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Neuroligins and neurexins link synaptic function to cognitive disease

Abstract

The brain processes information by transmitting signals at synapses, which connect neurons into vast networks of communicating cells. In these networks, synapses not only transmit signals but also transform and refine them. Neurexins and neuroligins are synaptic cell-adhesion molecules that connect presynaptic and postsynaptic neurons at synapses, mediate signalling across the synapse, and shape the properties of neural networks by specifying synaptic functions. In humans, alterations in genes encoding neurexins or neuroligins have recently been implicated in autism and other cognitive diseases, linking synaptic cell adhesion to cognition and its disorders.

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Figure 1: Architecture of the trans-synaptic neurexin–neuroligin complex.
Figure 2: Atomic model of the trans-synaptic complex formed by NRXN1β and NLGN1.
Figure 3: Differential effects of deletion of the gene encoding NLGN1 and NLGN2 on inhibitory synapses in the somatosensory cortex.
Figure 4: The Arg451Cys substitution in NLGN3 impairs NLGN3 synthesis but enhances inhibitory synaptic transmission.

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References

  1. Cowan, W. M., Südhof, T. C. & Stevens, C. F. (eds) Synapses (Johns Hopkins Univ. Press, 2000).

    Google Scholar 

  2. Rozov, A., Burnashev, N., Sakmann, B. & Neher, E. Transmitter release modulation by intracellular Ca2+ buffers in facilitating and depressing nerve terminals of pyramidal cells in layer 2/3 of the rat neocortex indicates a target cell-specific difference in presynaptic calcium dynamics. J. Physiol. (Lond.) 531, 807–826 (2001).

    Article  CAS  Google Scholar 

  3. Dityatev, A. & El-Husseini, A. (eds) Molecular Mechanisms of Synaptogenesis (Springer, 2006).

    Book  Google Scholar 

  4. Abbott, L. F. & Regehr, W. G. Synaptic computation. Nature 431, 796–803 (2004).

    Article  ADS  CAS  PubMed  Google Scholar 

  5. Linkenhoker, B. A., von der Ohe, C. G. & Knudsen, E. I. Anatomical traces of juvenile learning in the auditory system of adult barn owls. Nature Neurosci. 8, 93–98 (2005).

    Article  CAS  PubMed  Google Scholar 

  6. Arikkath, J. & Reichardt, L. F. Cadherins and catenins at synapses: roles in synaptogenesis and synaptic plasticity. Trends Neurosci. doi:10.1016/j.tins.2008.07.001 (2008).

  7. Salinas, P. C. & Zou, Y. Wnt signaling in neural circuit assembly. Annu. Rev. Neurosci. 31, 339–358 (2008).

    Article  CAS  PubMed  Google Scholar 

  8. Craig, A. M. & Kang, Y. Neurexin–neuroligin signaling in synapse development. Curr. Opin. Neurobiol. 17, 43–52 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Dean, C. & Dresbach, T. Neuroligins and neurexins: linking cell adhesion, synapse formation and cognitive function. Trends Neurosci. 29, 21–29 (2006).

    Article  CAS  PubMed  Google Scholar 

  10. Missler, M. et al. α-Neurexins couple Ca2+ channels to synaptic vesicle exocytosis. Nature 423, 939–948 (2003). This paper shows that deletion of genes encoding α-NRXNs in mice causes a lethal presynaptic release phenotype and a loss of presynaptic Ca2+-channel function.

    Article  ADS  CAS  PubMed  Google Scholar 

  11. Varoqueaux, F. et al. Neuroligins determine synapse maturation and function. Neuron 51, 741–754 (2006). This paper describes mice lacking NLGN1, NLGN2 and NLGN3, demonstrating that deletion of the genes encoding NLGNs is lethal because it results in impaired synaptic transmission and not a decrease in synapse numbers.

    Article  CAS  PubMed  Google Scholar 

  12. Chubykin, A. A. et al. Activity-dependent validation of excitatory vs. inhibitory synapses by neuroligin-1 vs. neuroligin-2. Neuron 54, 919–931 (2007). This paper demonstrates that the enhancement of synaptic transmission by overexpressed NLGN1 depends on NMDA-receptor signalling.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Feng, J. et al. High frequency of neurexin 1β signal peptide structural variants in patients with autism. Neurosci. Lett. 409, 10–13 (2006).

