New perspectives on the biology of fragile X syndrome

Current Opinion in Genetics and Development

Volumn 22, Issue 3, 2012, Pages 256-263

  Wang, Tao ^a,b   Bray, Steven M ^b   Warren, Stephen T ^b  

^a EMORY UNIVERSITY   (United States)

^b EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARGONAUTE PROTEIN; CYTOSINE; DICER; FRAGILE X MENTAL RETARDATION PROTEIN; GUANINE; MAMMALIAN TARGET OF RAPAMYCIN; METABOTROPIC RECEPTOR 1; METABOTROPIC RECEPTOR 5; MICRORNA; PHOSPHATIDYLINOSITOL 3 KINASE;

FMR1 GENE; FRAGILE X SYNDROME; GENE LOSS; GENE MUTATION; GENE SILENCING; HUMAN; MISSENSE MUTATION; NERVE CELL; NERVOUS SYSTEM DEVELOPMENT; NONHUMAN; PLURIPOTENT STEM CELL; PRESYNAPTIC NERVE; PRIORITY JOURNAL; REVIEW; RIBOSOME; SIGNAL TRANSDUCTION; STEM CELL; TRANSLATION REGULATION; TRINUCLEOTIDE REPEAT;

ALLELES; ELECTRICAL SYNAPSES; EPIGENESIS, GENETIC; FRAGILE X MENTAL RETARDATION PROTEIN; FRAGILE X SYNDROME; HUMANS; INDUCED PLURIPOTENT STEM CELLS; MAP KINASE SIGNALING SYSTEM; MUTATION, MISSENSE; NEUROGENESIS; NEURONS; PHOSPHATIDYLINOSITOL 3-KINASES; PROTEIN BIOSYNTHESIS; RECEPTORS, METABOTROPIC GLUTAMATE; RNA INTERFERENCE; TOR SERINE-THREONINE KINASES;

IPS;

EID: 84862803170     PISSN: 0959437X     EISSN: 18790380     Source Type: Journal    
DOI: 10.1016/j.gde.2012.02.002     Document Type: Review

References (51)

