CYFIP family proteins between autism and intellectual disability: Links with fragile X syndrome

Frontiers in Cellular Neuroscience

Volumn 8, Issue MAR, 2014, Pages

  Abekhoukh, Sabiha ^a,b,c   Bardoni, Barbara ^a,b,c  

^a INSTITUT DE PHARMACOLOGIE MOLÉCULAIRE ET CELLULAIRE   (France)

^b UNIVERSITÉ CÔTE D'AZUR   (France)

^c CNRS   (France)

Author keywords

Autism; CYFIP family proteins; Dendritic spines; F actin; Fragile X; Intellectual disability; Wave complex

Indexed keywords

CYTOPLASMIC FMR1 INTERACTING PROTEIN 1; FRAGILE X MENTAL RETARDATION PROTEIN; INITIATION FACTOR 4E BINDING PROTEIN 1; MESSENGER RNA; METABOTROPIC RECEPTOR; N METHYL DEXTRO ASPARTIC ACID; NUCLEIC ACID BINDING PROTEIN; PROTEIN P53; RAC1 PROTEIN; RNA BINDING PROTEIN; UNCLASSIFIED DRUG; WAVE PROTEIN;

ACTIN POLYMERIZATION; AUTISM; CELL FUNCTION; DENDRITIC SPINE; ELECTROPHYSIOLOGY; FRAGILE X SYNDROME; GENE INTERACTION; GENETIC PARAMETERS; HUMAN; HUMAN CELL; INTELLECTUAL IMPAIRMENT; LONG TERM POTENTIATION; NERVE CELL; NERVE POTENTIAL; NERVOUS SYSTEM PARAMETERS; NEUROTRANSMISSION; NONHUMAN; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; SYNAPTIC TRANSMISSION; TRANSLATION REGULATION;

EID: 84897088758     PISSN: 16625102     EISSN: None     Source Type: Journal    
DOI: 10.3389/fncel.2014.00081     Document Type: Review

References (87)