    Article  CAS  PubMed  Google Scholar 

  14. Szatmari, P. et al. Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nature Genet. 39, 319–328 (2007).

    Article  CAS  PubMed  Google Scholar 

  15. Kim, H. G. et al. Disruption of neurexin 1 associated with autism spectrum disorder. Am. J. Hum. Genet. 82, 199–207 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Yan, J. et al. Neurexin 1α structural variants associated with autism. Neurosci. Lett. doi:10.1016/j.neulet.2008.04.074 (2008).

  17. Zahir, F. R. et al. A patient with vertebral, cognitive and behavioural abnormalities and a de novo deletion of NRXN1α. J. Med. Genet. 45, 239–243 (2008).

    Article  CAS  PubMed  Google Scholar 

  18. Marshall, C. R. Structural variation of chromosomes in autism spectrum disorder. Am. J. Hum. Genet. 82, 477–488 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kirov, G. Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia. Hum. Mol. Genet. 17, 458–465 (2008).

    Article  CAS  PubMed  Google Scholar 

  20. Walsh, T. et al. Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science 320, 539–543 (2008).

    Article  ADS  CAS  PubMed  Google Scholar 

  21. Jamain, S. et al. Mutations of the X-linked genes encoding Nlgns NLGN3 and NLGN4 are associated with autism. Nature Genet. 34, 27–29 (2003). This paper describes the first mutations in the genes that encode NLGNs in patients with familial ASD, initiating a search for mutations in other families in NLGNs or their associated molecules.

    Article  CAS  PubMed  Google Scholar 

  22. Laumonnier, F. et al. X-linked mental retardation and autism are associated with a mutation in the NLGN4 gene, a member of the neuroligin family. Am. J. Hum. Genet. 74, 552–527 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Yan, J. et al. Analysis of the neuroligin 3 and 4 genes in autism and other neuropsychiatric patients. Mol. Psychiatry 10, 329–332 (2005).

    Article  CAS  PubMed  Google Scholar 

  24. Talebizadeh, Z. et al. Novel splice isoforms for NLGN3 and NLGN4 with possible implications in autism. J. Med. Genet. 43, e21 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Chocholska, S., Rossier, E., Barbi, G. & Kehrer-Sawatzki, H. Molecular cytogenetic analysis of a familial interstitial deletion Xp22.2–22.3 with a highly variable phenotype in female carriers. Am. J. Med. Genet. A 140, 604–610 (2006).

    Article  PubMed  CAS  Google Scholar 

  26. Lawson-Yuen, A., Saldivar, J. S., Sommer, S. & Picker, J. Familial deletion within NLGN4 associated with autism and Tourette syndrome. Eur. J. Hum. Genet. 16, 614–618 (2008).

    Article  CAS  PubMed  Google Scholar 

  27. Macarov, M. et al. Deletions of VCX-A and NLGN4: a variable phenotype including normal intellect. J. Intellect. Disabil. Res. 51, 329–333 (2007).

    Article  CAS  PubMed  Google Scholar 

  28. Ushkaryov, Y. A., Rohou, A. & Sugita, S. α-Latrotoxin and its receptors. Handb. Exp. Pharmacol. 184, 171–206 (2008).

    Article  CAS  Google Scholar 

  29. Ushkaryov, Y. A., Petrenko, A. G., Geppert, M. & Südhof, T. C. Neurexins: synaptic cell surface proteins related to the α-latrotoxin receptor and laminin. Science 257, 50–56 (1992). This paper reports the discovery of NRXNs as presynaptic α-latrotoxin receptors.

    Article  ADS  CAS  PubMed  Google Scholar 

  30. Missler, M. & Südhof, T. C. Neurexins: three genes and 1001 products. Trends Genet. 14, 20–25 (1998).

    Article  CAS  PubMed  Google Scholar 

  31. Peles, E. & Salzer, J. L. Molecular domains of myelinated axons. Curr. Opin. Neurobiol. 10, 558–565 (2000).

    Article  CAS  PubMed  Google Scholar 

  32. Tabuchi, K. & Südhof, T. C. Structure and evolution of neurexin genes: insight into the mechanism of alternative splicing. Genomics 79, 849–859 (2002).

    Article  CAS  PubMed  Google Scholar 

  33. Ullrich, B., Ushkaryov, Y. A. & Südhof, T. C. Cartography of neurexins: more than 1000 isoforms generated by alternative splicing and expressed in distinct subsets of neurons. Neuron 14, 497–507 (1995).

