Synapse Formation in the Brain

  • Masayoshi MishinaEmail author
  • Tomoyuki Yoshida
  • Misato Yasumura
  • Takeshi Uemura


Precise synaptic connections between nerve cells in the brain provide the basis of perception, learning, memory, and cognition. Synapse formation is the key step in the development of neuronal networks and requires the coordinate assembly of large numbers of protein complexes. Trans-synaptic cell adhesion molecules are thought to mediate target recognition and induction of pre- and postsynaptic specializations. Despite the wealth of information on the molecular mechanisms of glutamatergic synaptogenesis proposed by in vitro studies using neuronal cell culture models, evidence for their relevance to synaptogenesis in vivo has been lacking. Thus, fundamental questions about how glutamatergic synapses are formed in the mammalian brain have remained unanswered. On the other hand, there is clear in vivo evidence that GluRδ2, a member of the δ-type glutamate receptor (GluR), plays an essential role in cerebellar Purkinje cell (PC) synapse formation. We found that a significant number of PC spines lack synaptic contacts with parallel fiber (PF) terminals and some of residual PF-PC synapses show mismatching between pre- and postsynaptic specializations in conventional and conditional GluRδ2 knockout mice. Recently, we have shown that the trans-synaptic interaction of postsynaptic GluRδ2 and presynaptic neurexins (NRXNs) through Cbln1 mediates PF-PC synapse formation. The assembly stoichiometry of the synaptogenic GluRδ2-Cbln1-NRXN1β triad provides the molecular insight into the mechanism of PF-PC synapse formation in the cerebellum. IL1-receptor accessory protein-like 1 (IL1RAPL1) is responsible for nonsyndromic mental retardation and autism. We have found that postsynaptic IL1RAPL1 mediates excitatory synapse formation of cortical neurons through trans-synaptic interaction with specific variants of presynaptic protein tyrosine phosphatase-δ. These results imply the impaired synapse formation as a common pathogenic pathway shared by mental retardation and autism.


HEK293T Cell Synapse Formation Olfactory Sensory Neuron Staining Signal Presynaptic Active Zone 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported in part by research grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan. We thank Ms. Ryoko Suzuki for help in the preparation of the manuscript.


  1. Abrahams BS, Geschwind DH (2008) Advances in autism genetics: on the threshold of a new neurobiology. Nat Rev Genet 9:341–355PubMedCrossRefGoogle Scholar
  2. Araki K, Meguro H, Kushiya E, Takayama C, Inoue Y, Mishina M (1993) Selective expression of the glutamate receptor channel δ2 subunit in cerebellar Purkinje cells. Biochem Biophys Res Commun 197:1267–1276PubMedCrossRefGoogle Scholar
  3. Bakalyar HA, Reed RR (1990) Identification of a specialized adenylyl cyclase that may mediate odorant detection. Science 250:1403–1406PubMedCrossRefGoogle Scholar
  4. Bao D, Pang Z, Morgan JI (2005) The structure and proteolytic processing of Cbln1 complexes. J Neurochem 95:618–629PubMedCrossRefGoogle Scholar
  5. Berkel S, Marshall CR, Weiss B, Howe J, Roeth R, Moog U, Endris V, Roberts W, Szatmari P, Pinto D, Bonin M, Riess A, Engels H, Sprengel R, Scherer SW, Rappold GA (2010) Mutations in the SHANK2 synaptic scaffolding gene in autism spectrum disorder and mental retardation. Nat Genet 42:489–491PubMedCrossRefGoogle Scholar
  6. Biederer T, Südhof TC (2000) Mints as adaptors: direct binding to neurexins and recruitment of Munc18. J Biol Chem 275:39803–39806PubMedCrossRefGoogle Scholar