1. Anitei, M., Stange, C., Parshina, I., Baust, T., Schenck, A., Raposo, G., et al. (2010). Protein complexes containing CYFIP/Sra/PIR121 coordinateArf1 and Rac1 signalling during clathrin-AP-1-coated carrier biogenesis at the TGN. Nat. Cell Bio. 12, 330-340. doi: 10.1038/ncb2034.
2. Aschrafi, A., Cunningham, B. A., Edelman, G. M., and Vanderklish, P. W. (2005). The fragile X mental retardation protein and group I metabotropic glutamate receptors regulate levels of mRNA granules in brain. Proc. Natl. Acad. Sci. U.S.A. 102, 2180-2185. doi: 10.1073/pnas.0409803102.
3. Auerbach, B. D., Osterweil, E. K., and Bear, M. F. (2011). Mutations causing syndromic autism define an axis of synaptic pathophysiology. Nature 480, 63-68. doi: 10.1038/nature10658.
4. Bardoni, B., Abekhoukh, S., Zongaro, S., and Melko, M. (2012). Intellectual disabilities, neuronal posttranscriptional RNA metabolism, and RNA-binding proteins: three actors for a complex scenario. Prog. Brain Res. 197, 29-51. doi: 10.1016/B978-0-444-54299-1.00003-0.
5. Bardoni, B., Mandel, J.L., andFisch, G.S. (2000). Fmr1 gene andfragileXsyndrome. Am. J. Med. Genet. 97, 153-163. doi: 10.1002/1096-8628(200022)97:2<153::AID-AJMG7>3.0.C0;2-M
6. Bittel, D. C., Kibiryeva, N., and Butler, M. G. (2006). Expression of 4 genes between chromosome 15 breakpoints 1 and 2 and behavioral outcomes in Prader-Willi syndrome. Pediatrics 118, e1276-e1283. doi: 10.1542/peds.2006-0424.
7. Bogdan, S., Grewe, O., Strunk, M., Mertens, A., and Klambt, C. (2004). Sra-1 interacts with Kette and Wasp and is required for neuronal and bristle development in Drosophila. Development 131, 3981-3989. doi: 10.1242/dev.01274.
8. Bozdagi, O., Sakurai, T., Dorr, N., Pilorge, M., Takahashi, N., and Buxbaum, J. D. (2012). Haploinsufficiencyof Cyfip1 produces fragile X-like phenotypes in mice. PLoS ONE 7:e42422. doi: 10.1371/journal.pone.0042422
9. Brentani, H., De Paula, C. S., Bordini, D., Rolim, D., Sato, F., Portolese, J., et al. (2013). Autism spectrum disorders: an overview on diagnosis and treatment. Rev. Bras. Psiquiatr. 35(Suppl. 1), S62-S72. doi: 10.1590/1516-4446-2013-S104
10. Brown, V., Jin, P., Ceman, S., Darnell, J. C., O'Donnell, W. T., Tenenbaum, S. A., et al. (2001). Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome. Cell 107, 477-487. doi: 10.1016/S0092-8674(01)00568-2.
11. Browne, C. E., Dennis, N. R., Maher, E., Long, F. L., Nicholson, J. C., Sillibourne, J., et al. (1997). Inherited interstitial duplications of proximal 15q: genotype-phenotype correlations. Am. J. Hum. Genet. 61, 1342-1352. doi: 10.1086/301624
12. Buiting, K. (2010). Prader-Willi syndrome and Angelman syndrome. Am. J. Med. Genet. CSemin. Med. Genet. 154C, 365-376. doi: 10.1002/ajmg.c.30273.
13. Bureau, I., Shepherd, G. M., and Svoboda, K. (2008). Circuit and plasticity defects in the developing somatosensory cortex of FMR1 knock-out mice. J. Neurosci. 28, 5178-5188. doi: 10.1523/JNEUR0SCI.1076-08.2008.
14. Cassidy, S. B., Dykens, E., and Williams, C. A. (2000). Prader-Willi and Angelman syndromes: sister imprinted disorders. Am. J. Med. Genet. 97, 136-146. doi: 10.1002/1096-8628(200022)97:2<136::AID-AJMG5>3.0.C0;2-V
15. Castets, M., Schaeffer, C., Bechara, E., Schenck, A., Khandjian, E. W., Luche, S., et al. (2005). FMRP interferes with the Rac1 pathway and controls actin cytoskeleton dynamics in murine fibroblasts. Hum. Mol. Genet. 14, 835-844. doi: 10.1093/hmg/ddi077.
