Nrxn1

Summary

Gene Symbol: Nrxn1
Description: neurexin I
Alias: 1700062G21Rik, 9330127H16Rik, A230068P09Rik, mKIAA0578, neurexin-1, alpha-latrotoxin receptor (calcium-dependent), neurexin 1 NRXN1+7a, neurexin 1 NRXN1-7
Species: mouse
Products:     Nrxn1

Top Publications

  1. Grayton H, Missler M, Collier D, Fernandes C. Altered social behaviours in neurexin 1? knockout mice resemble core symptoms in neurodevelopmental disorders. PLoS ONE. 2013;8:e67114 pubmed publisher
    ..3, which have been associated with autism, schizophrenia and mental retardation, affect only the neurexin 1 gene, usually the alpha isoform...
  2. Iijima T, Wu K, Witte H, Hanno Iijima Y, Glatter T, Richard S, et al. SAM68 regulates neuronal activity-dependent alternative splicing of neurexin-1. Cell. 2011;147:1601-14 pubmed publisher
    ..We demonstrate that Nrxn1 alternative splicing is temporally and spatially controlled in the mouse brain...
  3. Dudanova I, Sedej S, Ahmad M, Masius H, Sargsyan V, Zhang W, et al. Important contribution of alpha-neurexins to Ca2+-triggered exocytosis of secretory granules. J Neurosci. 2006;26:10599-613 pubmed
    ..Our data support a general and essential role for alpha-neurexins in Ca2+-triggered exocytosis that is similarly important for secretion from neurons and endocrine cells. ..
  4. Zhang W, Rohlmann A, Sargsyan V, Aramuni G, Hammer R, Sudhof T, et al. Extracellular domains of alpha-neurexins participate in regulating synaptic transmission by selectively affecting N- and P/Q-type Ca2+ channels. J Neurosci. 2005;25:4330-42 pubmed
  5. Tabuchi K, Sudhof T. Structure and evolution of neurexin genes: insight into the mechanism of alternative splicing. Genomics. 2002;79:849-59 pubmed
    ..Consistent with their proposed role in synapse specification, neurexins thus have evolved from relatively simple genes in invertebrates to diversified genes in vertebrates with multiple promoters and extensive alternative splicing. ..
  6. Dean C, Scholl F, Choih J, DeMaria S, Berger J, Isacoff E, et al. Neurexin mediates the assembly of presynaptic terminals. Nat Neurosci. 2003;6:708-16 pubmed
    ..In response to this clustering, neurexins nucleate the assembly of a cytoplasmic scaffold to which the exocytotic apparatus is recruited. ..
  7. Etherton M, Blaiss C, Powell C, Südhof T. Mouse neurexin-1alpha deletion causes correlated electrophysiological and behavioral changes consistent with cognitive impairments. Proc Natl Acad Sci U S A. 2009;106:17998-8003 pubmed publisher
    ..Together, these data indicate that the neurexin-1alpha deficiency induces a discrete neural phenotype whose extent correlates, at least in part, with impairments observed in human patients. ..
  8. Graf E, Zhang X, Jin S, Linhoff M, Craig A. Neurexins induce differentiation of GABA and glutamate postsynaptic specializations via neuroligins. Cell. 2004;119:1013-26 pubmed
  9. Missler M, Zhang W, Rohlmann A, Kattenstroth G, Hammer R, Gottmann K, et al. Alpha-neurexins couple Ca2+ channels to synaptic vesicle exocytosis. Nature. 2003;423:939-48 pubmed
    ..These data suggest that alpha-neurexins organize presynaptic terminals by functionally coupling Ca2+ channels to the presynaptic machinery. ..

More Information

Publications59

  1. Puschel A, Betz H. Neurexins are differentially expressed in the embryonic nervous system of mice. J Neurosci. 1995;15:2849-56 pubmed
    ..These expression profiles are consistent with the hypothesis that the neurexins have a function in early neuronal differentiation and axogenesis. ..
  2. Gauthier J, Siddiqui T, Huashan P, Yokomaku D, Hamdan F, Champagne N, et al. Truncating mutations in NRXN2 and NRXN1 in autism spectrum disorders and schizophrenia. Hum Genet. 2011;130:563-73 pubmed publisher
    ..Copy number variations and deleterious mutations in synaptic organizing proteins including NRXN1 have been associated with these neurodevelopmental disorders, but no such associations have been reported for ..
