Heterogeneity and convergence: The synaptic pathophysiology of autism

European Journal of Neuroscience

Volumn 39, Issue 7, 2014, Pages 1107-1113

  Baudouin, Stéphane J ^a,b  

^a UNIVERSITY OF BASEL   (Switzerland)

^b CARDIFF UNIVERSITY   (United Kingdom)

Author keywords

Autism spectrum disorders; Genetic mouse models; Metabotropic glutamate receptor type I; Neuroligin; Pathophysiology; Prosap Shank

Indexed keywords

METABOTROPIC RECEPTOR 1; CARRIER PROTEIN; METABOTROPIC RECEPTOR; NERVE CELL ADHESION MOLECULE; NEUROLIGIN 1;

ANIMAL MODEL; ARTICLE; AUTISM; CONCEPTUAL FRAMEWORK; GENE CLUSTER; GENETIC ASSOCIATION; GENETIC MODEL; HUMAN; MOUSE; MOUSE MODEL; NONHUMAN; PATHOPHYSIOLOGY; PHENOTYPE; PRIORITY JOURNAL; PSYCHIATRIC DIAGNOSIS; SYNAPSE; ANIMAL; GENETICS; METABOLISM; PHYSIOLOGY;

ANIMALS; CARRIER PROTEINS; CELL ADHESION MOLECULES, NEURONAL; CHILD DEVELOPMENT DISORDERS, PERVASIVE; HUMANS; RECEPTORS, METABOTROPIC GLUTAMATE; SYNAPSES;

EID: 84898722334     PISSN: 0953816X     EISSN: 14609568     Source Type: Journal    
DOI: 10.1111/ejn.12498     Document Type: Article

References (67)