16. Chen, B., Brinkmann, K., Chen, Z., Pak, C. W., Liao, Y., Shi, S., et al. (2014). The WAVE regulatory complex links diverse receptors to the actin cytoskeleton. Cell 156, 195-207. doi: 10.1016/j.cell.2013.11.048.
17. Chen, Z., Borek, D., Padrick, S. B., Gomez, T. S., Metlagel, Z., Ismail, A. M., et al. (2010). Structure andcontrol of the actin regulatoryWAVEcomplex. Nature 468, 533-538. doi: 10.1038/nature09623.
18. Chuang, S. C., Zhao, W., Bauchwitz, R., Yan, Q., Bianchi, R., and Wong, R. K. (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, 8048-8055. doi: 10.1523/JNEUR0SCI.1777-05.2005.
19. Comery, T. A., Harris, J. B., Willems, P. J., Oostra, B. A., Irwin, S. A., Weiler, I. J., et al. (1997). Abnormal dendritic spines in fragile X knockout mice: maturation and pruning deficits. Proc. Natl. Acad. Sci. U.S.A. 94, 5401-5404. doi: 10.1073/pnas.94.10.5401.
20. Conrad, B., andAntonarakis, S. E. (2007). Gene duplication: a drive for phenotypic diversityandcauseofhumandisease. Annu. Rev. GenomicsHum. Genet. 8, 17-35. doi: 10.1146/annurev.genom.8.021307.110233.
21. Corbin, F., Bouillon, M., Fortin, A., Morin, S., Rousseau, F., and Khandjian, E. W. (1997). The fragile X mental retardation protein is associated with poly(A)+ mRNA in actively translating polyribosomes. Hum. Mol. Genet. 6, 1465-1472. doi: 10.1093/hmg/6.9.1465.
22. Cory, G. O., and Ridley, A. J. (2002). Cell motility: braking WAVEs. Nature 418, 732-733. doi: 10.1038/418732a
23. Dang, I., Gorelik, R., Sousa-Blin, C., Derivery, E., Guerin, C., Linkner, J., et al. (2013). Inhibitorysignalling to the Arp2/3 complex steers cell migration. Nature 503, 281-284. doi:10.1038/nature12611.
24. Darnell, J. C., Van Driesche, S. J., Zhang, C., Hung, K. Y., Mele, A., Fraser, C. E., et al. (2011). FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism. Cell 146, 247-261. doi: 10.1016/j.cell.2011. 06.013
25. Davidovic, L., Navratil, V., Bonaccorso, C. M., Catania, M. V., Bardoni, B., and Dumas, M. E. (2011). A metabolomic and systems biology perspective on the brain of the fragile X syndrome mouse model. Genome Res. 21, 2190-2202. doi: 10.1101/gr.116764.110.
26. De Kovel, C. G., Trucks, H., Helbig, I., Mefford, H. C., Baker, C., Leu, C., et al. (2010). Recurrent microdeletions at 15q11.2 and 16p13.11 predispose to idiopathic generalized epilepsies. Brain 133, 23-32. doi: 10.1093/brain/awp262.
27. De Rubeis, S., Pasciuto, E., Li, K. W., Fernandez, E., Di Marino, D., Buzzi, A., et al. (2013). CYFIP1 coordinates mRNA translation and cytoskeleton remodeling to ensure proper dendritic spine formation. Neuron 79, 1169-1182. doi: 10.1016/j.neuron.2013.06.039.
28. Derivery, E., Lombard, B., Loew, D., and Gautreau, A. (2009). The Wave complex is intrinsicallyinactive. CellMotil. Cytoskeleton 66, 777-790. doi: 10.1002/cm.20342.
29. Dolen, G., Carpenter, R. L., Ocain, T. D., and Bear, M. F. (2010). Mechanism-based approaches to treating fragile X. Pharmacol. Ther. 127, 78-93. doi: 10.1016/j.pharmthera.2010.02.008.
30. Doornbos, M., Sikkema-Raddatz, B., Ruijvenkamp, C. A., Dijkhuizen, T., Bijlsma, E. K., Gijsbers, A. C., et al. (2009). Nine patients with a microdeletion 15q11.2 between breakpoints 1 and 2 of the Prader-Willi critical region, possibly associated with behavioural disturbances. Eur. J. Hum. Genet. 52, 108-115. doi: 10.1016/j.ejmg.2009.03.010.