  3. Reichelt A, Rodgers R, Clapcote S. The role of neurexins in schizophrenia and autistic spectrum disorder. Neuropharmacology. 2012;62:1519-26 pubmed publisher
    ..We review the evidence for the role of neurexin-1? in schizophrenia and ASD, and consider how genetic disruption of neurexin-1? may underpin the neuropathology contributing to these distinct neurodevelopmental disorders. ..
  4. Uemura T, Lee S, Yasumura M, Takeuchi T, Yoshida T, Ra M, et al. Trans-synaptic interaction of GluRdelta2 and Neurexin through Cbln1 mediates synapse formation in the cerebellum. Cell. 2010;141:1068-79 pubmed publisher
    ..These results suggest that GluRdelta2 mediates cerebellar synapse formation by interacting with presynaptic NRXNs through Cbln1. ..
  5. Kattenstroth G, Tantalaki E, Sudhof T, Gottmann K, Missler M. Postsynaptic N-methyl-D-aspartate receptor function requires alpha-neurexins. Proc Natl Acad Sci U S A. 2004;101:2607-12 pubmed
    ..Our data suggest that, in addition to the previously described presynaptic impairments, loss of alpha-neurexins induces postsynaptic changes by a cell-autonomous mechanism. ..
  6. Joo J, Lee S, Uemura T, Yoshida T, Yasumura M, Watanabe M, et al. Differential interactions of cerebellin precursor protein (Cbln) subtypes and neurexin variants for synapse formation of cortical neurons. Biochem Biophys Res Commun. 2011;406:627-32 pubmed publisher
    ..The synaptogenic activities of Cbln1 and Cbln2 were suppressed by the addition of the extracellular domain of NRXN1? to the cortical neuron cultures...
  7. Missler M, Sudhof T. Neurexins: three genes and 1001 products. Trends Genet. 1998;14:20-6 pubmed
    ..This review describes the properties of the neurexin protein family and their potential roles in neuronal cell adhesion and intercellular signaling. ..
  8. Dudanova I, Tabuchi K, Rohlmann A, Sudhof T, Missler M. Deletion of alpha-neurexins does not cause a major impairment of axonal pathfinding or synapse formation. J Comp Neurol. 2007;502:261-74 pubmed
    ..Therefore, alpha-neurexins are not essential for the formation of the vast majority of synapses in vivo but rather regulate the function of these synapses. ..
  9. Andres C, Beeri R, Friedman A, Lev Lehman E, Henis S, Timberg R, et al. Acetylcholinesterase-transgenic mice display embryonic modulations in spinal cord choline acetyltransferase and neurexin Ibeta gene expression followed by late-onset neuromotor deterioration. Proc Natl Acad Sci U S A. 1997;94:8173-8 pubmed
  10. Cheng S, Amici S, Ren X, McKay S, Treuil M, Lindstrom J, et al. Presynaptic targeting of alpha4beta 2 nicotinic acetylcholine receptors is regulated by neurexin-1beta. J Biol Chem. 2009;284:23251-9 pubmed publisher
    ..Our results provide novel insights as to possible mechanisms by which dysfunctional neurexins, through downstream effects on alpha4beta2 AChRs, may contribute to the etiology of these neurological disorders. ..
  11. de la Torre Ubieta L, Won H, Stein J, Geschwind D. Advancing the understanding of autism disease mechanisms through genetics. Nat Med. 2016;22:345-61 pubmed publisher
    ..Despite the challenges, these advances provide a solid foundation for the development of rational, targeted molecular therapies. ..
  12. Comoletti D, Flynn R, Jennings L, Chubykin A, Matsumura T, Hasegawa H, et al. Characterization of the interaction of a recombinant soluble neuroligin-1 with neurexin-1beta. J Biol Chem. 2003;278:50497-505 pubmed
    ..We show here that glycosylation processing of neuroligin, in addition to mRNA splicing and gene selection, contributes to the specificity of the neurexin-beta/neuroligin-1 association. ..
  13. Tobaben S, Sudhof T, Stahl B. Genetic analysis of alpha-latrotoxin receptors reveals functional interdependence of CIRL/latrophilin 1 and neurexin 1 alpha. J Biol Chem. 2002;277:6359-65 pubmed
    ..massive neurotransmitter release from nerve terminals by binding to at least two distinct presynaptic receptors, neurexin 1 alpha and CIRL1/latrophilin1 (CL1)...