1. Amaral, D.G., Schumann, C.M. & Nordahl, C.W. (2008) Neuroanatomy of autism. Trends Neurosci., 31, 137-145.
2. Arons, M.H., Thynne, C.J., Grabrucker, A.M., Li, D., Schoen, M., Cheyne, J.E., Boeckers, T.M., Montgomery, J.M. & Garner, C.C. (2012) Autism-associated mutations in ProSAP2/Shank3 impair synaptic transmission and neurexin-neuroligin-mediated transsynaptic signaling. J. Neurosci., 32, 14966-14978.
3. Auerbach, B.D., Osterweil, E.K. & Bear, M.F. (2011) Mutations causing syndromic autism define an axis of synaptic pathophysiology. Nature, 480, 63-68.
4. Bateup, H.S., Takasaki, K.T., Saulnier, J.L., Denefrio, C.L. & Sabatini, B.L. (2011) Loss of Tsc1 in vivo impairs hippocampal mGluR-LTD and increases excitatory synaptic function. J. Neurosci., 31, 8862-8869.
5. Baudouin, S. & Scheiffele, P. (2010) SnapShot: neuroligin-neurexin complexes. Cell, 141, 908.
6. Baudouin, S.J., Gaudias, J., Gerharz, S., Hatstatt, L., Zhou, K., Punnakkal, P., Tanaka, K.F., Spooren, W., Hen, R., De Zeeuw, C.I., Vogt, K. & Scheiffele, P. (2012) Shared synaptic pathophysiology in syndromic and nonsyndromic rodent models of autism. Science, 338, 128-132.
7. Bauman, M.L. & Kemper, T.L. (2005) Neuroanatomic observations of the brain in autism: a review and future directions. Int. J. Dev. Neurosci., 23, 183-187.
8. Bear, M.F., Huber, K.M. & Warren, S.T. (2004) The mGIuR theory of fragile X mental retardation. Trends Neurosci., 27, 370-377.
9. Boeckers, T.M., Kreutz, M.R., Winter, C., Zuschratter, W., Smalla, K.H., Sanmarti-Vila, L., Wex, H., Langnaese, K., Bockmann, J., Garner, C.C. & Gundelfinger, E.D. (1999a) Proline-rich synapse-associated protein-1/cortactin binding protein 1(ProSAP1/CortBP1) is a PDZ-domain protein highly enriched in the postsynaptic density. J. Neurosci., 19, 6506-6518.
10. Boeckers, T.M., Winter, C., Smalla, K.H., Kreutz, M.R., Bockmann, J., Seidenbecher, C., Garner, C.C. & Gundelfinger, E.D. (1999b) Proline-rich synapse-associated proteins ProSAP1 and ProSAP2 interact with synaptic proteins of the SAPAP/GKAP family. Biochem. Bioph. Res. Co., 264, 247-252.
11. Boeckers, T.M., Bockmann, J., Kreutz, M.R. & Gundelfinger, E.D. (2002) ProSAP/Shank proteins - a family of higher order organizing molecules of the postsynaptic density with an emerging role in human neurological disease. J. Neurochem., 81, 903-910.
12. Bourgeron, T. (2009) A synaptic trek to autism. Curr. Opin. Neurobiol., 19, 231-234.
13. Bozdagi, O., Sakurai, T., Papapetrou, D., Wang, X., Dickstein, D.L., Takahashi, N., Kajiwara, Y., Yang, M., Katz, A.M., Scattoni, M.L., Harris, M.J., Saxena, R., Silverman, J.L., Crawley, J.N., Zhou, Q., Hof, P.R. & Buxbaum, J.D. (2010) Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication. Mol. Autism, 1, 15.
14. Budreck, E.C. & Scheiffele, P. (2007) Neuroligin-3 is a neuronal adhesion protein at GABAergic and glutamatergic synapses. Eur. J. Neurosci., 26, 1738-1748.
15. Budreck, E.C., Kwon, O.-B., Jung, J.H., Baudouin, S., Thommen, A., Kim, H.-S., Fukazawa, Y., Harada, H., Tabuchi, K., Shigemoto, R., Scheiffele, P. & Kim, J.-H. (2013) Neuroligin-1 controls synaptic abundance of NMDA-type glutamate receptors through extracellular coupling. Proc. Natl. Acad. Sci. USA, 110, 725-730.