1. Boyle L., Kaufmann W.E. The behavioral phenotype of FMR1 mutations. Am J Med Genet C: Semin Med Genet 2010, 154C:469-476.
2. Krueger D.D., Bear M.F. Toward fulfilling the promise of molecular medicine in fragile X syndrome. Annu Rev Med 2011, 62:411-429.
3. Penagarikano O., Mulle J.G., Warren S.T. The pathophysiology of fragile X syndrome. Annu Rev Genomics Hum Genet 2007, 8:109-129.
4. Bassell G.J., Warren S.T. Fragile X syndrome: loss of local mRNA regulation alters synaptic development and function. Neuron 2008, 60:201-214.
5. Ceman S., O'Donnell W.T., Reed M., Patton S., Pohl J., Warren S.T. Phosphorylation influences the translation state of FMRP-associated polyribosomes. Hum Mol Genet 2003, 12:3295-3305.
6. Stefani G., Fraser C.E., Darnell J.C., Darnell R.B. Fragile X mental retardation protein is associated with translating polyribosomes in neuronal cells. J Neurosci 2004, 24:7272-7276.
7. Wang H., Dictenberg J.B., Ku L., Li W., Bassell G.J., Feng Y. Dynamic association of the fragile X mental retardation protein as a messenger ribonucleoprotein between microtubules and polyribosomes. Mol Biol Cell 2008, 19:105-114.
8. Darnell J.C., Van Driesche S.J., Zhang C., Hung K.Y., Mele A., Fraser C.E., Stone E.F., Chen C., Fak J.J., Chi S.W., et al. FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism. Cell 2011, 146:247-261.
9. Jin P., Zarnescu D.C., Ceman S., Nakamoto M., Mowrey J., Jongens T.A., Nelson D.L., Moses K., Warren S.T. Biochemical and genetic interaction between the fragile X mental retardation protein and the microRNA pathway. Nat Neurosci 2004, 7:113-117.
10. Li X., Jin P. Macro role(s) of microRNAs in fragile X syndrome?. Neuromol Med 2009, 11:200-207.
11. Edbauer D., Neilson J.R., Foster K.A., Wang C.F., Seeburg D.P., Batterton M.N., Tada T., Dolan B.M., Sharp P.A., Sheng M. Regulation of synaptic structure and function by FMRP-associated microRNAs miR-125b and miR-132. Neuron 2010, 65:373-384.
12. Muddashetty R.S., Nalavadi V.C., Gross C., Yao X., Xing L., Laur O., Warren S.T., Bassell G.J. Reversible inhibition of PSD-95 mRNA translation by miR-125a, FMRP phosphorylation, and mGluR signaling. Mol Cell 2011, 42:673-688.
13. Cheever A., Ceman S. Phosphorylation of FMRP inhibits association with Dicer. RNA 2009, 15:362-366.
14. De Rubeis S., Bagni C. Regulation of molecular pathways in the fragile X syndrome: insights into autism spectrum disorders. J Neurodev Disord 2011, 3:257-269.
15. Napoli I., Mercaldo V., Boyl P.P., Eleuteri B., Zalfa F., De Rubeis S., Di Marino D., Mohr E., Massimi M., Falconi M., et al. The fragile X syndrome protein represses activity-dependent translation through CYFIP1, a new 4E-BP. Cell 2008, 134:1042-1054.
16. Bechara E.G., Didiot M.C., Melko M., Davidovic L., Bensaid M., Martin P., Castets M., Pognonec P., Khandjian E.W., Moine H., et al. A novel function for fragile X mental retardation protein in translational activation. PLoS Biol 2009, 7:e16.
17. Zalfa F., Eleuteri B., Dickson K.S., Mercaldo V., De Rubeis S., di Penta A., Tabolacci E., Chiurazzi P., Neri G., Grant S.G., et al. A new function for the fragile X mental retardation protein in regulation of PSD-95 mRNA stability. Nat Neurosci 2007, 10:578-587.
18. Zhang M., Wang Q., Huang Y. Fragile X mental retardation protein FMRP and the RNA export factor NXF2 associate with and destabilize Nxf1 mRNA in neuronal cells. Proc Natl Acad Sci USA 2007, 104:10057-10062.
19. Gross C., Nakamoto M., Yao X., Chan C.B., Yim S.Y., Ye K., Warren S.T., Bassell G.J. Excess phosphoinositide 3-kinase subunit synthesis and activity as a novel therapeutic target in fragile X syndrome. J Neurosci 2010, 30:10624-10638.
20. Hoeffer C.A., Klann E. mTOR signaling: at the crossroads of plasticity, memory and disease. Trends Neurosci 2010, 33:67-75.
21. Sharma A., Hoeffer C.A., Takayasu Y., Miyawaki T., McBride S.M., Klann E., Zukin R.S. Dysregulation of mTOR signaling in fragile X syndrome. J Neurosci 2010, 30:694-702.
22. Huber K.M., Gallagher S.M., Warren S.T., Bear M.F. Altered synaptic plasticity in a mouse model of fragile X mental retardation. Proc Natl Acad Sci USA 2002, 99:7746-7750.
23. Nakamoto M., Nalavadi V., Epstein M.P., Narayanan U., Bassell G.J., Warren S.T. Fragile X mental retardation protein deficiency leads to excessive mGluR5-dependent internalization of AMPA receptors. Proc Natl Acad Sci USA 2007, 104:15537-15542.
24. Osterweil E.K., Krueger D.D., Reinhold K., Bear M.F. Hypersensitivity to mGluR5 and ERK1/2 leads to excessive protein synthesis in the hippocampus of a mouse model of fragile X syndrome. J Neurosci 2010, 30:15616-15627.
25. Olmos-Serrano J.L., Paluszkiewicz S.M., Martin B.S., Kaufmann W.E., Corbin J.G., Huntsman M.M. Defective GABAergic neurotransmission and pharmacological rescue of neuronal hyperexcitability in the amygdala in a mouse model of fragile X syndrome. J Neurosci 2010, 30:9929-9938.
26. Levenga J., de Vrij F.M., Oostra B.A., Willemsen R. Potential therapeutic interventions for fragile X syndrome. Trends Mol Med 2010, 16:516-527.