  14. Yan Q, Weyn Vanhentenryck S, Wu J, Sloan S, Zhang Y, Chen K, et al. Systematic discovery of regulated and conserved alternative exons in the mammalian brain reveals NMD modulating chromatin regulators. Proc Natl Acad Sci U S A. 2015;112:3445-50 pubmed publisher
    ..Our results highlight previously uncharacterized complexity and evolution in the mammalian brain transcriptome. ..
  15. Schwartzer J, Koenig C, Berman R. Using mouse models of autism spectrum disorders to study the neurotoxicology of gene-environment interactions. Neurotoxicol Teratol. 2013;36:17-35 pubmed publisher
  16. Anderson G, Aoto J, Tabuchi K, Földy C, Covy J, Yee A, et al. β-Neurexins Control Neural Circuits by Regulating Synaptic Endocannabinoid Signaling. Cell. 2015;162:593-606 pubmed publisher
  17. Mosedale M, Egodage S, Calma R, Chi N, Chessler S. Neurexin-1? contributes to insulin-containing secretory granule docking. J Biol Chem. 2012;287:6350-61 pubmed publisher
    ..Neurexin-1? is the only transmembrane component of the docking machinery identified thus far. Our findings provide new insights into the mechanisms of insulin granule docking and exocytosis. ..
  18. Fairless R, Masius H, Rohlmann A, Heupel K, Ahmad M, Reissner C, et al. Polarized targeting of neurexins to synapses is regulated by their C-terminal sequences. J Neurosci. 2008;28:12969-81 pubmed publisher
  19. Saura C, Servián Morilla E, Scholl F. Presenilin/?-secretase regulates neurexin processing at synapses. PLoS ONE. 2011;6:e19430 pubmed publisher
    ..These results suggest that PS regulate the synaptic function and processing of neurexins at glutamatergic synapses, and that impaired neurexin processing by PS may play a role in FAD. ..
  20. Dachtler J, Glasper J, Cohen R, Ivorra J, Swiffen D, Jackson A, et al. Deletion of α-neurexin II results in autism-related behaviors in mice. Transl Psychiatry. 2014;4:e484 pubmed publisher
    ..Our findings demonstrate a causal role for the loss of Nrxn2α in the genesis of autism-related behaviors in mice. ..
  21. Divya T, Lalitha S, Parvathy S, Subashini C, Sanalkumar R, Dhanesh S, et al. Regulation of Tlx3 by Pax6 is required for the restricted expression of Chrnα3 in Cerebellar Granule Neuron progenitors during development. Sci Rep. 2016;6:30337 pubmed publisher
  22. Fukuda M, Mikoshiba K. Characterization of KIAA1427 protein as an atypical synaptotagmin (Syt XIII). Biochem J. 2001;354:249-57 pubmed
    ..Since Syt XIII is expressed in various tissues outside the brain, Syt XIII may be involved in constitutive vesicle transport. ..
  23. Bottos A, Destro E, Rissone A, Graziano S, Cordara G, Assenzio B, et al. The synaptic proteins neurexins and neuroligins are widely expressed in the vascular system and contribute to its functions. Proc Natl Acad Sci U S A. 2009;106:20782-7 pubmed publisher
    ..Our finding strongly supports the idea that even the most complex and plastic events taking place in the nervous system (i.e., synaptic activity) share molecular cues with the vascular system...
  24. Fukuda M, Mikoshiba K. Synaptotagmin-like protein 1-3: a novel family of C-terminal-type tandem C2 proteins. Biochem Biophys Res Commun. 2001;281:1226-33 pubmed
    ..In addition, Slp family proteins are differentially distributed in different mouse tissues and at different developmental stages. ..
  25. Geppert M, Khvotchev M, Krasnoperov V, Goda Y, Missler M, Hammer R, et al. Neurexin I alpha is a major alpha-latrotoxin receptor that cooperates in alpha-latrotoxin action. J Biol Chem. 1998;273:1705-10 pubmed
  26. Laarakker M, Reinders N, Bruining H, Ophoff R, Kas M. Sex-dependent novelty response in neurexin-1? mutant mice. PLoS ONE. 2012;7:e31503 pubmed publisher
    Neurexin-1 alpha (NRXN1?) belongs to the family of cell adhesion molecules (CAMs), which are involved in the formation of neuronal networks and synapses...
  27. Lee S, Uemura T, Yoshida T, Mishina M. GluR?2 assembles four neurexins into trans-synaptic triad to trigger synapse formation. J Neurosci. 2012;32:4688-701 pubmed publisher
    ..Analysis of Cbln1 mutants suggested that the binding sites of GluR?2 and NRXN1? on Cbln1 are differential...