31. Dubielecka, P. M., Ladwein, K. I., Xiong, X., Migeotte, I., Chorzalska, A., Anderson, K. V., et al. (2011). Essential role for Abi1 in embryonic survival and WAVE2 complex integrity. Proc. Natl. Acad. Sci. U.S.A. 108, 7022-7027. doi: 10.1073/pnas.1016811108
32. Eden, S., Rohatgi, R., Podtelejnikov, A. V., Mann, M., and Kirschner, M. W. (2002). Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck. Nature 418, 790-793. doi: 10.1038/nature00859.
33. Feng, Y., Absher, D., Eberhart, D. E., Brown, V., Malter, H. E., and Warren, S. T. (1997). Fmrp associates with polyribosomes as an mRNP, and the I304N mutation ofseverefragileXsyndromeabolishesthisassociation. Mol. Cell. 1, 109-118. doi: 10.1016/S1097-2765(00)80012-X
34. Fromer, M., Poclington, A. J., Kavanagh, D. H., Williams, H. J., Dwyer, S., Gormley, P., et al. (2014). De novo mutations in schizophrenia implicate synaptic networks. Nature. doi: 10.1038/nature12929 [Epub ahead of print].
35. Gautier, J. J., Lomakina, M. E., Bouslama-Oueghlani, L., Derivery, E., Beilinson, H., Faigle, W., et al. (2011). Clathrin is required for Scar/Wave-mediated lamellipodium formation. J. Cell Sci. 124, 3414-3427. doi: 10.1242/jcs.081083.
36. Gilman, S. R., Iossifov, I., Levy, D., Ronemus, M., Wigler, M., andVitkup, D. (2011). Rare de novo variants associated with autism implicate a large functional network of genes involved in formation and function of synapses. Neuron 70, 898-907. doi: 10.1016/j.neuron.2011.05.021.
37. Giuffrida, R., Musumeci, S., D'antoni, S., Bonaccorso, C. M., Giuffrida-Stella, A. M., Oostra, B. A., et al. (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, 8908-8916. doi: 10.1523/JNEUR0SCI.0932-05.2005
38. Hashimoto, S., Boissel, S., Zarhrate, M., Rio, M., Munnich, A., Egly, J. M., et al. (2011). MED23 mutation links intellectual disability to dysreg-ulation of immediate early gene expression. Science 333, 1161-1163. doi: 10.1126/science.1206638.
39. Hazai, D., Szudoczki, R., Ding, J., Soderling, S. H., Weinberg, R. J., Sotonyi, P., et al. (2013). Ultrastructural Abnormalities in CA1. Hippocampus Caused by Deletion of the Actin Regulator WAVE-1. PLoS ONE 8:e75248. doi: 10.1371/journal.pone.0075248.
40. Huber, K. M., Gallagher, S. M., Warren, S. T., andBear, M. F. (2002).Alteredsynaptic plasticity in a mouse model of fragile X mental retardation., Proc. Natl. Acad. Sci. U.S.A. 99, 7746-7750. doi: 10.1073/pnas.122205699.
41. Iacoangeli, A., Rozhdestvensky, T. S., Dolzhanskaya, N., Tournier, B., Schutt, J., Brosius, J., et al. (2008a). On BC1. RNA and the fragile X mental retardation protein. Proc.Natl.Acad. Sci. U.S.A. 105, 734-739. doi: 10.1073/pnas.0710991105.
42. Iacoangeli, A., Rozhdestvensky, T. S., Dolzhanskaya, N., Tournier, B., Schutt, J., Brosius, J., et al. (2008b). Reply to Bagni: On BC1. RNA and the fragile X mental retardation protein. Proc. Natl. Acad. Sci. U.S.A. 105, E29. doi: 10.1073/pnas.0803737105.
43. Ingason, A., Kirov, G., Giegling, I., Hansen, T., Isles, A. R., Jakobsen, K. D., et al. (2011). Maternally derived microduplications at 15q11-q13: implication of imprinted genes in psychotic illness. Am. J. Psychiatry 168, 408-417. doi: 10.1176/appi.ajp.2010.09111660.
44. 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. doi: 10.1093/cercor/10.10.1038.
