Nrxn1

Summary

Gene Symbol: Nrxn1
Description: neurexin 1
Alias: Nrxn1b, neurexin-1, neurexin I-alpha, neurexin I-beta, neurexin-1-alpha, neurexin-1-beta, non-processed neurexin I-alpha
Species: rat
Products:     Nrxn1

Top Publications

  1. Zweier C, de Jong E, Zweier M, Orrico A, Ousager L, Collins A, et al. CNTNAP2 and NRXN1 are mutated in autosomal-recessive Pitt-Hopkins-like mental retardation and determine the level of a common synaptic protein in Drosophila. Am J Hum Genet. 2009;85:655-66 pubmed publisher
    Heterozygous copy-number variants and SNPs of CNTNAP2 and NRXN1, two distantly related members of the neurexin superfamily, have been repeatedly associated with a wide spectrum of neuropsychiatric disorders, such as developmental ..
  2. 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. ..
  3. Ushkaryov Y, Petrenko A, Geppert M, Sudhof T. Neurexins: synaptic cell surface proteins related to the alpha-latrotoxin receptor and laminin. Science. 1992;257:50-6 pubmed
    ..The polymorphic structure of the neurexins, their neural localization, and their sequence similarity to proteins associated with neurogenesis suggest a function as cell recognition molecules in the nerve terminal. ..
  4. Nguyen T, Sudhof T. Binding properties of neuroligin 1 and neurexin 1beta reveal function as heterophilic cell adhesion molecules. J Biol Chem. 1997;272:26032-9 pubmed
  5. Chubykin A, Liu X, Comoletti D, Tsigelny I, Taylor P, Sudhof T. Dissection of synapse induction by neuroligins: effect of a neuroligin mutation associated with autism. J Biol Chem. 2005;280:22365-74 pubmed
  6. Ullrich B, Ushkaryov Y, Sudhof T. Cartography of neurexins: more than 1000 isoforms generated by alternative splicing and expressed in distinct subsets of neurons. Neuron. 1995;14:497-507 pubmed
    ..Characterization of many independent bovine neurexin I alpha cDNAs suggests that different splice sites are used independently...
  7. 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. ..
  8. Ko J, Zhang C, Arac D, Boucard A, Brunger A, Sudhof T. Neuroligin-1 performs neurexin-dependent and neurexin-independent functions in synapse validation. EMBO J. 2009;28:3244-55 pubmed publisher
    ..Thus, neuroligin-1 performs diverse synaptic functions by mechanisms that include as essential components of alpha-neurexin binding and neuroligin dimerization, but extend beyond these activities. ..
  9. Fabrichny I, Leone P, Sulzenbacher G, Comoletti D, Miller M, Taylor P, et al. Structural analysis of the synaptic protein neuroligin and its beta-neurexin complex: determinants for folding and cell adhesion. Neuron. 2007;56:979-91 pubmed
    ..These structures exemplify how an alpha/beta-hydrolase fold varies in surface topography to confer adhesion properties and provide templates for analyzing abnormal processing or recognition events associated with autism. ..

More Information

Publications63

  1. Shapiro Reznik M, Jilg A, Lerner H, Earnest D, Zisapel N. Diurnal rhythms in neurexins transcripts and inhibitory/excitatory synapse scaffold proteins in the biological clock. PLoS ONE. 2012;7:e37894 pubmed publisher
    The neurexin genes (NRXN1/2/3) encode two families (? and ?) of highly polymorphic presynaptic proteins that are involved in excitatory/inhibitory synaptic balance...
  2. Rudenko G, Nguyen T, Chelliah Y, Sudhof T, Deisenhofer J. The structure of the ligand-binding domain of neurexin Ibeta: regulation of LNS domain function by alternative splicing. Cell. 1999;99:93-101 pubmed
    ..These splice sites are localized within loops at one edge of the jelly roll, suggesting a distinct protein interaction surface in LNS domains that is regulated by alternative splicing. ..