  28. Chen S, Tari P, She K, Haas K. Neurexin-neuroligin cell adhesion complexes contribute to synaptotropic dendritogenesis via growth stabilization mechanisms in vivo. Neuron. 2010;67:967-83 pubmed publisher
  29. Ito Ishida A, Miyazaki T, Miura E, Matsuda K, Watanabe M, Yuzaki M, et al. Presynaptically released Cbln1 induces dynamic axonal structural changes by interacting with GluD2 during cerebellar synapse formation. Neuron. 2012;76:549-64 pubmed publisher
    ..Thus, PF protrusions triggered by Nrx-Cbln1-GluD2 signaling may promote bidirectional maturation of PF-PC synapses by a positive feedback mechanism. ..
  30. Neupert C, Schneider R, Klatt O, Reissner C, Repetto D, Biermann B, et al. Regulated Dynamic Trafficking of Neurexins Inside and Outside of Synaptic Terminals. J Neurosci. 2015;35:13629-47 pubmed publisher
    ..Because their dynamic behavior is highly regulated, for example, by different binding activities, these processes have immediate consequences for the function of Nrxns at synapses. ..
  31. Pettem K, Yokomaku D, Luo L, Linhoff M, Prasad T, Connor S, et al. The specific ?-neurexin interactor calsyntenin-3 promotes excitatory and inhibitory synapse development. Neuron. 2013;80:113-28 pubmed publisher
    ..These results identify calsyntenin-3 as an ?-neurexin-specific binding partner required for normal functional GABAergic and glutamatergic synapse development. ..
  32. Dachtler J, Ivorra J, Rowland T, Lever C, Rodgers R, Clapcote S. Heterozygous deletion of α-neurexin I or α-neurexin II results in behaviors relevant to autism and schizophrenia. Behav Neurosci. 2015;129:765-76 pubmed publisher
    ..Human genetic studies have found heterozygous deletions affecting NRXN1 and NRXN2, encoding α-neurexin I (Nrxn1α) and α-neurexin II (Nrxn2α), in individuals with autism ..
  33. Fu Y, Huang Z. Differential dynamics and activity-dependent regulation of alpha- and beta-neurexins at developing GABAergic synapses. Proc Natl Acad Sci U S A. 2010;107:22699-704 pubmed publisher
    ..NRXs, thus, are intrinsically dynamic but are stabilized by local transmitter release. Such an activity-adjusted adhesion system seems ideally suited to rapidly explore and validate synaptic partners guided by synaptic transmission. ..
  34. Mozhui K, Wang X, Chen J, Mulligan M, Li Z, Ingles J, et al. Genetic regulation of Nrxn1 [corrected] expression: an integrative cross-species analysis of schizophrenia candidate genes. Transl Psychiatry. 2011;1:e25 pubmed publisher
    b>Neurexin 1 (NRXN1) is a large presynaptic transmembrane protein that has complex and variable patterns of expression in the brain. Sequence variants in NRXN1 are associated with differences in cognition, and with schizophrenia and autism...
  35. Matsuda K, Yuzaki M. Cbln family proteins promote synapse formation by regulating distinct neurexin signaling pathways in various brain regions. Eur J Neurosci. 2011;33:1447-61 pubmed publisher
    ..These findings revealed the unique and general roles of Cbln family proteins in mediating the formation and maintenance of synapses not only in the cerebellum but also in various other brain regions. ..
  36. Jang W, Choi S, Jeong J, Park J, Kim S, Seog D. Neuronal cell-surface protein neurexin 1 interaction with multi-PDZ domain protein MUPP1. Biosci Biotechnol Biochem. 2014;78:644-6 pubmed publisher
    ..Using the yeast two-hybrid screening, we found that neurexin 1 interacted with multi-PDZ domain protein 1 (MUPP1) through PDZ domain...
  37. Rabaneda L, Robles Lanuza E, Nieto Gonzalez J, Scholl F. Neurexin dysfunction in adult neurons results in autistic-like behavior in mice. Cell Rep. 2014;8:338-46 pubmed publisher
    ..The defects resulting from disruption of neurexin function after the completion of embryonic and early postnatal development suggest that functional impairment of mature circuits can trigger autism-related phenotypes. ..
