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Gene Review

Nrg  -  Neuroglian

Drosophila melanogaster

Synonyms: CG1634, CT4318, Dmel\CG1634, NFASC, NRG, ...
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High impact information on Nrg

  • Drosophila neuroglian is an integral membrane glycoprotein that is expressed on a variety of cell types in the Drosophila embryo, including expression on a large subset of glial and neuronal cell bodies in the central and peripheral nervous systems and on the fasciculating axons that extend along them [1].
  • Its homology to L1 and its embryonic localization suggest that neuroglian may play a role in neural and glial cell adhesion in the developing Drosophila embryo [1].
  • Alternative splicing of the nrg transcript involves alternative inclusion of a 3'-terminal exon [2].
  • Here, using a minigene reporter, we show that the nrg alternatively spliced intron (nASI) has all the determinants required to recreate proper neural-specific RNA processing seen with the endogenous nrg transcript, including regulation by ELAV [2].
  • The neuron-specific RNA-binding protein ELAV regulates neuroglian alternative splicing in neurons and binds directly to its pre-mRNA [2].

Biological context of Nrg

  • Moreover, neuroglian loss-of-function phenotype can be suppressed by the expression of gain-of-function conditions of heartless or DER [3].
  • Neuroglian-mediated cell adhesion induces assembly of the membrane skeleton at cell contact sites [4].
  • Thus, the neuron-glia interaction that is mediated by Nrg, together with Ank under some situations, contributes to axonal and dendritic morphogenesis [5].
  • Using sequence polymorphism at the Nrg locus, we showed that sex-ratio has induced a strong selective sweep in populations from Madagascar and Réunion, where distorting chromosomes are close to a 50% frequency [6].
  • Here we show that the neuroglian gene generates at least two different protein products by tissue-specific alternative splicing [7].

Anatomical context of Nrg


Associations of Nrg with chemical compounds

  • The results are consistent with a scenario where the activity of these receptor tyrosine kinases is controlled by Neuroglian at choice points where sensory axons select between alternative substrates for extension [3].
  • Each domain consists of two antiparallel beta sheets and is folded topologically identically to single fibronectin type III domains from the extracellular matrix proteins tenascin and fibronectin. beta bulges and left-handed polyproline II helices disrupt the regular beta sheet structure of both neuroglian domains [10].
  • The ibx strain has a missense mutation causing a glycine-to-arginine change at amino acid 92 in the first immunoglobulin domain of nrg [11].
  • Here we examined the effect of physiologically relevant concentrations of ethanol on the aggregation of Drosophila S2 cells that expressed either neuroglian (the Drosophila homolog of L1) or human L1 [12].

Physical interactions of Nrg

  • We localized the region of neuroglian that interacts with ankyrin and investigated the mechanism that limits this interaction to cell contact sites [13].

Regulatory relationships of Nrg


Other interactions of Nrg

  • Together, our results suggest a model in which Nrg acts as a heterophilic ligand and activator of Ed, which in turn antagonizes EGFR signaling [14].
  • We show that CONT, Neuroglian (NRG) (Drosophila homolog of NF-155) and NRX IV are interdependent for their SJ localization and these proteins form a tripartite complex [16].
  • Upon expression of an inducible neuroglian minigene, however, cells aggregated into large clusters and ankyrin became concentrated at sites of cell-cell contact [4].
  • Neuroglian and DE-cadherin activate independent cytoskeleton assembly pathways in Drosophila S2 cells [17].
  • A third artificial neuroglian protein form was constructed by substituting the neuroglian transmembrane segment and cytoplasmic domains with the glycosyl phosphatidylinositol attachment signal of the Drosophila fasciclin I protein [18].