16. Busquets-Garcia, A., Gomis-Gonzalez, M., Guegan, T., Agustin-Pavon, C., Pastor, A., Mato, S., Perez-Samartin, A., Matute, C., de la Torre, R., Dierssen, M., Maldonado, R. & Ozaita, A. (2013) Targeting the endocannabinoid system in the treatment of fragile X syndrome. Nat. Med., 19, 603-607.
17. Cajigas, I.J., Tushev, G., Will, T.J., Dieck, S.T., Fuerst, N. & Schuman, E.M. (2012) The local transcriptome in the synaptic neuropil revealed by deep sequencing and high-resolution imaging. Neuron, 74, 453-466.
18. Chadman, K.K., Gong, S., Scattoni, M.L., Boltuck, S.E., Gandhy, S.U., Heintz, N. & Crawley, J.N. (2008) Minimal aberrant behavioral phenotypes of neuroligin-3 R451C knockin mice. Autism Res., 1, 147-158.
19. Darnell, J.C., Van Driesche, S.J., Zhang, C., Hung, K.Y.S., Mele, A., Fraser, C.E., Stone, E.F., Chen, C., Fak, J.J., Chi, S.W., Licatalosi, D.D., Richter, J.D. & Darnell, R.B. (2011) FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism. Cell, 146, 247-261.
20. Etherton, M., Foeldy, C., Sharma, M., Tabuchi, K., Liu, X., Shamloo, M., Malenka, R.C. & Suedhof, T.C. (2011) Autism-linked neuroligin-3 R451C mutation differentially alters hippocampal and cortical synaptic function. Proc. Natl. Acad. Sci. USA, 108, 13764-13769.
21. Ey, E., Yang, M., Katz, A.M., Woldeyohannes, L., Silverman, J.L., Leblond, C.S., Faure, P., Torquet, N., Le Sourd, A.M., Bourgeron, T. & Crawley, J.N. (2012) Absence of deficits in social behaviors and ultrasonic vocalizations in later generations of mice lacking neuroligin4. Genes Brain Behav., 11, 928-941.
22. Foeldy, C., Malenka, R.C. & Suedhof, T.C. (2013) Autism-associated neuroligin-3 mutations commonly disrupt tonic endocannabinoid signaling. Neuron, 78, 498-509.
23. Gilman, S.R., Iossifov, I., Levy, D., Ronemus, M., Wigler, M. & Vitkup, 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.
24. Gkogkas, C.G., Khoutorsky, A., Ran, I., Rampakakis, E., Nevarko, T., Weatherill, D.B., Vasuta, C., Yee, S., Truitt, M., Dallaire, P., Major, F., Lasko, P., Ruggero, D., Nader, K., Lacaille, J.-C. & Sonenberg, N. (2013) Autism-related deficits via dysregulated eIF4E-dependent translational control. Nature, 493, 371-377.
25. Graf, E.R., Zhang, X.Z., Jin, S.X., Linhoff, M.W. & Craig, A.M. (2004) Neurexins induce differentiation of GABA and glutamate postsynaptic specializations via neuroligins. Cell, 119, 1013-1026.
26. Hoon, M., Soykan, T., Falkenburger, B., Hammer, M., Patrizi, A., Schmidt, K.-F., Sassoe-Pognetto, M., Loewel, S., Moser, T., Taschenberger, H., Brose, N. & Varoqueaux, F. (2011) Neuroligin-4 is localized to glycinergic postsynapses and regulates inhibition in the retina. Proc. Natl. Acad. Sci. USA, 108, 3053-3058.
27. Hou, L.F. & Klann, E. (2004) Activation of the phosphoinositide 3-kinase-akt-mammalian target of rapamycin signaling pathway is required for metabotropic glutamate receptor-dependent long-term depression. J. Neurosci., 24, 6352-6361.
28. Hou, L., Antion, M.D., Hu, D., Spencer, C.M., Paylor, R. & Klann, E. (2006) Dynamic translational and proteasomal regulation of fragile X mental retardation protein controls mGluR-dependent long-term depression. Neuron, 51, 441-454.
29. Huber, K.M., Gallagher, S.M., Warren, S.T. & Bear, M.F. (2002) Altered synaptic plasticity in a mouse model of fragile X mental retardation. Proc. Natl. Acad. Sci. USA, 99, 7746-7750.