  7. Biederer T, Südhof TC (2001) CASK and protein 4.1 support F-actin nucleation on neurexins. J Biol Chem 276:47869–47876PubMedGoogle Scholar
  8. Bill BR, Geschwind DH (2009) Genetic advances in autism: heterogeneity and convergence on shared pathways. Curr Opin Genet Dev 19:271–278PubMedCrossRefGoogle Scholar
  9. Born TL, Smith DE, Garka KE, Renshaw BR, Bertles JS, Sims JE (2000) Identification and characterization of two members of a novel class of the interleukin-1 receptor (IL-1R) family. Delineation of a new class of IL-1R-related proteins based on signaling. J Biol Chem 275:29946–29954PubMedCrossRefGoogle Scholar
  10. Bourgeron T (2009) A synaptic trek to autism. Curr Opin Neurobiol 19:231–234PubMedCrossRefGoogle Scholar
  11. Butz S, Okamoto M, Südhof TC (1998) A tripartite protein complex with the potential to couple synaptic vesicle exocytosis to cell adhesion in brain. Cell 94:773–782PubMedCrossRefGoogle Scholar
  12. Carrié A, Jun L, Bienvenu T et al (1999) A new member of the IL-1 receptor family highly expressed in hippocampus and involved in X-linked mental retardation. Nat Genet 23:25–31PubMedGoogle Scholar
  13. Chelly J, Mandel JL (2001) Monogenic causes of X-linked mental retardation. Nat Rev Genet 2:669–680PubMedCrossRefGoogle Scholar
  14. Chelly J, Khelfaoui M, Francis F, Chérif B, Bienvenu T (2006) Genetics and pathophysiology of mental retardation. Eur J Hum Genet 14:701–713PubMedCrossRefGoogle Scholar
  15. Chen X, Yoshida T, Sagara H, Mikami Y, Mishina M (2011) Protein tyrosine phosphatase σ regulates the synapse number of zebrafish olfactory sensory neurons. J Neurochem 119:532–543PubMedCrossRefGoogle Scholar
  16. Chiurazzi P, Schwartz CE, Gecz J, Neri G (2008) XLMR genes: update 2007. Eur J Hum Genet 16:422–434PubMedCrossRefGoogle Scholar
  17. Dalva MB, McClelland AC, Kayser MS (2007) Cell adhesion molecules: signalling functions at the synapse. Nat Rev Neurosci 8:206–220PubMedCrossRefGoogle Scholar
  18. de Wit J, Sylwestrak E, O’Sullivan ML, Otto S, Tiglio K, Savas JN, Yates JR 3rd, Comoletti D, Taylor P, Ghosh A (2009) LRRTM2 interacts with Neurexin1 and regulates excitatory synapse formation. Neuron 64:799–806PubMedCrossRefGoogle Scholar
  19. Dean C, Scholl FG, Choih J, DeMaria S, Berger J, Isacoff E, Scheiffele P (2003) Neurexin mediates the assembly of presynaptic terminals. Nat Neurosci 6:708–716PubMedCrossRefGoogle Scholar
  20. Dinarello CA (2009) Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol 27:519–550PubMedCrossRefGoogle Scholar
  21. Durand CM, Betancur C, Boeckers TM et al (2007) Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat Genet 39:25–27PubMedCrossRefGoogle Scholar
  22. Dynes JL, Ngai J (1998) Pathfinding of olfactory neuron axons to stereotyped glomerular targets revealed by dynamic imaging in living zebrafish embryos. Neuron 20:1081–1091PubMedCrossRefGoogle Scholar
  23. Fombonne E (1999) The epidemiology of autism: a review. Psychol Med 29:769–786PubMedCrossRefGoogle Scholar
  24. Gilman SR, 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 70:898–907PubMedCrossRefGoogle Scholar
  25. Graf ER, Zhang X, Jin SX, Linhoff MW, Craig AM (2004) Neurexins induce differentiation of GABA and glutamate postsynaptic specializations via neuroligins. Cell 119:1013–1026PubMedCrossRefGoogle Scholar
  26. Greenfeder SA, Nunes P, Kwee L, Labow M, Chizzonite RA, Ju G (1995) Molecular cloning and characterization of a second subunit of the interleukin 1 receptor complex. J Biol Chem 270:13757–13765PubMedCrossRefGoogle Scholar