45. Irwin, S. A., Idupulapati, M., Gilbert, M. E., Harris, J. B., Chakravarti, A. B., Rogers, E. J., et al. (2002). Dendritic spine and dendritic field characteristics of layer V pyramidal neurons in the visual cortex of fragile-X knockout mice. Am. J. Med. Genet. 111, 140-146. doi: 10.1002/ajmg.10500.
46. Kawano, Y., Yoshimura, T., Tsuboi, D., Kawabata, S., Kaneko-Kawano, T., Shirataki, H., et al. (2005). CRMP-2 is involved in kinesin-1-dependent transport of the Sra-1/WAVE1 complex and axon formation. Mol. Cell. Biol. 25, 9920-9935. doi: 10.1128/MCB.25.22.9920-9935.2005.
47. Khandjian, E. W., Huot, M. E., Tremblay, S., Davidovic, L., Mazroui, R., and Bardoni, B. (2004). Biochemical evidence for the association of fragile X mental retardation protein with brain polyribosomal ribonucleoparti-cles. Proc. Natl. Acad. Sci. U.S.A. 101, 13357-13362. doi: 10.1073/pnas. 0405398101
48. Kirov, G., Grozeva, D., Norton, N., Ivanov, D., Mantripragada, K. K., Holmans, P., et al. (2009). Support for the involvement of large copy number variants in the pathogenesis of schizophrenia. Hum. Mol. Genet. 18, 1497-1503. doi: 10.1093/hmg/ddp043.
49. Koronakis, V., Hume, P. J., Humphreys, D., Liu, T., Horning, O., Jensen, O. N., et al. (2011). WAVE regulatory complex activation by cooperating GTPases Arf and Rac1. Proc. Natl. Acad. Sci. U.S.A. 108, 14449-14454. doi: 10.1073/pnas.1107666108
50. Kunda, P., Craig, G., Dominguez, V., and Baum, B. (2003). Abi, Sra1, and Kette control the stability and localization of SCAR/WAVE to regulate the formation of actin-based protrusions. Curr. Biol. 13, 1867-1875. doi: 10.1016/j.cub.2003.10.005.
51. Lebensohn, A. M., and Kirschner, M. W. (2009). Activation of the WAVE complex by coincident signals controls actin assembly. Mol. Cell. 36, 512-524. doi: 10.1016/j.molcel.2009.10.024.
52. Leblond, C. S., Heinrich, J., Delorme, R., Proepper, C., Betancur, C., Huguet, G., et al. (2012). Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders. PLoS Genet. 8:e1002521. doi: 10.1371/journal.pgen.1002521.
53. Madrigal, I., Rodriguez-Revenga, L., Xuncla, M., and Mila, M. (2012). 15q11.2 microdeletion and FMR1 premutation in a family with intellectual disabilities and autism. Gene 508, 92-95. doi: 10.1016/j.gene.2012. 07.023
54. Maurin, T., Zongaro, S., and Bardoni, B. (2014). Fragile X Syndrome: From molecular pathology to therapy. Neurosci. Biobehav. Rev. doi: 10.1016/j.neubiorev.2014.01.006 [Epub ahead of print].
55. Melko, M., Nguyen, L. S., Shaw, M., Jolly, L., Bardoni, B., Gecz, J., et al. (2013). Loss of FMR2 further emphasizes the link between deregulation of immediate early response genes FOS and JUN and intellectual disability. Hum. Mol. Genet. 22, 2984-2991. doi: 10.1093/hmg/ddt155.
56. Mongroo, P. S., Noubissi, F. K., Cuatrecasas, M., Kalabis, J., King, C. E., Johnstone, C. N., et al. (2011). IMP-1 displays cross-talk with K-Ras and modulates colon cancer cell survival through the novel proapoptotic protein CYFIP2. Cancer Res. 71, 2172-2182. doi: 10.1158/0008-5472.CAN-10-3295.
57. Murdoch, J. D., and State, M. W. (2013). Recent developments in the genetics of autism spectrum disorders. Curr. Opin. Genet. Dev. 23, 310-315. doi: 10.1016/j.gde.2013.02.003.