30. Iossifov, I., Zheng, T., Baron, M., Gilliam, T.C. & Rzhetsky, A. (2008) Genetic-linkage mapping of complex hereditary disorders to a whole-genome molecular-interaction network. Genome Res., 18, 1150-1162.
31. Jamain, S., Radyushkin, K., Hammerschmidt, K., Granon, S., Boretius, S., Varoqueaux, F., Ramanantsoa, N., Gallego, J., Ronnenberg, A., Winter, D., Frahm, J., Fischer, J., Bourgeron, T., Ehrenreich, H. & Brose, N. (2008) Reduced social interaction and ultrasonic communication in a mouse model of monogenic heritable autism. Proc. Natl. Acad. Sci. USA, 105, 1710-1715.
32. Jiang, Y.-H. & Ehlers, M.D. (2013) Modeling autism by SHANK gene mutations in mice. Neuron, 78, 8-27.
33. Jung, K.-M., Sepers, M., Henstridge, C.M., Lassalle, O., Neuhofer, D., Martin, H., Ginger, M., Frick, A., DiPatrizio, N.V., Mackie, K., Katona, I., Piomelli, D. & Manzoni, O.J. (2012) Uncoupling of the endocannabinoid signalling complex in a mouse model of fragile X syndrome. Nat. Commun., 3, 1080.
34. Kano, M., Hashimoto, K. & Tabata, T. (2008) Type-1 metabotropic glutamate receptor in cerebellar Purkinje cells: a key molecule responsible for long-term depression, endocannabinoid signalling and synapse elimination. Philos. T. Roy. Soc. B., 363, 2173-2186.
35. Lim, S., Naisbitt, S., Yoon, J., Hwang, J.I., Suh, P.G., Sheng, M. & Kim, E. (1999) Characterization of the Shank family of synaptic proteins - Multiple genes, alternative splicing, and differential expression in brain and development. J. Biol. Chem., 274, 29510-29518.
36. McBride, S.M.J., Choi, C.H., Wang, Y., Liebelt, D., Braunstein, E., Ferreiro, D., Sehgal, A., Siwicki, K.K., Dockendorff, T.C., Nguyen, H.T., McDonald, T.V. & Jongens, T.A. (2005) Pharmacological rescue of synaptic plasticity, courtship behavior, and mushroom body defects in a Drosophila model of fragile X syndrome. Neuron, 45, 753-764.
37. Meyer, G., Varoqueaux, F., Neeb, A., Oschlies, M. & Brose, N. (2004) The complexity of PDZ domain-mediated interactions at glutamatergic synapses: a case study on neuroligin. Neuropharmacology, 47, 724-733.
38. Michalon, A., Sidorov, M., Ballard, T.M., Ozmen, L., Spooren, W., Wettstein, J.G., Jaeschke, G., Bear, M.F. & Lindemann, L. (2012) Chronic pharmacological mGlu5 inhibition corrects fragile X in adult mice. Neuron, 74, 49-56.
39. Nalavadi, V.C., Muddashetty, R.S., Gross, C. & Bassell, G.J. (2012) Dephosphorylation-induced ubiquitination and degradation of FMRP in dendrites: a role in immediate early mGluR-stimulated translation. J. Neurosci., 32, 2582-2587.
40. Neale, B.M., Kou, Y., Liu, L., Ma'ayan, A., Samocha, K.E., Sabo, A., Lin, C.-F., Stevens, C., Wang, L.-S., Makarov, V., Polak, P., Yoon, S., Maguire, J., Crawford, E.L., Campbell, N.G., Geller, E.T., Valladares, O., Schafer, C., Liu, H., Zhao, T., Cai, G., Lihm, J., Dannenfelser, R., Jabado, O., Peralta, Z., Nagaswamy, U., Muzny, D., Reid, J.G., Newsham, I., Wu, Y., Lewis, L., Han, Y., Voight, B.F., Lim, E., Rossin, E., Kirby, A., Flannick, J., Fromer, M., Shakir, K., Fennell, T., Garimella, K., Banks, E., Poplin, R., Gabriel, S., DePristo, M., Wimbish, J.R., Boone, B.E., Levy, S.E., Betancur, C., Sunyaev, S., Boerwinkle, E., Buxbaum, J.D., Cook, E.H. Jr., Devlin, B., Gibbs, R.A., Roeder, K., Schellenberg, G.D., Sutcliffe, J.S. & Daly, M.J. (2012) Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature, 485, 242-245.