  27. Grootjans JJ, Reekmans G, Ceulemans H, David G (2000) Syntenin-syndecan binding requires syndecan-synteny and the co-operation of both PDZ domains of syntenin. J Biol Chem 275:19933–19941PubMedCrossRefGoogle Scholar
  28. Hata Y, Davletov B, Petrenko AG, Jahn R, Südhof TC (1993) Interaction of synaptotagmin with the cytoplasmic domains of neurexins. Neuron 10:307–315PubMedCrossRefGoogle Scholar
  29. Hata Y, Butz S, Südhof TC (1996) CASK: a novel dlg/PSD95 homolog with an N-terminal calmodulin-dependent protein kinase domain identified by interaction with neurexins. J Neurosci 16:2488–2494PubMedGoogle Scholar
  30. Hirai H, Pang Z, Bao D, Miyazaki T, Li L, Miura E, Parris J, Rong Y, Watanabe M, Yuzaki M, Morgan JI (2005) Cbln1 is essential for synaptic integrity and plasticity in the cerebellum. Nat Neurosci 8:1534–1541PubMedCrossRefGoogle Scholar
  31. Jamain S, Betancur C, Quach H, Philippe A, Fellous M, Giros B, Gillberg C, Leboyer M, Bourgeron T, Paris Autism Research International Sibpair (PARIS) Study (2003) Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat Genet 34:27–29PubMedCrossRefGoogle Scholar
  32. Joo JY, Lee SJ, Uemura T, Yoshida T, Yasumura M, Watanabe M, Mishina M (2011) Differential interactions of cerebellin precursor protein (Cbln) subtypes and neurexin variants for synapse formation of cortical neurons. Biochem Biophys Res Commun 406:627–632PubMedCrossRefGoogle Scholar
  33. Kashiwabuchi N, Ikeda K, Araki K, Hirano T, Shibuki K, Takayama C, Inoue Y, Kutsuwada T, Yagi T, Kang Y, Aizawa S, Mishina M (1995) Impairment of motor coordination, Purkinje cell synapse formation, and cerebellar long-term depression in GluRδ2 mutant mice. Cell 81:245–252PubMedCrossRefGoogle Scholar
  34. Kim E, Sheng M (2004) PDZ domain proteins of synapses. Nat Rev Neurosci 5:771–781PubMedCrossRefGoogle Scholar
  35. Kim HG, Kishikawa S, Higgins AW et al (2008) Disruption of neurexin1 associated with autism spectrum disorder. Am J Hum Genet 82:199–207PubMedCrossRefGoogle Scholar
  36. Ko J, Fuccillo MV, Malenka RC, Südhof TC (2009) LRRTM2 functions as a neurexin ligand in promoting excitatory synapse formation. Neuron 64:791–798PubMedCrossRefGoogle Scholar
  37. Kurihara H, Hashimoto K, Kano M, Takayama C, Sakimura K, Mishina M, Inoue Y, Watanabe M (1997) Impaired parallel fiber-Purkinje cell synapse stabilization during cerebellar development of mutant mice lacking the glutamate receptor δ2 subunit. J Neurosci 17:9613–9623PubMedGoogle Scholar
  38. Kwon SK, Woo J, Kim SY, Kim H, Kim E (2010) Trans-synaptic adhesions between netrin-G ligand-3 (NGL-3) and receptor tyrosine phosphatases LAR, protein-tyrosine phosphatase δ (PTPδ), and PTPσ via specific domains regulate excitatory synapse formation. J Biol Chem 285:13966–13978PubMedCrossRefGoogle Scholar
  39. Landsend AS, Amiry-Moghaddam M, Matsubara A, Bergersen L, Usami S, Wenthold RJ, Ottersen OP (1997) Differential localization of δ glutamate receptors in the rat cerebellum: coexpression with AMPA receptors in parallel fiber-spine synapses and absence from climbing fiber-spine synapses. J Neurosci 17:834–842PubMedGoogle Scholar
  40. Laumonnier F, Bonnet-Brilhault F, Gomot M, Blanc R, David A, Moizard MP, Raynaud M, Ronce N, Lemonnier E, Calvas P, Laudier B, Chelly J, Fryns JP, Ropers HH, Hamel BC, Andres C, Barthélémy C, Moraine C, Briault S (2004) 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 74:552–557PubMedCrossRefGoogle Scholar
