syndrome. Neuroreport 9:477-481.
127. Steward, O., and Schuman, E.M. 2001. Protein synthesis at synaptic sites on dendrites. Annu. Rev. Neurosci. 24:299-325.
128. Sung, Y.J., Conti, J., Currie, J.R., Brown, W.T., and Denman, R.B. 2000. RNAs that interact with the fragile X syndrome RNA binding protein FMRP. Biochem. Biophys. Res. Commun. 275:973-980.
129. Sutcliffe, J.S., Nelson, D.L., Zhang, F., Pieretti, M., Caskey, C.T., Saxe, D., and Warren, S.T. 1992. DNA methylation represses FMR-1 transcription in fragile X syndrome. Hum. Mol. Genet. 1:397-400.
130. Sutherland, G.R. 1977. Fragile sites on human chromosomes: demonstration of their dependence on the type of tissue culture medium. Science 197:265-266.
131. Tamanini, F., Van Unen, L., Bakker, C., Sacchi, N., Galjaard, H., Oostra, B.A., and Hoogeveen, A.T. 1999. Oligomerization properties of fragile-X mental-retardation protein (FMRP) and the fragile-X-related proteins FXR1P and FXR2P. Biochem. J. 343:517-523.
132. Tan, S.E., Wenthold, R.J., and Soderling, T.R. 1994. Phosphorylation of AMPA-type glutamate receptors by calcium/calmodulin-dependent protein kinase II and protein kinase C incultured hippocampal neurons. J. Neurosci. 14:1123-1129.
133. Tassone, F., Hagerman, R.J., Taylor, A.K., Gane, L.W., Godfrey, T.E., and Hagerman, P.J. 2000a. Elevated levels of FMR1 mRNA in carrier males: a new mechanism of involvement in the fragile-X syndrome. Am. J. Hum. Genet. 66:6-15.
134. Tassone, F., Hagerman, R.J., Loesch, D.Z., Lachiewicz, A., Taylor, A.K., and Hagerman, P.J. 2000b. Fragile X males with unmethylated, full mutation trinucleotide repeat expansions have elevated levels of FMR1 messenger RNA. Am. J. Med. Genet. 94:232-236.
135. Turner, G., Daniel, A., and Frost, M. 1980. X-linked mental retardation, macro-orchidism, and the Xq27 fragile site. J. Pediatr. 96:837-841.
136. Uzielli, M.L., Guarducci, S., Lapi, E., Cecconi, A., Ricci, U., Ricotti, G., Biondi, C., Scarselli, B., Vieri, F., Scarnato, P., Gori, F, and Sereni A. 1999. Premature ovarian failure (POF) and fragile X premutation females: from POF to to fragile X carrier identification, from fragile X carrier diagnosis to POF association data. Am. J. Med. Genet. 84:300-303.
137. Vanderklish, P.W., and Edelman, G.M. 2002. Dendritic spines elongate after stimulation of group 1 metabotropic glutamate receptors in cultured hippocampal neurons. Proc Natl Acad Sci U S A. 99:1639-44.
138. Verheij, C., Bakker, C.E., de Graaff, E., Keulemans, J., Willemsen, R., Verkerk, A.J., Galjaard, H., Reuser, A.J., Hoogeveen, A.T., and Oostra, B.A. 1993. Characterization and localization of the FMR-1 gene product associated with fragile X syndrome. Nature 363:722-724.
139. Verkerk, A.J., Pieretti, M., Sutcliffe, J.S., Fu, Y.H., Kuhl, D.P., Pizzuti, A., Reiner, O., Richards, S., Victoria, M.F., Zhang, F.P., 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 65:905-914.
140. Verkerk, A.J., de Graaff, E., De Boulle, K., Eichler, E.E., Konecki, D.S., Reyniers, E., Manca, A., Poustka, A., Willems, P.J., Nelson, D.L., et al. 1993. Alternative splicing in the fragile X gene FMR1. Hum. Mol. Genet. 2:1348.
141. Yu, S., Pritchard, M., Kremer, E., Lynch, M., Nancarrow, J., Baker, E., Holman, K., Mulley, J.C., Warren, S.T., Schlessinger, D., et al. 1991. Fragile X genotype characterized by an unstable region of DNA. Science 252:1179-1181.
142. Wan, L., Dockendorff, T.C., Jongens, T.A., and Dreyfuss, G. 2000. Characterization of dFMR1, a Drosophila melanogaster Homolog of the Fragile X Mental Retardation Protein. Mol. Cell. Biol. 20:8536-8547.
143. Wang, H., Iacoangeli, A., Popp, S., Muslimov, I.A., Imataka, H., Sonenberg, N., Lomakin, I.B., and Tiedge, H. 2002. Dendritic BC1 RNA: functional role in regulation of translation initiation. J. Neurosci. 22:10232-10241.
144. Weiler, I.J., Irwin, S.A., Klintsova, A.Y., Spencer, C.M., Brazelton, A.D., Miyashiro, K., Comery, T.A., Patel, B., Eberwine, J., and Greenough, W.T. 1997. Fragile X mental retardation protein is translated near synapses in response to neurotransmitter activation. Proc. Natl. Acad. Sci. USA. 94:5395-5400.
145. Willemsen, R., Hoogeveen-Westerveld, M., Reis, S., Holstege, J., Severijnen, L.A., Nieuwenhuizen, I.M., Schrier, M., Van Unen, L., Tassone, F., Hoogeveen, A.T., Hagerman, P.J., Mientjes, E.J., and Oostra, B.A. 2003. The FMR1 CGG repeat mouse displays ubiquitin-positive intranuclear neuronal inclusions; implications for the cerebellar tremor/ataxia syndrome. Hum. Mol. Genet. 12:949-959.
146. Wohrle, D., Kotzot, D., Hirst, M.C., Manca, A., Korn, B., Schmidt, A., Barbi, G., Rott, H.D., Poustka, A., Davies, K.E., et al. 1992. A microdeletion of less than 250 kb, including the proximal part of the FMR-I gene and the fragile-X site, in a male with the clinical phenotype of fragile-X syndrome. Am. J. Hum. Genet. 51:299-306.
147. Zalfa, F., Giorgi, M., Primerano, B., Moro, A., Di Penta, A., Reis, S., Oostra, B.A., and Bagni, C. 2003. The Fragile X Syndrome Protein FMRP Associates with BC1 RNA and Regulates the Translation of Specific mRNAs at Synapses. Cell 112:317-327.
148. Zhang, Y., O'Connor, J.P., Siomi, M.C., Srinivasan, S., Dutra, A., Nussbaum, R.L., and Dreyfuss, G. 1995. The Fragile X Mental Retardation Syndrome protein interacts with novel homologs FXR1 and FXR2. EMBO J. 14:5358-5366.
149. Zhang, S., and Grosse, F. 1997. Domain structure of human nuclear DNA helicase II (RNA helicase A). J. Biol. Chem. 272:11487-11494.
150. Zhang, Y.Q., Bailey, A.M., Matthies, H.J., Renden, R.B., Smith, M.A., Speese, S.D., Rubin, G.M., and Broadie, K. 2001. Drosophila fragile X-related gene regulates the MAP1B homolog Futsch to control synaptic structure and function. Cell 107:591-603.