41. Osterweil, E.K., Krueger, D.D., Reinhold, K. & Bear, M.F. (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, 15616-15627.
42. Peca, J., Feliciano, C., Ting, J.T., Wang, W., Wells, M.F., Venkatraman, T.N., Lascola, C.D., Fu, Z. & Feng, G. (2011) Shank3 mutant mice display autistic-like behaviours and striatal dysfunction. Nature, 472, 437-442.
43. Petralia, R.S., Sans, N., Wang, Y.X. & Wenthold, R.J. (2005) Ontogeny of postsynaptic density proteins at glutamatergic synapses. Mol. Cell. Neurosci., 29, 436-452.
44. Potter, W.B., Basu, T., O'Riordan, K.J., Kirchner, A., Rutecki, P., Burger, C. & Roopra, A. (2013) Reduced juvenile long-term depression in tuberous sclerosis complex is mitigated in adults by compensatory recruitment of mGluR5 and Erk signaling. PLoS Biol., 11, e1001627.
45. Poulopoulos, A., Aramuni, G., Meyer, G., Soykan, T., Hoon, M., Papadopoulos, T., Zhang, M., Paarmann, I., Fuchs, C., Harvey, K., Jedlicka, P., Schwarzacher, S.W., Betz, H., Harvey, R.J., Brose, N., Zhang, W. & Varoqueaux, F. (2009) Neuroligin 2 drives postsynaptic assembly at perisomatic inhibitory synapses through gephyrin and collybistin. Neuron, 63, 628-642.
46. Poulopoulos, A., Soykan, T., Tuffy, L.P., Hammer, M., Varoqueaux, F. & Brose, N. (2012) Homodimerization and isoform-specific heterodimerization of neuroligins. Biochem. J., 446, 321-330.
47. Radyushkin, K., Hammerschmidt, K., Boretius, S., Varoqueaux, F., El-Kordi, A., Ronnenberg, A., Winter, D., Frahm, J., Fischer, J., Brose, N. & Ehrenreich, H. (2009) Neuroligin-3-deficient mice: model of a monogenic heritable form of autism with an olfactory deficit. Genes Brain Behav., 8, 416-425.
48. Sakai, Y., Shaw, C.A., Dawson, B.C., Dugas, D.V., Al-Mohtaseb, Z., Hill, D.E. & Zoghbi, H.Y. (2011) Protein interactome reveals converging molecular pathways among autism disorders. Sci. Transl. Med., 3, 86ra49.
49. Schmeisser, M.J., Ey, E., Wegener, S., Bockmann, J., Stempel, A.V., Kuebler, A., Janssen, A.-L., Udvardi, P.T., Shiban, E., Spilker, C., Balschun, D., Skryabin, B.V., Dieck, S.T., Smalla, K.-H., Montag, D., Leblond, C.S., Faure, P., Torquet, N., Le Sourd, A.-M., Toro, R., Grabrucker, A.M., Shoichet, S.A., Schmitz, D., Kreutz, M.R., Bourgeron, T., Gundelfinger, E.D. & Boeckers, T.M. (2012) Autistic-like behaviours and hyperactivity in mice lacking ProSAP1/Shank2. Nature, 486, 256-260.
50. Sharma, A., Hoeffer, C.A., Takayasu, Y., Miyawaki, T., McBride, S.M., Klann, E. & Zukin, R.S. (2010) Dysregulation of mTOR signaling in fragile X syndrome. J. Neurosci., 30, 694-702.
51. Sheng, M. & Kim, E. (2000) The Shank family of scaffold proteins. J. Cell Sci., 113, 1851-1856.
52. Silverman, J.L., Yang, M., Lord, C. & Crawley, J.N. (2010) Behavioural phenotyping assays for mouse models of autism. Nat. Rev. Neurosci., 11, 490-502.
53. Song, J.Y., Ichtchenko, K., Sudhof, T.C. & Brose, N. (1999) Neuroligin 1 is a postsynaptic cell-adhesion molecule of excitatory synapses. Proc. Natl. Acad. Sci. USA, 96, 1100-1105.
54. Sudhof, T.C. (2008) Neuroligins and neurexins link synaptic function to cognitive disease. Nature, 455, 903-911.