    Article  CAS  PubMed  Google Scholar 

  34. Rozic-Kotliroff, G. & Zisapel, N. Ca2+-dependent splicing of neurexin IIα. Biochem. Biophys. Res. Commun. 352, 226–230 (2007).

    Article  CAS  PubMed  Google Scholar 

  35. Ushkaryov, Y. A. & Südhof, T. C. Neurexin IIIα: Extensive alternative splicing generates membrane-bound and soluble forms in a novel neurexin. Proc. Natl Acad. Sci. USA 90, 6410–6414 (1993).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  36. Sugita, S., Khvotchev, M. & Südhof, T. C. Neurexins are functional α-latrotoxin receptors. Neuron 22, 489–496 (1999).

    Article  CAS  PubMed  Google Scholar 

  37. Berninghausen, O. et al. Neurexin Iβ and neuroligin are localized on opposite membranes in mature central synapses. J. Neurochem. 103, 1855–1863 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Chubykin, A. A. et al. Dissection of synapse induction by neuroligins: effect of a neuroligin mutation associated with autism. J. Biol. Chem. 280, 22365–22374 (2005).

    Article  CAS  PubMed  Google Scholar 

  39. Kattenstroth, G., Tantalaki, E., Südhof, T. C., Gottmann, K. & Missler, M. Postsynaptic N-methyl-d-aspartate receptor function requires α-neurexins. Proc. Natl Acad. Sci. USA 101, 2607–2612 (2004).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  40. Taniguchi, H. et al. Silencing of neuroligin function by postsynaptic neurexins. J. Neurosci. 27, 2815–2824 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Ichtchenko, K. et al. Neuroligin 1: a splice-site specific ligand for α-neurexins. Cell 81, 435–443 (1995). This paper includes the identification of NLGNs as postsynaptic NRXN ligands.

    Article  CAS  PubMed  Google Scholar 

  42. Petrenko, A. G. et al. Structure and evolution of neurexophilin. J. Neurosci. 16, 4360–4369 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Sugita, S. et al. A stoichiometric complex of neurexins and dystroglycan in brain. J. Cell Biol. 154, 435–445 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Ichtchenko, K., Nguyen, T. & Südhof, T. C. Structures, alternative splicing, and neurexin binding of multiple neuroligins. J. Biol. Chem. 271, 2676–2682 (1996).

    Article  CAS  PubMed  Google Scholar 

  45. Boucard, A., Chubykin, A. A., Comoletti, D., Taylor, P. & Südhof, T. C. A splice-code for trans-synaptic cell adhesion mediated by binding of neuroligin 1 to α- and β-neurexins. Neuron 48, 229–236 (2005).

    Article  CAS  PubMed  Google Scholar 

  46. Rissone, A. et al. Comparative genome analysis of the neurexin gene family in Danio rerio: insights into their functions and evolution. Mol. Biol. Evol. 24, 236–252 (2007).

    Article  CAS  PubMed  Google Scholar 

  47. Bolliger, M. F. et al. Unusually rapid evolution of neuroligin-4 in mice. Proc. Natl Acad. Sci. USA 105, 6421–6426 (2008).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  48. Song, J.-Y., Ichtchenko, K., Südhof, T. C. & Brose, N. Neuroligin 1 is a postsynaptic cell-adhesion molecule of excitatory synapses. Proc. Natl Acad. Sci. USA 96, 1100–1125 (1999).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  49. Varoqueaux, F., Jamain, S. & Brose, N. Neuroligin 2 is exclusively localized to inhibitory synapses. Eur. J. Cell Biol. 83, 449–456 (2004).

    Article  CAS  PubMed  Google Scholar 

  50. Graf, E. R., Zhang, X., Jin, S. X., Linhoff, M. W. & Craig, A. M. Neurexins induce differentiation of GABA and glutamate postsynaptic specializations via neuroligins. Cell 119, 1013–1026 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Budreck, E. C. & Scheiffele, P. Neuroligin-3 is a neuronal adhesion protein at GABAergic and glutamatergic synapses. Eur. J. Neurosci. 26, 1738–1748 (2007).

    Article  PubMed  Google Scholar 

  52. Comoletti, D. et al. Gene selection, alternative splicing, and post-translational processing regulate neuroligin selectivity for β-neurexins. Biochemistry 45, 12816–12827 (2006).

    Article  CAS  PubMed  Google Scholar 

  53. Chih, B., Gollan, L. & Scheiffele, P. Alternative splicing controls selective trans-synaptic interactions of the neuroligin–neurexin complex. Neuron 51, 171–178 (2006).