  3. Sugita S, Saito F, Tang J, Satz J, Campbell K, Sudhof T. A stoichiometric complex of neurexins and dystroglycan in brain. J Cell Biol. 2001;154:435-45 pubmed
    ..Our data indicate that dystroglycan is a physiological ligand for neurexins and that neurexins' tightly regulated interaction could mediate cell adhesion between brain cells. ..
  4. 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
  5. 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. ..
  6. 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. ..
  7. Tanaka H, Miyazaki N, Matoba K, Nogi T, Iwasaki K, Takagi J. Higher-order architecture of cell adhesion mediated by polymorphic synaptic adhesion molecules neurexin and neuroligin. Cell Rep. 2012;2:101-10 pubmed publisher
  8. 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. ..
  9. Suckow A, Comoletti D, Waldrop M, Mosedale M, Egodage S, Taylor P, et al. Expression of neurexin, neuroligin, and their cytoplasmic binding partners in the pancreatic beta-cells and the involvement of neuroligin in insulin secretion. Endocrinology. 2008;149:6006-17 pubmed publisher
    ..Analogous to their role in synaptic neurotransmission, neurexin-neuroligin interactions may play a role in the formation of the submembrane insulin secretory apparatus...
  10. Koehnke J, Jin X, Trbovic N, Katsamba P, Brasch J, Ahlsen G, et al. Crystal structures of beta-neurexin 1 and beta-neurexin 2 ectodomains and dynamics of splice insertion sequence 4. Structure. 2008;16:410-21 pubmed publisher
    ..These results raise the possibility that beta-NRX insertion sequence 4 may function in roles independent of neuroligin binding. ..
  11. Arac D, Boucard A, Ozkan E, Strop P, Newell E, Sudhof T, et al. Structures of neuroligin-1 and the neuroligin-1/neurexin-1 beta complex reveal specific protein-protein and protein-Ca2+ interactions. Neuron. 2007;56:992-1003 pubmed
    ..Our results provide molecular insights for understanding the role of cell-adhesion proteins in synapse function. ..
  12. 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. ..
  13. Berninghausen O, Rahman M, Silva J, Davletov B, Hopkins C, Ushkaryov Y. Neurexin Ibeta and neuroligin are localized on opposite membranes in mature central synapses. J Neurochem. 2007;103:1855-63 pubmed
    ..We have also demonstrated that neurexin Ibeta is largely (96%) pre-synaptic. Thus, neurexin Ibeta and neuroligin normally form trans-synaptic complexes and can transduce bidirectional signals. ..
  14. Ichtchenko K, Nguyen T, Sudhof T. Structures, alternative splicing, and neurexin binding of multiple neuroligins. J Biol Chem. 1996;271:2676-82 pubmed
    ..Thus, neuroligins constitute a multigene family of brain-specific proteins with distinct isoforms that may have overlapping functions in mediating recognition processes between neurons. ..
  15. Missler M, Hammer R, Sudhof T. Neurexophilin binding to alpha-neurexins. A single LNS domain functions as an independently folding ligand-binding unit. J Biol Chem. 1998;273:34716-23 pubmed
    ..The results support the notion that neurexophilins represent a family of extracellular signaling molecules that interact with multiple receptors including all three alpha-neurexins. ..
  16. Graf E, Kang Y, Hauner A, Craig A. Structure function and splice site analysis of the synaptogenic activity of the neurexin-1 beta LNS domain. J Neurosci. 2006;26:4256-65 pubmed
    ..These results suggest that differential neurexin-neuroligin binding affinities and splice variations may play an instructive role in postsynaptic differentiation. ..
  17. Leone P, Comoletti D, Ferracci G, Conrod S, Garcia S, Taylor P, et al. Structural insights into the exquisite selectivity of neurexin/neuroligin synaptic interactions. EMBO J. 2010;29:2461-71 pubmed publisher
    ..Although neuroligin-1 and neuroligin-2 have pre-determined conformations that respectively promote and prevent Nrx1beta association, unique conformational reshaping of the NL4 surface is required to permit Nrx1beta association. ..