  41. Laumonnier F, Shoubridge C, Antar C, Nguyen LS, Van Esch H, Kleefstra T, Briault S, Fryns JP, Hamel B, Chelly J, Ropers HH, Ronce N, Blesson S, Moraine C, Gécz J, Raynaud M (2010) Mutations of the UPF3B gene, which encodes a protein widely expressed in neurons, are associated with nonspecific mental retardation with or without autism. Mol Psychiatry 15:767–776PubMedCrossRefGoogle Scholar
  42. Lee SJ, Uemura T, Yoshida T, Mishina M (2012) GluRδ2 assembles four neurexins into trans-synaptic triad to trigger synapse formation. J Neurosci 32:4688–4701PubMedCrossRefGoogle Scholar
  43. Levy SE, Mandell DS, Schultz RT (2009) Autism. Lancet 374:1627–1638PubMedCrossRefGoogle Scholar
  44. Levy D, Ronemus M, Yamrom B, Lee YH, Leotta A, Kendall J, Marks S, Lakshmi B, Pai D, Ye K, Buja A, Krieger A, Yoon S, Troge J, Rodgers L, Iossifov I, Wigler M (2011) Rare de novo and transmitted copy-number variation in autistic spectrum disorders. Neuron 70:886–897PubMedCrossRefGoogle Scholar
  45. Li J, Mack JA, Souren M, Yaksi E, Higashijima S, Mione M, Fetcho JR, Friedrich RW (2005) Early development of functional spatial maps in the zebrafish olfactory bulb. J Neurosci 25:5784–5795PubMedCrossRefGoogle Scholar
  46. Lomeli H, Sprengel R, Laurie DJ, Köhr G, Herb A, Seeburg PH, Wisden W (1993) The rat delta-1 and delta-2 subunits extend the excitatory amino acid receptor family. FEBS Lett 315:318–322PubMedCrossRefGoogle Scholar
  47. Lu HL, Yang CY, Chen HC, Hung CS, Chiang YC, Ting LP (2008) A novel alternatively spliced interleukin-1 receptor accessory protein mIL-1RAcP687. Mol Immunol 45:1374–1384PubMedCrossRefGoogle Scholar
  48. Marxen M, Volknandt W, Zimmermann H (1999) Endocytic vacuoles formed following a short pulse of K+-stimulation contain a plethora of presynaptic membrane proteins. Neuroscience 94:985–996PubMedCrossRefGoogle Scholar
  49. Maximov A, Südhof TC, Bezprozvannv I (1999) Association of neuronal calcium channels with modular adaptor proteins. J Biol Chem 274:24453–24456PubMedCrossRefGoogle Scholar
  50. McAllister AK (2007) Dynamic aspects of CNS synapse formation. Annu Rev Neurosci 30:425–450PubMedCrossRefGoogle Scholar
  51. Mishina M, Uemura T, Yasumura M, Yoshida T (2012) Molecular mechanism of parallel fiber-Purkinje cell synapse formation. Front Neural Circuits 6:90PubMedCrossRefGoogle Scholar
  52. Mons N, Guillou JL, Jaffard R (1999) The role of Ca2+/calmodulin-stimulable adenylyl cyclases as molecular coincidence detectors in memory formation. Cell Mol Life Sci 55:525–533PubMedCrossRefGoogle Scholar
  53. Palmer G, Lipsky BP, Smithgall MD, Meininger D, Siu S, Talabot-Ayer D, Gabay C, Smith DE (2008) The IL-1 receptor accessory protein (AcP) is required for IL-33 signaling and soluble AcP enhances the ability of soluble ST2 to inhibit IL-33. Cytokine 42:358–364PubMedCrossRefGoogle Scholar
  54. Pavlowsky A, Gianfelice A, Pallotto M, Zanchi A, Vara H, Khelfaoui M, Valnegri P, Rezai X, Bassani S, Brambilla D, Kumpost J, Blahos J, Roux MJ, Humeau Y, Chelly J, Passafaro M, Giustetto M, Billuart P, Sala C (2010) A postsynaptic signaling pathway that may account for the cognitive defect due to IL1RAPL1 mutation. Curr Biol 20:103–115PubMedCrossRefGoogle Scholar
  55. Pinto D, Pagnamenta AT, Klei L et al (2010) Functional impact of global rare copy number variation in autism spectrum disorders. Nature 466:368–372PubMedCrossRefGoogle Scholar
  56. Piton A, Michaud JL, Peng H, Aradhya S, Gauthier J, Mottron L, Champagne N, Lafrenière RG, Hamdan FF, S2D team, Joober R, Fombonne E, Marineau C, Cossette P, Dubé MP, Haghighi P, Drapeau P, Barker PA, Carbonetto S, Rouleau GA (2008) Mutations in the calcium-related gene IL1RAPL1 are associated with autism. Hum Mol Genet 17:3965–3974PubMedCrossRefGoogle Scholar