    Article  CAS  PubMed  Google Scholar 

  54. Fabrichny, I. P. et al. Structural analysis of the synaptic protein neuroligin and its β-neurexin complex: determinants for folding and cell adhesion. Neuron 56, 979–991 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Arac, D. et al. Structures of neuroligin-1 complex reveal specific protein–protein and protein–Ca2+ interactions. Neuron 56, 992–1003 (2007).

    Article  CAS  PubMed  Google Scholar 

  56. Chen, X., Liu, H., Shim, A. H., Focia, P. J. & He, X. Structural basis for synaptic adhesion mediated by neuroligin–neurexin interactions. Nature Struct. Mol. Biol. 15, 50–56 (2008).References 54 56 report the first atomic structures of the neuroligin–neurexin complex.

    Article  CAS  Google Scholar 

  57. Shen, K. C. et al. Regulation of neurexin 1β tertiary structure and ligand binding through alternative splicing. Structure 16, 422–431 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Koehnke, J. et al. Crystal structures of β-neurexin 1 and β-neurexin 2 ectodomains and dynamics of splice insertion sequence 4. Structure 16, 410–421 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Hata, Y., Butz, S. & Südhof, T. C. CASK: a novel dlg/PSD95 homologue with an N-terminal CaM kinase domain identified by interaction with neurexins. J. Neurosci. 16, 2488–2494 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Biederer, T. & Südhof, T. C. CASK and protein 4.1 support F-actin nucleation on neurexins. J. Biol. Chem. 276, 47869–47876 (2001).

    Article  CAS  PubMed  Google Scholar 

  61. Mukherjee, K. et al. CASK functions as a neurexin-kinase by an unusual mechanism. Cell 133, 328–339 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Butz, S., Okamoto, M. & Südhof, T. C. A tripartite protein complex with the potential to couple synaptic vesicle exocytosis to cell adhesion in brain. Cell 94, 773–782 (1998).

    Article  CAS  PubMed  Google Scholar 

  63. Borg, J. P. et al. Molecular analysis of the X11-mLin-2/CASK complex in brain. J. Neurosci. 19, 1307–1316 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Atasoy, D. et al. Deletion of CASK in mice is lethal and impairs synaptic function. Proc. Natl Acad. Sci. USA 104, 2525–2530 (2007).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  65. Irie, M. et al. Binding of neuroligins to PSD-95. Science 277, 1511–1515 (1997). Together with the finding that NRXNs bind to the MAGUK CASK (ref. 48 ), this paper reveals a quasi-symmetrical design of the NRXN–NLGN junction that contains PSD95 bound to NLGNs postsynaptically.

    Article  CAS  PubMed  Google Scholar 

  66. Sheng, M. & Hoogenraad, C. C. The postsynaptic architecture of excitatory synapses: a more quantitative view. Annu. Rev. Biochem. 76, 823–847 (2007).

    Article  CAS  PubMed  Google Scholar 

  67. Scheiffele, P., Fan, J., Choih, J., Fetter, R. & Serafini, T. Neuroligin expressed in nonneuronal cells triggers presynaptic development in contacting axons. Cell 101, 657–669 (2000). This paper describes the first evidence that NLGNs are not only localized to synapses but also function there, by showing that overexpressed NLGN1 or NLGN2 in a non-neuronal cell can induce co-cultured neurons to form synapses onto that cell.

    Article  CAS  PubMed  Google Scholar 

  68. Nam, C. I. & Chen, L. Postsynaptic assembly induced by neurexin–neuroligin interaction and neurotransmitter. Proc. Natl Acad. Sci. USA 102, 6137–6142 (2005).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  69. Chih, B., Afridi, S. K., Clark, L. & Scheiffele, P. Disorder-associated mutations lead to functional inactivation of neuroligins. Hum. Mol. Genet. 13, 1471–1477 (2004).

    Article  CAS  PubMed  Google Scholar 

  70. Chih, B., Engelman, H. & Scheiffele, P. Control of excitatory and inhibitory synapse formation by neuroligins. Science 307, 1324–1328 (2005).