Analytical, diagnostic and therapeutic context of Nrg


  1. Drosophila neuroglian: a member of the immunoglobulin superfamily with extensive homology to the vertebrate neural adhesion molecule L1. Bieber, A.J., Snow, P.M., Hortsch, M., Patel, N.H., Jacobs, J.R., Traquina, Z.R., Schilling, J., Goodman, C.S. Cell (1989) [Pubmed]
  2. The neuron-specific RNA-binding protein ELAV regulates neuroglian alternative splicing in neurons and binds directly to its pre-mRNA. Lisbin, M.J., Qiu, J., White, K. Genes Dev. (2001) [Pubmed]
  3. The EGF and FGF receptors mediate neuroglian function to control growth cone decisions during sensory axon guidance in Drosophila. García-Alonso, L., Romani, S., Jiménez, F. Neuron (2000) [Pubmed]
  4. Neuroglian-mediated cell adhesion induces assembly of the membrane skeleton at cell contact sites. Dubreuil, R.R., MacVicar, G., Dissanayake, S., Liu, C., Homer, D., Hortsch, M. J. Cell Biol. (1996) [Pubmed]
  5. Control of axonal sprouting and dendrite branching by the Nrg-Ank complex at the neuron-glia interface. Yamamoto, M., Ueda, R., Takahashi, K., Saigo, K., Uemura, T. Curr. Biol. (2006) [Pubmed]
  6. Signature of selective sweep associated with the evolution of sex-ratio drive in Drosophila simulans. Derome, N., Métayer, K., Montchamp-Moreau, C., Veuille, M. Genetics (2004) [Pubmed]
  7. Differential splicing generates a nervous system-specific form of Drosophila neuroglian. Hortsch, M., Bieber, A.J., Patel, N.H., Goodman, C.S. Neuron (1990) [Pubmed]
  8. Axonal ensheathment and septate junction formation in the peripheral nervous system of Drosophila. Banerjee, S., Pillai, A.M., Paik, R., Li, J., Bhat, M.A. J. Neurosci. (2006) [Pubmed]
  9. A conserved role for Drosophila Neuroglian and human L1-CAM in central-synapse formation. Godenschwege, T.A., Kristiansen, L.V., Uthaman, S.B., Hortsch, M., Murphey, R.K. Curr. Biol. (2006) [Pubmed]
  10. Crystal structure of tandem type III fibronectin domains from Drosophila neuroglian at 2.0 A. Huber, A.H., Wang, Y.M., Bieber, A.J., Bjorkman, P.J. Neuron (1994) [Pubmed]
  11. Female receptivity phenotype of icebox mutants caused by a mutation in the L1-type cell adhesion molecule neuroglian. Carhan, A., Allen, F., Armstrong, J.D., Goodwin, S.F., O'Dell, K.M. Genes Brain Behav. (2005) [Pubmed]
  12. Ethanol does not inhibit the adhesive activity of Drosophila neuroglian or human L1 in Drosophila S2 tissue culture cells. Vallejo, Y., Hortsch, M., Dubreuil, R.R. J. Biol. Chem. (1997) [Pubmed]
  13. Structural requirements for outside-in and inside-out signaling by Drosophila neuroglian, a member of the L1 family of cell adhesion molecules. Hortsch, M., Homer, D., Malhotra, J.D., Chang, S., Frankel, J., Jefford, G., Dubreuil, R.R. J. Cell Biol. (1998) [Pubmed]
  14. Neuroglian activates Echinoid to antagonize the Drosophila EGF receptor signaling pathway. Islam, R., Wei, S.Y., Chiu, W.H., Hortsch, M., Hsu, J.C. Development (2003) [Pubmed]
  15. Segregation of two spectrin isoforms: polarized membrane-binding sites direct polarized membrane skeleton assembly. Dubreuil, R.R., Maddux, P.B., Grushko, T.A., MacVicar, G.R. Mol. Biol. Cell (1997) [Pubmed]
  16. Drosophila contactin, a homolog of vertebrate contactin, is required for septate junction organization and paracellular barrier function. Faivre-Sarrailh, C., Banerjee, S., Li, J., Hortsch, M., Laval, M., Bhat, M.A. Development (2004) [Pubmed]
  17. Neuroglian and DE-cadherin activate independent cytoskeleton assembly pathways in Drosophila S2 cells. Dubreuil, R.R., Grushko, T. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  18. The cytoplasmic domain of the Drosophila cell adhesion molecule neuroglian is not essential for its homophilic adhesive properties in S2 cells. Hortsch, M., Wang, Y.M., Marikar, Y., Bieber, A.J. J. Biol. Chem. (1995) [Pubmed]
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