  18. Ushkaryov Y, Hata Y, Ichtchenko K, Moomaw C, Afendis S, Slaughter C, et al. Conserved domain structure of beta-neurexins. Unusual cleaved signal sequences in receptor-like neuronal cell-surface proteins. J Biol Chem. 1994;269:11987-92 pubmed
    ..Thus, beta-neurexins are essentially N terminally truncated alpha-neurexins. ..
  19. 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
  20. 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. ..
  21. Sugita S, Khvochtev M, Sudhof T. Neurexins are functional alpha-latrotoxin receptors. Neuron. 1999;22:489-96 pubmed
    ..Thus, alpha-latrotoxin is unique among neurotoxins, because it utilizes two unrelated receptors, probably to amplify recruitment of alpha-latrotoxin to active sites. ..
  22. 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. ..
  23. Perin M. The COOH terminus of synaptotagmin mediates interaction with the neurexins. J Biol Chem. 1994;269:8576-81 pubmed
    ..I propose that the carboxyl terminus of synaptotagmin binds to the carboxyl terminus of the neurexins and that this interaction may mediate docking of synaptic vesicles or modulation of neurotransmitter release. ..
  24. Lu Z, Wang Y, Chen F, Tong H, Reddy M, Luo L, et al. Calsyntenin-3 molecular architecture and interaction with neurexin 1α. J Biol Chem. 2014;289:34530-42 pubmed publisher
    ..Cstn3 was recently shown in cell-based assays to interact with neurexin 1α (n1α), a synaptic organizer that is implicated in neuropsychiatric disease...
  25. Liu W, Wen W, Wei Z, Yu J, Ye F, Liu C, et al. The INAD scaffold is a dynamic, redox-regulated modulator of signaling in the Drosophila eye. Cell. 2011;145:1088-101 pubmed publisher
    ..These results show that scaffolding proteins can actively modulate the intrinsic redox potentials of their disulfide bonds to exert regulatory roles in signaling. ..
  26. Zahir F, Baross A, Delaney A, Eydoux P, Fernandes N, Pugh T, et al. A patient with vertebral, cognitive and behavioural abnormalities and a de novo deletion of NRXN1alpha. J Med Genet. 2008;45:239-43 pubmed
    ..3. The patient's deletion is approximately 320 kb in size and includes only the part of the NRXN1 gene that codes for the neurexin1alpha promoter and initial coding exons...
  27. 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. ..
  28. Gjørlund M, Nielsen J, Pankratova S, Li S, Korshunova I, Bock E, et al. Neuroligin-1 induces neurite outgrowth through interaction with neurexin-1? and activation of fibroblast growth factor receptor-1. FASEB J. 2012;26:4174-86 pubmed publisher
    Neurexin-1 (NRXN1) and neuroligin-1 (NLGN1) are synaptic cell adhesion molecules that connect pre- and postsynaptic neurons at synapses and mediate signaling across the synapse, which modulates synaptic activity and determines the ..
  29. Reissner C, Stahn J, Breuer D, Klose M, Pohlentz G, Mormann M, et al. Dystroglycan binding to α-neurexin competes with neurexophilin-1 and neuroligin in the brain. J Biol Chem. 2014;289:27585-603 pubmed publisher
    ..Using site-directed mutagenesis, we demonstrate the exact binding epitopes of αDAG and Nxph1 on Nrxn1α and show that their binding is mutually exclusive...
  30. Serova O, Radionov N, Shayahmetova D, Deyev I, Petrenko A. Structural and functional analyses of the sixth site of neurexin alternative splicing. Dokl Biochem Biophys. 2015;463:239-42 pubmed publisher
    ..The insertion in the SS6 site corresponds to the 9-residue peptide VALMKADLQ, which is conserved among animals. We demonstrated that the SS6 insertion regulates tissue-specific expression of neurexin 1α.
  31. Xiang Y, Dong H, Yang B, MacDonald J, Lu W. Interaction of acetylcholinesterase with neurexin-1? regulates glutamatergic synaptic stability in hippocampal neurons. Mol Brain. 2014;7:15 pubmed publisher
    ..This might serve a molecular mechanism of excessive AChE induced neurodegeneration. ..