58. Musumeci, S. A., Bosco, P., Calabrese, G., Bakker, C., De Sarro, G. B., Elia, M., et al. (2000). Audiogenic seizures susceptibility in transgenic mice with fragile X syndrome. Epilepsia 41, 19-23. doi: 10.1111/j.1528-1157.2000. tb01499.x
59. Nakamoto, M., Nalavadi, V., Epstein, M. P., Narayanan, U., Bassell, G. J., and Warren, S. T. (2007). Fragile X mental retardation protein deficiency leads to excessive mGluR5-dependent internalization of AMPA receptors. Proc. Natl. Acad. Sci. U.S.A. 104, 15537-15542. doi: 10.1073/pnas. 0707484104
60. Napoli, I., Mercaldo, V., Boyl, P. P., Eleuteri, B., Zalfa, F., De Rubeis, S., et al. (2008). The fragile X syndrome protein represses activity-dependent translation through CYFIP1, a new 4E-BP. Cell 134, 1042-1054. doi: 10.1016/j.cell.2008. 07.031
61. Nolze, A., Schneider, J., Keil, R., Lederer, M., Huttelmaier, S., Kessels, M. M., et al. (2013). FMRP regulates actin filament organization via the armadillo protein p0071. RNA 19, 1483-1496. doi: 10.1261/rna.037 945.112
62. Nowiki, S. T., Tassone, F., Ono, M. Y., Ferranti, J., Croquette, M. F., Goodlin-Jones, B., et al. (2007). The Prader-Willi phenotype of fragile X syndrome. J. Dev. Behav. Pediatr. 28, 133-138. doi: 10.1097/01.DBP.0000267563.18952.c9.
63. Pavlowsky, A., Chelly, J., and Billuart, P. (2012). Major synaptic signaling pathways involved in intellectual disability. Mol. Psychiatry 17, 663. doi: 10.1038/mp.2012.79
64. Peters, S. U., Horowitz, L., Barbieri-Welge, R., Taylor, J. L., and Hundley, R. J. (2012). Longitudinal follow-up of autism spectrum features and sensory behaviors in Angelman syndrome by deletion class. J. Child Psychol. Psychiatry 53, 152-159. doi: 10.1111/j.1469-7610.2011.02455.x
65. Pittman, A. J., Gaynes, J. A., and Chien, C. B. (2010). nev (cyfip2) is required for retinal lamination and axon guidance in the zebrafish retinotectal system. Dev. Biol. 344, 784-794. doi: 10.1016/j.ydbio.2010.05.512.
66. Purcell, S. M., Moran, J. L., Fromer, M., Rudefer, D., Solovieff, N., Roussos, P., et al. (2014).Apolygenicburden of rare disruptive mutations in schizophrenia. Nature doi: 10.1038/nature12975 [Epub ahead of print].
67. Qurashi, A., Sahin, H. B., Carrera, P., Gautreau, A., Schenck, A., and Giangrande, A. (2007). HSPC300 and its role in neuronal connectivity. Neural Dev. 2, 18. doi: 10.1186/1749-8104-2-18.
68. Saller, E., Tom, E., Brunori, M., Otter, M., Estreicher, A., Mack, D. H., et al. (1999). Increased apoptosis induction by 121F mutant p53. EMBO J. 18, 4424-4437. doi: 10.1093/emboj/18.16.4424
69. 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. doi: 10.1016/S0896-6273(03)00354-4.
70. Schenck, A., Bardoni, B., Moro, A., Bagni, C., and Mandel, J. L. (2001). Ahighly 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. U.S.A. 98, 8844-8849. doi: 10.1073/pnas.151231598.
71. Schenck, A., Qurashi, A., Carrera, P., Bardoni, B., Diebold, C., Schejter, E., et al. (2004).WAVE/SCAR, amultifunctional complex coordinating different aspects of neuronal connectivity. Dev. Biol. 274, 260-270. doi: 10.1016/j.ydbio.2004.07.009.
72. Schwartz, C. E., and Neri, G. (2012). Autism and intellectual disability: two sides of the same coin. Am. J. Med. Genet. C Semin. Med. Genet. 160C, 89-90. doi: 10.1002/ajmg.c.31329.
73. Silva, J. M., Ezhkova, E., Silva, J., Heart, S., Castillo, M., Campos, Y., et al. (2009). Cyfip1 isaputative invasion suppressorinepithelialcancers. Cell 137, 1047-1061. doi: 10.1016/j.cell.2009.04.013.