  57. Ropers HH (2006) X-linked mental retardation: many genes for a complex disorder. Curr Opin Genet Dev 16:260–269PubMedCrossRefGoogle Scholar
  58. Sala C, Piëch V, Wilson NR, Passafaro M, Liu G, Sheng M (2001) Regulation of dendritic spine morphology and synaptic function by Shank and Homer. Neuron 31:115–130PubMedCrossRefGoogle Scholar
  59. Sanders SJ, Ercan-Sencicek AG, Hus V et al (2011) Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism. Neuron 70:863–885PubMedCrossRefGoogle Scholar
  60. Scheiffele P (2003) Cell-cell signaling during synapse formation in the CNS. Annu Rev Neurosci 26:485–508PubMedCrossRefGoogle Scholar
  61. Scheiffele P, Fan J, Choih J, Fetter R, Serafini T (2000) Neuroligin expressed in nonneuronal cells triggers presynaptic development in contacting axons. Cell 101:657–669PubMedCrossRefGoogle Scholar
  62. Shen K, Scheiffele P (2010) Genetics and cell biology of building specific synaptic connectivity. Annu Rev Neurosci 33:473–507PubMedCrossRefGoogle Scholar
  63. Sheng M, Kim E (2000) The Shank family of scaffold proteins. J Cell Sci 113:1851–1856PubMedGoogle Scholar
  64. Siddiqui TJ, Craig AM (2011) Synaptic organizing complexes. Curr Opin Neurobiol 21:132–143PubMedCrossRefGoogle Scholar
  65. Sims JE, Smith DE (2010) The IL-1 family: regulators of immunity. Nat Rev Immunol 10:89–102PubMedCrossRefGoogle Scholar
  66. Smith DE, Lipsky BP, Russell C, Ketchem RR, Kirchner J, Hensley K, Huang Y, Friedman WJ, Boissonneault V, Plante MM, Rivest S, Sims JE (2009) A central nervous system-restricted isoform of the interleukin-1 receptor accessory protein modulates neuronal responses to interleukin-1. Immunity 30:817–831PubMedCrossRefGoogle Scholar
  67. Südhof TC (2008) Neuroligins and neurexins link synaptic function to cognitive disease. Nature 455:903–911PubMedCrossRefGoogle Scholar
  68. Takahashi H, Arstikaitis P, Prasad T, Bartlett TE, Wang YT, Murphy TH, Craig AM (2011) Postsynaptic TrkC and presynaptic PTPσ function as a bidirectional excitatory synaptic organizing complex. Neuron 69:287–303PubMedCrossRefGoogle Scholar
  69. Takayama C, Nakagawa S, Watanabe M, Mishina M, Inoue Y (1996) Developmental changes in expression and distribution of the glutamate receptor channel δ2 subunit according to the Purkinje cell maturation. Brain Res Dev Brain Res 92:147–155PubMedCrossRefGoogle Scholar
  70. Takeuchi T, Miyazaki T, Watanabe M, Mori H, Sakimura K, Mishina M (2005) Control of synaptic connection by glutamate receptor δ2 in the adult cerebellum. J Neurosci 25:2146–2156PubMedCrossRefGoogle Scholar
  71. Tonks NK (2006) Protein tyrosine phosphatases: from genes, to function, to disease. Nat Rev Mol Cell Biol 7:833–846PubMedCrossRefGoogle Scholar
  72. Uemura T, Mishina M (2008) The amino-terminal domain of glutamate receptor δ2 triggers presynaptic differentiation. Biochem Biophys Res Commun 377:1315–1319PubMedCrossRefGoogle Scholar
  73. Uemura T, Kakizawa S, Yamasaki M, Sakimura K, Watanabe M, Iino M, Mishina M (2007) Regulation of long-term depression and climbing fiber territory by glutamate receptor δ2 at parallel fiber synapses through its C-terminal domain in cerebellar Purkinje cells. J Neurosci 27:12096–12108PubMedCrossRefGoogle Scholar
  74. Uemura T, Lee SJ, Yasumura M, Takeuchi T, Yoshida T, Ra M, Taguchi R, Sakimura K, Mishina M (2010) Trans-synaptic interaction of GluRδ2 and neurexin through Cbln1 mediates synapse formation in the cerebellum. Cell 141:1068–1079PubMedCrossRefGoogle Scholar