27. Deng P.Y., Sojka D., Klyachko V.A. Abnormal presynaptic short-term plasticity and information processing in a mouse model of fragile X syndrome. J Neurosci 2011, 31:10971-10982.
28. Klemmer P., Meredith R.M., Holmgren C.D., Klychnikov O.I., Stahl-Zeng J., Loos M., van der Schors R.C., Wortel J., de Wit H., Spijker S., et al. Proteomics, ultrastructure, and physiology of hippocampal synapses in a fragile X syndrome mouse model reveal presynaptic phenotype. J Biol Chem 2011, 286:25495-25504.
29. Brown M.R., Kronengold J., Gazula V.R., Chen Y., Strumbos J.G., Sigworth F.J., Navaratnam D., Kaczmarek L.K. Fragile X mental retardation protein controls gating of the sodium-activated potassium channel Slack. Nat Neurosci 2010, 13:819-821.
30. Deng W., Aimone J.B., Gage F.H. New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory?. Nat Rev Neurosci 2010, 11:339-350.
31. Ming G.L., Song H. Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron 2011, 70:687-702.
32. Guo W., Allan A.M., Zong R., Zhang L., Johnson E.B., Schaller E.G., Murthy A.C., Goggin S.L., Eisch A.J., Oostra B.A., et al. Ablation of Fmrp in adult neural stem cells disrupts hippocampus-dependent learning. Nat Med 2011, 17:559-565.
33. Luo Y., Shan G., Guo W., Smrt R.D., Johnson E.B., Li X., Pfeiffer R.L., Szulwach K.E., Duan R., Barkho B.Z., et al. Fragile X mental retardation protein regulates proliferation and differentiation of adult neural stem/progenitor cells. PLoS Genet 2010, 6:e1000898.
34. Han X.D., Powell B.R., Phalin J.L., Chehab F.F. Mosaicism for a full mutation, premutation, and deletion of the CGG repeats results in 22% FMRP and elevated FMR1 mRNA levels in a high-functioning fragile X male. Am J Med Genet A 2006, 140:1463-1471.
35. Pietrobono R., Tabolacci E., Zalfa F., Zito I., Terracciano A., Moscato U., Bagni C., Oostra B., Chiurazzi P., Neri G. Molecular dissection of the events leading to inactivation of the FMR1 gene. Hum Mol Genet 2005, 14:267-277.
36. Eiges R., Urbach A., Malcov M., Frumkin T., Schwartz T., Amit A., Yaron Y., Eden A., Yanuka O., Benvenisty N., et al. Developmental study of fragile X syndrome using human embryonic stem cells derived from preimplantation genetically diagnosed embryos. Cell Stem Cell 2007, 1:568-577.
37. Willemsen R., Bontekoe C.J., Severijnen L.A., Oostra B.A. Timing of the absence of FMR1 expression in full mutation chorionic villi. Hum Genet 2002, 110:601-605.
38. Urbach A., Bar-Nur O., Daley G.Q., Benvenisty N. Differential modeling of fragile X syndrome by human embryonic stem cells and induced pluripotent stem cells. Cell Stem Cell 2010, 6:407-411.
39. Sheridan S.D., Theriault K.M., Reis S.A., Zhou F., Madison J.M., Daheron L., Loring J.F., Haggarty S.J. Epigenetic characterization of the FMR1 gene and aberrant neurodevelopment in human induced pluripotent stem cell models of fragile X syndrome. PLoS One 2011, 6:e26203.
40. Hanna J., Cheng A.W., Saha K., Kim J., Lengner C.J., Soldner F., Cassady J.P., Muffat J., Carey B.W., Jaenisch R. Human embryonic stem cells with biological and epigenetic characteristics similar to those of mouse ESCs. Proc Natl Acad Sci USA 2010, 107:9222-9227.
41. Hanna J.H., Saha K., Jaenisch R. Pluripotency and cellular reprogramming: facts, hypotheses, unresolved issues. Cell 2010, 143:508-525.
42. He X.J., Chen T., Zhu J.K. Regulation and function of DNA methylation in plants and animals. Cell Res 2011, 21:442-465.
43. Handa V., Saha T., Usdin K. The fragile X syndrome repeats form RNA hairpins that do not activate the interferon-inducible protein kinase, PKR, but are cut by Dicer. Nucleic Acids Res 2003, 31:6243-6248.
44. Coffee B., Ikeda M., Budimirovic D.B., Hjelm L.N., Kaufmann W.E., Warren S.T. 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 2008, 146A:1358-1367.
45. 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., Oostra B.A. A deletion of 1.6kb proximal to the CGG repeat of the FMR1 gene causes the clinical phenotype of the fragile X syndrome. Hum Mol Genet 1994, 3:615-620.
46. 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., Willems P.J. A point mutation in the FMR-1 gene associated with fragile X mental retardation. Nat Genet 1993, 3:31-35.
47. Valverde R., Pozdnyakova I., Kajander T., Venkatraman J., Regan L. Fragile X mental retardation syndrome: structure of the KH1-KH2 domains of fragile X mental retardation protein. Structure 2007, 15:1090-1098.
48. Zang J.B., Nosyreva E.D., Spencer C.M., Volk L.J., Musunuru K., Zhong R., Stone E.F., Yuva-Paylor L.A., Huber K.M., Paylor R., et al. A mouse model of the human fragile X syndrome I304N mutation. PLoS Genet 2009, 5:e1000758.
49. Collins S.C., Bray S.M., Suhl J.A., Cutler D.J., Coffee B., Zwick M.E., Warren S.T. Identification of novel FMR1 variants by massively parallel sequencing in developmentally delayed males. Am J Med Genet A 2010, 152A:2512-2520.
50. Chahrour M., Zoghbi H.Y. The story of Rett syndrome: from clinic to neurobiology. Neuron 2007, 56:422-437.
51. Exome Variant Server, NHLBI Exome Sequencing Project (ESP), Seattle, WA (URL: ) (accessed October 2011). http://evs.gs.washington.edu/EVS/.