  38. Lim S, Kwon S, Lee M, Moon J, Jeong D, Park E, et al. Synapse formation regulated by protein tyrosine phosphatase receptor T through interaction with cell adhesion molecules and Fyn. EMBO J. 2009;28:3564-78 pubmed publisher
  39. Kumar D, Thakur M. Perinatal exposure to bisphenol-A impairs spatial memory through upregulation of neurexin1 and neuroligin3 expression in male mouse brain. PLoS ONE. 2014;9:e110482 pubmed publisher
    ..study investigated the effect of perinatal exposure to BPA on the expression of synaptic proteins neurexin1 (Nrxn1) and neuroligin3 (Nlgn3), dendritic spine density and spatial memory in postnatal male mice...
  40. Heller E, Zhang W, Selimi F, Earnheart J, Slimak M, Santos Torres J, et al. The biochemical anatomy of cortical inhibitory synapses. PLoS ONE. 2012;7:e39572 pubmed publisher
  41. Heine M, Thoumine O, Mondin M, Tessier B, Giannone G, Choquet D. Activity-independent and subunit-specific recruitment of functional AMPA receptors at neurexin/neuroligin contacts. Proc Natl Acad Sci U S A. 2008;105:20947-52 pubmed publisher
    ..Such rapid and activity-independent accumulation of functional AMPARs at neurexin-1beta-induced postsynapses points to a new role of AMPARs in synaptogenesis. ..
  42. Singh S, Stogsdill J, Pulimood N, Dingsdale H, Kim Y, Pilaz L, et al. Astrocytes Assemble Thalamocortical Synapses by Bridging NRX1α and NL1 via Hevin. Cell. 2016;164:183-196 pubmed publisher
    ..Our findings also provide an important mechanistic insight into how mutations in these genes may lead to circuit dysfunction in diseases such as autism. ..
  43. Gorecki D, Szklarczyk A, Lukasiuk K, Kaczmarek L, Simons J. Differential seizure-induced and developmental changes of neurexin expression. Mol Cell Neurosci. 1999;13:218-27 pubmed
  44. Chen C, Liu H, Hsueh Y. TLR3 downregulates expression of schizophrenia gene Disc1 via MYD88 to control neuronal morphology. EMBO Rep. 2017;18:169-183 pubmed publisher
    ..Our study reveals a novel mechanism of TLR3 in regulation of dendritic morphology and provides an explanation for how environmental factors influence mental health. ..
  45. Chen L, Jiang M, Zhang B, Gokce O, Südhof T. Conditional Deletion of All Neurexins Defines Diversity of Essential Synaptic Organizer Functions for Neurexins. Neuron. 2017;94:611-625.e4 pubmed publisher
    ..Thus, neurexins function primarily as context-dependent specifiers of synapses. ..
  46. Kumar D, Thakur M. Age-related expression of Neurexin1 and Neuroligin3 is correlated with presynaptic density in the cerebral cortex and hippocampus of male mice. Age (Dordr). 2015;37:17 pubmed publisher
    Neurexin1 (Nrxn1) and Neuroligin3 (Nlgn3) are cell adhesion proteins, which play an important role in synaptic plasticity that declines with advancing age. However, the expression of these proteins during aging has not been analyzed...
  47. Runkel F, Rohlmann A, Reissner C, Brand S, Missler M. Promoter-like sequences regulating transcriptional activity in neurexin and neuroligin genes. J Neurochem. 2013;127:36-47 pubmed publisher
    ..Here, we started to explore this important aspect because expression of Nrxn1-3 and Nlgn1-3 genes is altered in mice lacking the transcriptional regulator methyl-CpG-binding protein2 (MeCP2)...
  48. Kazdoba T, Leach P, Crawley J. Behavioral phenotypes of genetic mouse models of autism. Genes Brain Behav. 2016;15:7-26 pubmed publisher
    ..Robust, replicated autism-relevant behavioral outcomes in a genetic mouse model lend credence to a causal role for specific gene contributions and downstream biological mechanisms in the etiology of autism. ..
  49. Harrington A, Raissi A, Rajkovich K, Berto S, Kumar J, Molinaro G, et al. MEF2C regulates cortical inhibitory and excitatory synapses and behaviors relevant to neurodevelopmental disorders. elife. 2016;5: pubmed publisher
  50. Sons M, Busche N, Strenzke N, Moser T, Ernsberger U, Mooren F, et al. alpha-Neurexins are required for efficient transmitter release and synaptic homeostasis at the mouse neuromuscular junction. Neuroscience. 2006;138:433-46 pubmed
    ..Our data suggest that alpha-neurexins are required for efficient neurotransmitter release at neuromuscular junctions, and that they may perform a role in the molecular mechanism of synaptic homeostasis at these peripheral synapses. ..