  75. Urakubo T, Tominaga-Yoshino K, Ogura A (2003) Non-synaptic exocytosis enhanced in rat cerebellar granule neurons cultured under survival-promoting conditions. Neurosci Res 45:429–436PubMedCrossRefGoogle Scholar
  76. Varoqueaux F, Aramuni G, Rawson RL, Mohrmann R, Missler M, Gottmann K, Zhang W, Südhof TC, Brose N (2006) Neuroligins determine synapse maturation and function. Neuron 51:741–754PubMedCrossRefGoogle Scholar
  77. Voineagu I, Wang X, Johnston P, Lowe JK, Tian Y, Horvath S, Mill J, Cantor RM, Blencowe BJ, Geschwind DH (2011) Transcriptomic analysis of autistic brain reveals convergent molecular pathology. Nature 474:380–384PubMedCrossRefGoogle Scholar
  78. Waites CL, Craig AM, Garner CC (2005) Mechanisms of vertebrate synaptogenesis. Annu Rev Neurosci 28:251–274PubMedCrossRefGoogle Scholar
  79. Williams ME, de Wit J, Ghosh A (2010) Molecular mechanisms of synaptic specificity in developing neural circuits. Neuron 68:9–18PubMedCrossRefGoogle Scholar
  80. Wilson SW, Ross LS, Parrett T, Easter SSJ (1990) The development of a simple scaffold of axon tracts in the brain of the embryonic zebrafish, Brachydanio rerio. Development 108:121–145PubMedGoogle Scholar
  81. Woo J, Kwon SK, Choi S, Kim S, Lee JR, Dunah AW, Sheng M, Kim E (2009) Trans-synaptic adhesion between NGL-3 and LAR regulates the formation of excitatory synapses. Nat Neurosci 12:428–437PubMedCrossRefGoogle Scholar
  82. Xia Z, Storm DR (1997) Calmodulin-regulated adenylyl cyclases and neuromodulation. Curr Opin Neurobiol 7:391–396PubMedCrossRefGoogle Scholar
  83. Yoshida T, Mishina M (2005) Distinct roles of calcineurin-nuclear factor of activated T-cells and protein kinase A-cAMP response element-binding protein signaling in presynaptic differentiation. J Neurosci 25:3067–3079PubMedCrossRefGoogle Scholar
  84. Yoshida T, Mishina M (2008) Zebrafish orthologue of mental retardation protein IL1RAPL1 regulates presynaptic differentiation. Mol Cell Neurosci 39:218–228PubMedCrossRefGoogle Scholar
  85. Yoshida T, Ito A, Matsuda N, Mishina M (2002) Regulation by protein kinase A switching of axonal pathfinding of zebrafish olfactory sensory neurons through the olfactory placode-olfactory bulb boundary. J Neurosci 22:4964–4972PubMedGoogle Scholar
  86. Yoshida T, Uchida S, Mishina M (2009) Regulation of synaptic vesicle accumulation and axon terminal remodeling during synapse formation by distinct Ca2+ signaling. J Neurochem 111:160–170PubMedCrossRefGoogle Scholar
  87. Yoshida T, Yasumura M, Uemura T, Lee SJ, Ra M, Taguchi R, Iwakura Y, Mishina M (2011) IL-1 receptor accessory protein-like 1 associated with mental retardation and autism mediates synapse formation by trans-synaptic interaction with protein tyrosine phosphatase δ. J Neurosci 31:13485–13499PubMedCrossRefGoogle Scholar
  88. Yoshida T, Shiroshima T, Lee SJ, Yasumura M, Uemura T, Chen X, Iwakura T, Mishina M (2012) Neuronal isoform of an essential subunit of receptors for interleukin-1 family cytokines organizes synaptogenesis in the brain. J Neurosci 32:2588–2600PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2013

Authors and Affiliations

  • Masayoshi Mishina
    • 1
    • 2
    Email author
  • Tomoyuki Yoshida
    • 2
  • Misato Yasumura
    • 2
  • Takeshi Uemura
    • 2
  1. 1.Brain Science Laboratory, The Research Organization of Science and TechnologyRitsumeikan UniversityKusatsuJapan
  2. 2.Department of Molecular Neurobiology and Pharmacology, Graduate School of MedicineUniversity of TokyoTokyoJapan

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