55. Tabuchi, K., Blundell, J., Etherton, M.R., Hammer, R.E., Liu, X., Powell, C.M. & Suedhof, T.C. (2007) Neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice. Science, 318, 71-76.
56. Takeuchi, K., Gertner, M.J., Zhou, J., Parada, L.F., Bennett, M.V.L. & Zukin, R.S. (2013) Dysregulation of synaptic plasticity precedes appearance of morphological defects in a Pten conditional knockout mouse model of autism. Proc. Natl. Acad. Sci. USA, 110, 4738-4743.
57. Tsai, P.T., Hull, C., Chu, Y., Greene-Colozzi, E., Sadowski, A.R., Leech, J.M., Steinberg, J., Crawley, J.N., Regehr, W.G. & Sahin, M. (2012) Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice. Nature, 488, 647-651.
58. Varoqueaux, F., Jamain, S. & Brose, N. (2004) Neuroligin 2 is exclusively localized to inhibitory synapses. Eur. J. Cell Biol., 83, 449-456.
59. Varoqueaux, F., Aramuni, G., Rawson, R.L., Mohrmann, R., Missler, M., Gottmann, K., Zhang, W., Suedhof, T.C. & Brose, N. (2006) Neuroligins determine synapse maturation and function. Neuron, 51, 741-754.
60. Verpelli, C., Dvoretskova, E., Vicidomini, C., Rossi, F., Chiappalone, M., Schoen, M., Di Stefano, B., Mantegazza, R., Broccoli, V., Boeckers, T.M., Dityatev, A. & Sala, C. (2011) Importance of Shank3 protein in regulating metabotropic glutamate receptor 5 (mGluR5) expression and signaling at synapses. J. Biol. Chem., 286, 34839-34850.
61. Voineagu, I., Wang, X., Johnston, P., Lowe, J.K., Tian, Y., Horvath, S., Mill, J., Cantor, R.M., Blencowe, B.J. & Geschwind, D.H. (2011) Transcriptomic analysis of autistic brain reveals convergent molecular pathology. Nature, 474, 380.
62. Wang, X., McCoy, P.A., Rodriguiz, R.M., Pan, Y., Je, H.S., Roberts, A.C., Kim, C.J., Berrios, J., Colvin, J.S., Bousquet-Moore, D., Lorenzo, I., Wu, G., Weinberg, R.J., Ehlers, M.D., Philpot, B.D., Beaudet, A.L., Wetsel, W.C. & Jiang, Y.-H. (2011) Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3. Hum. Mol. Genet., 20, 3093-3108.
63. Won, H., Lee, H.-R., Gee, H.Y., Mah, W., Kim, J.-I., Lee, J., Ha, S., Chung, C., Jung, E.S., Cho, Y.S., Park, S.-G., Lee, J.-S., Lee, K., Kim, D., Bae, Y.C., Kaang, B.-K., Lee, M.G. & Kim, E. (2012) Autistic-like social behaviour in Shank2-mutant mice improved by restoring NMDA receptor function. Nature, 486, 261-265.
64. Xu, J.-Y., Xia, Q.-Q. & Xia, J. (2012) A review on the current neuroligin mouse models. Sheng Li Xue Bao, 64, 550-562.
65. Yang, M., Bozdagi, O., Scattoni, M.L., Woehr, M., Roullet, F.I., Katz, A.M., Abrams, D.N., Kalikhman, D., Simon, H., Woldeyohannes, L., Zhang, J.Y., Harris, M.J., Saxena, R., Silverman, J.L., Buxbaum, J.D. & Crawley, J.N. (2012) Reduced excitatory neurotransmission and mild autism-relevant phenotypes in adolescent Shank3 null mutant mice. J. Neurosci., 32, 6525-6541.
66. Zhang, Y.Q., Bailey, A.M., Matthies, H.J.G., Renden, R.B., Smith, M.A., Speese, S.D., Rubin, G.M. & Broadie, K. (2001) Drosophila fragile X-related gene regulates the MAP1B homolog Futsch to control synaptic structure and function. Cell, 107, 591-603.
67. Zhang, C., Zhang, Z., Castle, J., Sun, S., Johnson, J., Krainer, A.R. & Zhang, M.Q. (2008) Defining the regulatory network of the tissue-specific splicing factors Fox-1 and Fox-2. Gene. Dev., 22, 2550-2563.