  32. Mukherjee K, Sharma M, Urlaub H, Bourenkov G, Jahn R, Sudhof T, et al. CASK Functions as a Mg2+-independent neurexin kinase. Cell. 2008;133:328-39 pubmed publisher
    ..Moreover, our study suggests that other pseudokinases (10% of the kinome) could also be catalytically active. ..
  33. 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...
  34. Hock B, Böhme B, Karn T, Yamamoto T, Kaibuchi K, Holtrich U, et al. PDZ-domain-mediated interaction of the Eph-related receptor tyrosine kinase EphB3 and the ras-binding protein AF6 depends on the kinase activity of the receptor. Proc Natl Acad Sci U S A. 1998;95:9779-84 pubmed
  35. Feng J, Schroer R, Yan J, Song W, Yang C, Bockholt A, et al. High frequency of neurexin 1beta signal peptide structural variants in patients with autism. Neurosci Lett. 2006;409:10-3 pubmed
    ..In addition, no structural variant was found in the neurexin 2beta gene and the neurexin 3beta gene. In the context of all available data, we conclude that mutations of the neurexin 1beta gene may contribute to autism susceptibility. ..
  36. Raghavendra Rao V, Bowen K, Dhodda V, Song G, Franklin J, Gavva N, et al. Gene expression analysis of spontaneously hypertensive rat cerebral cortex following transient focal cerebral ischemia. J Neurochem. 2002;83:1072-86 pubmed
    ..galanin, neurotrimin, proteasome subunit RC8, synaptosomal-associated protein (SNAP)-25 A and B, synapsin 1a, neurexin 1-beta, ras-related rab3, vesicular GABA transporter (VGAT), digoxin carrier protein, neuronal calcium sensor-1 ..
  37. Shen K, Kuczynska D, Wu I, Murray B, Sheckler L, Rudenko G. Regulation of neurexin 1beta tertiary structure and ligand binding through alternative splicing. Structure. 2008;16:422-31 pubmed publisher
    ..Our structures reveal the mechanism by which neurexin 1beta isoforms acquire neuroligin splice isoform selectivity. ..
  38. Levinson J, Chery N, Huang K, Wong T, Gerrow K, Kang R, et al. Neuroligins mediate excitatory and inhibitory synapse formation: involvement of PSD-95 and neurexin-1beta in neuroligin-induced synaptic specificity. J Biol Chem. 2005;280:17312-9 pubmed
    ..Furthermore, relative levels of PSD-95 alter the ratio of excitatory to inhibitory synaptic contacts by sequestering members of the NLG family to excitatory synapses. ..
  39. Biederer T, Sudhof T. Mints as adaptors. Direct binding to neurexins and recruitment of munc18. J Biol Chem. 2000;275:39803-6 pubmed
    ..Our data support a model whereby one of the functions of Mints is to localize the vesicle fusion protein Munc18 to those sites at the plasma membrane that are defined by neurexins, presumably in the vicinity of points of exocytosis. ..
  40. 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. ..
  41. Esclassan F, Francois J, Phillips K, Loomis S, Gilmour G. Phenotypic characterization of nonsocial behavioral impairment in neurexin 1α knockout rats. Behav Neurosci. 2015;129:74-85 pubmed publisher
    ..Heterozygous partial deletions in the neurexin-1 gene (NRXN1, 2p16.3) have been observed in autism spectrum disorder (ASD) patients...
  42. Boucard A, Ko J, Sudhof T. High affinity neurexin binding to cell adhesion G-protein-coupled receptor CIRL1/latrophilin-1 produces an intercellular adhesion complex. J Biol Chem. 2012;287:9399-413 pubmed publisher
  43. Saito A, Miyauchi N, Hashimoto T, Karasawa T, Han G, Kayaba M, et al. Neurexin-1, a presynaptic adhesion molecule, localizes at the slit diaphragm of the glomerular podocytes in kidneys. Am J Physiol Regul Integr Comp Physiol. 2011;300:R340-8 pubmed publisher
    ..These observations suggest that neurexin is involved in the formation of the slit diaphragm and the maintenance of its function. ..