    Article  ADS  CAS  PubMed  Google Scholar 

  71. Zhang, W. et al. Extracellular domains of α-neurexins participate in regulating synaptic transmission by selectively affecting N-and P/Q-type Ca2+-channels. J. Neurosci. 25, 4330–4342 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Dudanova, I. et al. Important contribution of α-neurexins to Ca2+-triggered exocytosis of secretory granules. J. Neurosci. 26, 10599–10613 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Lord, C., Cook, E. H., Leventhal, B. L. & Amaral, D. G. Autism spectrum disorders. Neuron 28, 355–363 (2000).

    Article  CAS  PubMed  Google Scholar 

  74. Pardo, C. A. & Eberhart, C. G. The neurobiology of autism. Brain Pathol. 7, 434–447 (2007).

    Article  CAS  Google Scholar 

  75. Schmitz, C. & Rezaie, P. The neuropathology of autism: where do we stand? Neuropathol. Appl. Neurobiol. 34, 4–11 (2008).

    CAS  PubMed  Google Scholar 

  76. Courchesne, E. et al. Mapping early brain development in autism. Neuron 56, 399–413 (2007).

    Article  CAS  PubMed  Google Scholar 

  77. Durand, C. M. et al. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nature Genet. 39, 25–37 (2007).

    Article  CAS  PubMed  Google Scholar 

  78. Moessner, R. et al. Contribution of SHANK3 mutations to autism spectrum disorder. Am. J. Hum. Genet. 81, 1289–1297 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Okamoto, N. et al. 22q13 Microduplication in two patients with common clinical manifestations: a recognizable syndrome? Am. J. Med. Genet. A 143A, 2804–2809 (2007).

    Article  CAS  PubMed  Google Scholar 

  80. Manning, M. A. et al. Terminal 22q deletion syndrome: a newly recognized cause of speech and language disability in the autism spectrum. Pediatrics 114, 451–457 (2004).

    Article  PubMed  Google Scholar 

  81. Jeffries, A. R. et al. Molecular and phenotypic characterization of ring chromosome 22. Am. J. Med. Genet. A 137, 139–147 (2005).

    Article  PubMed  Google Scholar 

  82. Wilson, H. L. et al. Molecular characterisation of the 22q13 deletion syndrome supports the role of haploinsufficiency of SHANK3/PROSAP2 in the major neurological symptoms. J. Med. Genet. 40, 575–584 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Tobaben, S., Südhof, T. C. & Stahl, B. The G protein-coupled receptor CL1 interacts directly with proteins of the Shank family. J. Biol. Chem. 275, 36204–36210 (2000).

    Article  CAS  PubMed  Google Scholar 

  84. Morrow, E. M. et al. Identifying autism loci and genes by tracing recent shared ancestry. Science 321, 218–223 (2008).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  85. Comoletti, D. et al. The Arg451Cys-neuroligin-3 mutation associated with autism reveals a defect in protein processing. J. Neurosci. 24, 4889–4893 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Tabuchi, K. et al. A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice. Science 318, 71–76 (2007). This paper describes a mouse model of ASD in which a point mutation found in two brothers with ASD (Arg451Cys in NLGN3) was introduced into mice by homologous recombination.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  87. Jamain, S. et al. Reduced social interaction and ultrasonic communication in a mouse model of monogenic heritable autism. Proc. Natl Acad. Sci. USA 105, 1710–1715 (2008).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  88. Hishimoto, A. et al. Neurexin 3 polymorphisms are associated with alcohol dependence and altered expression of specific isoforms. Hum. Mol. Genet. 16, 2880–2891 (2007).

    Article  CAS  PubMed  Google Scholar 

  89. Lachman, H. M. et al. Genomewide suggestive linkage of opioid dependence to chromosome 14q. Hum. Mol. Genet. 16, 1327–1334 (2007).

    Article  CAS  PubMed  Google Scholar 

  90. Meinrenken, C. J., Borst, J. G. & Sakmann, B. Local routes revisited: the space and time dependence of the Ca2+ signal for phasic transmitter release at the rat calyx of Held. J. Physiol. (Lond.) 547, 665–689 (2003).

    CAS  Google Scholar 

  91. Südhof, T. C. The synaptic vesicle cycle. Annu. Rev. Neurosci. 27, 509–547 (2004).

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

I thank D. Arac, A. Brunger, X. Liu, J. Gibson and K. Huber for advice and help with figures. Work in my laboratory on NRXNs and NLGNs is supported by the National Institute of Mental Health and the Simon Foundation.

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Südhof, T. Neuroligins and neurexins link synaptic function to cognitive disease. Nature 455, 903–911 (2008). https://doi.org/10.1038/nature07456

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