74. Soderling, S.H., Guire, E.S., Kaech, S., White, J., Zhang, F., Schutz, K., et al. (2007).A WAVE-1 and WRP signaling complex regulates spine density, synaptic plasticity, and memory. J. Neurosci. 27, 355-365. doi: 10.1523/JNEUROSCI.3209-06.2006.
75. Spranger, S., Rommel, B., Jauch, A., Bodammer, R., Mehl, B., and Bullerdiek, J. (2000). Interstitial deletion of 5q33.3q35.1 in a girl with mild mental retardation. Am. J. Med. Genet. 93, 107-109. doi: 10.1002/1096-8628(20000717)93:2<107::AID-AJMG5>3.0.CO;2-8.
76. Stefani, G., Fraser, C. E., Darnell, J. C., and Darnell, R. B. (2004). Fragile X mental retardation protein is associated with translating polyribosomes in neuronal cells. J. Neurosci. 24, 7272-7276. doi: 10.1523/JNEUROSCI. 2306-04.2004
77. Stefansson, H., Rujescu, D., Cichon, S., Pietilainen, O. P., Inga-son, A., Steinberg, S., et al. (2008). Large recurrent microdeletions associated with schizophrenia. Nature 455, 232-236. doi: 10.1038/ nature07229
78. Stefansson, H., Meyer-Lindenberg, A., Steinberg, S., Magnusdottir, B. B., Morgen, K., Arnarsdottir, S., et al. (2014). CNVs conferring risk of autism or schizophrenia affect cognition in controls. Nature 505, 361-366. doi: 10.1038/ nature12818
79. Swanger, S. A., and Bassell, G. J. (2011). Making and breaking synapses through local mRNA regulation. Curr. Opin. Genet. Dev. 21, 414-421. doi: 10.1016/j.gde.2011.04.002.
80. Thomas, A. M., Bui, N., Perkins, J. R., Yuva-Paylor, L. A., and Paylor, R. (2012). Group I metabotropic glutamate receptor antagonists alter select behaviors in a mousemodel forfragileXsyndrome. Psychopharmacology (Berl), 219, 47-58. doi: 10.1007/s00213-011-2375-4.
81. Voineagu, I., and Eapen, V. (2013). Converging pathways in autism spectrum disorders: interplay between synaptic dysfunction and immune responses. Front. Hum. Neurosci. 7:738. doi: 10.3389/fnhum.2013. 00738
82. Willsey, A. J., Sanders, S. J., Li, M., Dong, S., Tebbenkamp, A. T., Muhle, R. A., et al. (2013). Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism. Cell 155, 997-1007. doi: 10.1016/j.cell.2013.10.020.
83. Wilson, B. M., and Cox, C. L. (2007). Absence of metabotropic glutamate receptor-mediated plasticity in the neocortex of fragile X mice. Proc. Natl. Acad. Sci. U.S.A. 104, 2454-2459. doi: 10.1073/pnas. 0610875104
84. Yan, Q. J., Rammal, M., Tranfaglia, M., and Bauchwitz, R. P. (2005). Suppression of two major Fragile X Syndrome mouse model phenotypes by the mGluR5 antagonist MPEP. Neuropharmacology 49, 1053-1066. doi: 10.1016/j.neuropharm.2005.06.004.
85. Zhang, Y. Q., Bailey, A. M., Matthies, H. J., Renden, R. B., Smith, M. A., Speese, S. D., et al. (2001). Drosophila fragile X-related gene regulates the MAP1B homolog Futsch to control synaptic structure and function. Cell 107, 591-603. doi: 10.1016/S0092-8674(01)00589-X
86. Zhao, L., Wang, D., Wang, Q., Rodal, A. A., and Zhang, Y. Q. (2013). Drosophila cyfip regulates synaptic development and endocytosis by suppressing filamentous actin assembly. PLoS Genet. 9:e1003450. doi: 10.1371/journal.pgen. 1003450
87. Zhong, J., Chuang, S. C., Bianchi, R., Zhao, W., Paul, G., Thakkar, P., et al. (2010). Regulatory BC1. RNA and the fragile X mental retardation protein: convergent functionalityin brain. PLoS ONE 5:e15509. doi: 10.1371/journal.pone.0015509