  44. Hata Y, Butz S, Sudhof T. CASK: a novel dlg/PSD95 homolog with an N-terminal calmodulin-dependent protein kinase domain identified by interaction with neurexins. J Neurosci. 1996;16:2488-94 pubmed
  45. Owczarek S, Bang M, Berezin V. Neurexin-Neuroligin Synaptic Complex Regulates Schizophrenia-Related DISC1/Kal-7/Rac1 "Signalosome". Neural Plast. 2015;2015:167308 pubmed publisher
    ..Our results indicate that the NX/NL synaptic complex is intrinsically involved in the regulation of DISC1 function, thus contributing to a better understanding of the pathology of schizophrenia. ..
  46. Futai K, Doty C, Baek B, Ryu J, Sheng M. Specific trans-synaptic interaction with inhibitory interneuronal neurexin underlies differential ability of neuroligins to induce functional inhibitory synapses. J Neurosci. 2013;33:3612-23 pubmed publisher
    ..Our results indicate that trans-synaptic interaction with differentially expressed presynaptic Nrxns underlies the distinct functions of NL1 and NL2, and is sufficient to induce functional inhibitory synapse formation. ..
  47. Comoletti D, De Jaco A, Jennings L, Flynn R, Gaietta G, Tsigelny I, et al. The Arg451Cys-neuroligin-3 mutation associated with autism reveals a defect in protein processing. J Neurosci. 2004;24:4889-93 pubmed
    ..Our findings reveal a cellular phenotype and loss of function for a congenital mutation associated with autistic spectrum disorders. ..
  48. Comoletti D, Flynn R, Boucard A, Demeler B, Schirf V, Shi J, et al. Gene selection, alternative splicing, and post-translational processing regulate neuroligin selectivity for beta-neurexins. Biochemistry. 2006;45:12816-27 pubmed
  49. 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 ..
  50. 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
  51. Wang Y, Dong J, Wang Y, Wei W, Song B, Shan Z, et al. Developmental Hypothyroxinemia and Hypothyroidism Reduce Parallel Fiber-Purkinje Cell Synapses in Rat Offspring by Downregulation of Neurexin1/Cbln1/GluD2 Tripartite Complex. Biol Trace Elem Res. 2016;173:465-74 pubmed publisher
    ..Our study supports the hypothesis that developmental hypothyroxinemia and hypothyroidism reduce PF-PC synapses, which may be attributed to the downregulation of Neurexin1/Cbln1/GluD2 tripartite complex. ..
  52. Cheng S, Seven A, Wang J, Skiniotis G, Ozkan E. Conformational Plasticity in the Transsynaptic Neurexin-Cerebellin-Glutamate Receptor Adhesion Complex. Structure. 2016;24:2163-2173 pubmed publisher
    ..Altogether, our results suggest unusual conformational flexibility within all components of the complex. ..
  53. Tabuchi K, Biederer T, Butz S, Sudhof T. CASK participates in alternative tripartite complexes in which Mint 1 competes for binding with caskin 1, a novel CASK-binding protein. J Neurosci. 2002;22:4264-73 pubmed
    ..experiments demonstrated that Caskin 1 coassembles with CASK on the immobilized cytoplasmic tail of neurexin 1, suggesting that CASK and Caskin 1 coat the cytoplasmic tails of neurexins and other cell-surface proteins...
  54. Sommer J, Schmitt A, Heck M, Schaeffer E, Fendt M, Zink M, et al. Differential expression of presynaptic genes in a rat model of postnatal hypoxia: relevance to schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2010;260 Suppl 2:S81-9 pubmed publisher
    ..Because of their primary presynaptic occurrence, five differentially expressed genes (CPX1, NPY, NRXN1, SNAP-25, and STX1A) have been selected for comparisons with clozapine-treated animals by qRT-PCR...