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Gene Review

Nrt  -  Neurotactin

Drosophila melanogaster

Synonyms: BP106, BcDNA:LD22004, CG9704, DAB, Dab, ...
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Disease relevance of Nrt

  • Analysis of both loss and gain of gene function conditions during embryonic and postembryonic development revealed specific requirements for neurotactin during axon outgrowth, fasciculation, and guidance [1].
  • Now, in this issue of the Biochemical Journal, Takenawa and colleagues have demonstrated that Disabled also acts in a pathway to regulate actin dynamics through the direct activation of N-WASP (neuronal Wiskott-Aldrich syndrome protein) [2].
  • ESX is located at chromosome 1q32 in a region known to be amplified in 50% of early breast cancers, is heregulin-inducible and overexpressed in HER2/neu activated breast cancer cells [3].

High impact information on Nrt

  • We have isolated and characterized mutations in Drosophila neurotactin, a gene that encodes a cell adhesion protein widely expressed during neural development [1].
  • Neurotactin functions in concert with other identified CAMs in growth cone guidance in Drosophila [1].
  • Furthermore, AMA is necessary for NRT-expressing cells both to aggregate with themselves and to associate with embryonic primary culture cells [4].
  • Pupae deficient for ama do exhibit defasciculation defects of the ocellar nerves similar to those found in nrt mutants [4].
  • Here, we identify a mouse homolog of the Drosophila Disabled (Dab) protein, mDab1, and show it is an adaptor molecule functioning in neural development [5].

Biological context of Nrt

  • Cell culture experiments demonstrate the Ama(M109) mutant protein binds to Nrt, but is defective in mediating Ama/Nrt cell adhesion [6].
  • Heterozygous null alleles of nrt dominantly enhance the Abl mutant phenotype, also affecting axon pathfinding [6].
  • By using truncated Nrt molecules and a homotypic cell aggregation assay which involves a soluble ligand activity, it has been possible to show that the adhesive function is localized in the N-terminal region of the extracellular domain comprised between His347 and His482 [7].
  • Neurotactin is regionally expressed at the cellular blastoderm stage; later in embryogenesis the expression of the protein becomes restricted to cells of the peripheral and central nervous system [8].
  • The extracellular domain at the carboxyterminal end of the neurotactin protein shows a strong structural and sequence homology to serine esterases without retaining the amino acids forming the active center [8].

Anatomical context of Nrt


Associations of Nrt with chemical compounds

  • Interactions between the secreted protein Amalgam, its transmembrane receptor Neurotactin and the Abelson tyrosine kinase affect axon pathfinding [6].
  • Neurotactin (Nrt), a Drosophila transmembrane glycoprotein which is expressed in neuronal and epithelial tissues during embryonic and larval stages, exhibits heterophilic adhesive properties [7].
  • It has been observed that in female CBA, SHR, SAM and transgenic HER-2/neu mice long-term administration of melatonin was followed by an increase in the mean life span [12].

Other interactions of Nrt


Analytical, diagnostic and therapeutic context of Nrt


  1. Neurotactin functions in concert with other identified CAMs in growth cone guidance in Drosophila. Speicher, S., García-Alonso, L., Carmena, A., Martín-Bermudo, M.D., de la Escalera, S., Jiménez, F. Neuron (1998) [Pubmed]
  2. Filopodia formation and Disabled degradation downstream of Reelin. Winder, S.J. Biochem. J. (2004) [Pubmed]
  3. ESX: a structurally unique Ets overexpressed early during human breast tumorigenesis. Chang, C.H., Scott, G.K., Kuo, W.L., Xiong, X., Suzdaltseva, Y., Park, J.W., Sayre, P., Erny, K., Collins, C., Gray, J.W., Benz, C.C. Oncogene (1997) [Pubmed]
  4. Amalgam is a ligand for the transmembrane receptor neurotactin and is required for neurotactin-mediated cell adhesion and axon fasciculation in Drosophila. Frémion, F., Darboux, I., Diano, M., Hipeau-Jacquotte, R., Seeger, M.A., Piovant, M. EMBO J. (2000) [Pubmed]
  5. Mouse disabled (mDab1): a Src binding protein implicated in neuronal development. Howell, B.W., Gertler, F.B., Cooper, J.A. EMBO J. (1997) [Pubmed]
  6. Interactions between the secreted protein Amalgam, its transmembrane receptor Neurotactin and the Abelson tyrosine kinase affect axon pathfinding. Liebl, E.C., Rowe, R.G., Forsthoefel, D.J., Stammler, A.L., Schmidt, E.R., Turski, M., Seeger, M.A. Development (2003) [Pubmed]
  7. The structure-function relationships in Drosophila neurotactin show that cholinesterasic domains may have adhesive properties. Darboux, I., Barthalay, Y., Piovant, M., Hipeau-Jacquotte, R. EMBO J. (1996) [Pubmed]
  8. Drosophila neurotactin, a surface glycoprotein with homology to serine esterases, is dynamically expressed during embryogenesis. Hortsch, M., Patel, N.H., Bieber, A.J., Traquina, Z.R., Goodman, C.S. Development (1990) [Pubmed]
  9. Drosophila neurotactin mediates heterophilic cell adhesion. Barthalay, Y., Hipeau-Jacquotte, R., de la Escalera, S., Jiménez, F., Piovant, M. EMBO J. (1990) [Pubmed]
  10. Developmental architecture of adult-specific lineages in the ventral CNS of Drosophila. Truman, J.W., Schuppe, H., Shepherd, D., Williams, D.W. Development (2004) [Pubmed]
  11. Trafficking through Rab11 endosomes is required for cellularization during Drosophila embryogenesis. Pelissier, A., Chauvin, J.P., Lecuit, T. Curr. Biol. (2003) [Pubmed]
  12. Melatonin as antioxidant, geroprotector and anticarcinogen. Anisimov, V.N., Popovich, I.G., Zabezhinski, M.A., Anisimov, S.V., Vesnushkin, G.M., Vinogradova, I.A. Biochim. Biophys. Acta (2006) [Pubmed]
  13. A Drosophila receptor tyrosine phosphatase expressed in the embryonic CNS and larval optic lobes is a member of the set of proteins bearing the "HRP" carbohydrate epitope. Desai, C.J., Popova, E., Zinn, K. J. Neurosci. (1994) [Pubmed]
  14. Characterization and gene cloning of neurotactin, a Drosophila transmembrane protein related to cholinesterases. de la Escalera, S., Bockamp, E.O., Moya, F., Piovant, M., Jiménez, F. EMBO J. (1990) [Pubmed]
  15. The distribution of transcripts of neurogenic genes in neurogenic mutants of Drosophila melanogaster. Godt, D., Schrons, H., Guth, S., Campos-Ortega, J.A. J. Neurogenet. (1991) [Pubmed]
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