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NTN1  -  netrin 1

Homo sapiens

Synonyms: Epididymis tissue protein Li 131P, NTN1L, Netrin-1
 
 
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Disease relevance of NTN1

 

Psychiatry related information on NTN1

 

High impact information on NTN1

  • Deleted in Colorectal Cancer (DCC) encodes a netrin receptor [6].
  • The importance of this interactive signaling is illustrated by the action of glial transcription factors and of glial axon guidance cues such as netrin and slit, which together regulate the commissural crossing of pioneer axons at the neural midline [7].
  • Netrin-1-mediated axon outgrowth and cAMP production requires interaction with adenosine A2b receptor [8].
  • Finally, we show that netrin-1-dependent outgrowth of dorsal spinal cord axons directly involves A2b [8].
  • Named after the Sanskrit word netr, which means 'one who guides', the netrin family of secreted proteins provides migrational cues in the developing central nervous system [9].
 

Biological context of NTN1

 

Anatomical context of NTN1

  • In normal adult pancreas there was very little netrin-1 expression [11].
  • We could show that netrin-1 increases the migration of fetal islet cells and of a ductal cell line, mainly via a chemokinetic effect [11].
  • Netrin-1 expression in fetal and regenerating rat pancreas and its effect on the migration of human pancreatic duct and porcine islet precursor cells [11].
  • In the developing nervous system, netrin protein secreted by midline cells attracts commissural axons by activating the DCC receptor on growth cones [12].
  • Using a collagen gel culture system, we examined effects of secreted molecules Netrin-1 and Slits on neurite outgrowth of fetal DA neurons and murine ES-differentiated DA neurons [13].
 

Associations of NTN1 with chemical compounds

 

Physical interactions of NTN1

  • Together our results indicate that the growth-promoting function of netrin-1 may require a receptor complex containing DCC and A2b [8].
  • We now identify Grb7 as a new RNA-binding protein that serves as the molecular adaptor for transmitting Netrin-1 signals, through focal adhesion kinase (FAK), to the translation machinery [19].
 

Enzymatic interactions of NTN1

 

Regulatory relationships of NTN1

 

Other interactions of NTN1

 

Analytical, diagnostic and therapeutic context of NTN1

References

  1. Netrin induces down-regulation of its receptor, Deleted in Colorectal Cancer, through the ubiquitin-proteasome pathway in the embryonic cortical neuron. Kim, T.H., Lee, H.K., Seo, I.A., Bae, H.R., Suh, D.J., Wu, J., Rao, Y., Hwang, K.G., Park, H.T. J. Neurochem. (2005) [Pubmed]
  2. Netrin-1: interaction with deleted in colorectal cancer (DCC) and alterations in brain tumors and neuroblastomas. Meyerhardt, J.A., Caca, K., Eckstrand, B.C., Hu, G., Lengauer, C., Banavali, S., Look, A.T., Fearon, E.R. Cell Growth Differ. (1999) [Pubmed]
  3. Netrin-1 inhibits leukocyte migration in vitro and in vivo. Ly, N.P., Komatsuzaki, K., Fraser, I.P., Tseng, A.A., Prodhan, P., Moore, K.J., Kinane, T.B. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  4. Enhanced expression of netrin-1 protein in the sciatic nerves of Lewis rats with experimental autoimmune neuritis: possible role of the netrin-1/DCC binding pathway in an autoimmune PNS disorder. Moon, C., Kim, H., Ahn, M., Jin, J.K., Wang, H., Matsumoto, Y., Shin, T. J. Neuroimmunol. (2006) [Pubmed]
  5. The role of the floor plate in axon guidance. Colamarino, S.A., Tessier-Lavigne, M. Annu. Rev. Neurosci. (1995) [Pubmed]
  6. Deleted in Colorectal Cancer (DCC) encodes a netrin receptor. Keino-Masu, K., Masu, M., Hinck, L., Leonardo, E.D., Chan, S.S., Culotti, J.G., Tessier-Lavigne, M. Cell (1996) [Pubmed]
  7. Glial control of neuronal development. Lemke, G. Annu. Rev. Neurosci. (2001) [Pubmed]
  8. Netrin-1-mediated axon outgrowth and cAMP production requires interaction with adenosine A2b receptor. Corset, V., Nguyen-Ba-Charvet, K.T., Forcet, C., Moyse, E., Chédotal, A., Mehlen, P. Nature (2000) [Pubmed]
  9. Netrins: beyond the brain. Cirulli, V., Yebra, M. Nat. Rev. Mol. Cell Biol. (2007) [Pubmed]
  10. UNC5A promotes neuronal apoptosis during spinal cord development independent of netrin-1. Williams, M.E., Lu, X., McKenna, W.L., Washington, R., Boyette, A., Strickland, P., Dillon, A., Kaprielian, Z., Tessier-Lavigne, M., Hinck, L. Nat. Neurosci. (2006) [Pubmed]
  11. Netrin-1 expression in fetal and regenerating rat pancreas and its effect on the migration of human pancreatic duct and porcine islet precursor cells. De Breuck, S., Lardon, J., Rooman, I., Bouwens, L. Diabetologia (2003) [Pubmed]
  12. Quantification of expression of netrins, slits and their receptors in human prostate tumors. Latil, A., Chêne, L., Cochant-Priollet, B., Mangin, P., Fournier, G., Berthon, P., Cussenot, O. Int. J. Cancer (2003) [Pubmed]
  13. Axonal growth regulation of fetal and embryonic stem cell-derived dopaminergic neurons by netrin-1 and slits. Lin, L., Isacson, O. Stem Cells (2006) [Pubmed]
  14. Mapping netrin receptor binding reveals domains of Unc5 regulating its tyrosine phosphorylation. Kruger, R.P., Lee, J., Li, W., Guan, K.L. J. Neurosci. (2004) [Pubmed]
  15. Turning of retinal growth cones in a netrin-1 gradient mediated by the netrin receptor DCC. de la Torre, J.R., Höpker, V.H., Ming, G.L., Poo, M.M., Tessier-Lavigne, M., Hemmati-Brivanlou, A., Holt, C.E. Neuron (1997) [Pubmed]
  16. Netrin binds discrete subdomains of DCC and UNC5 and mediates interactions between DCC and heparin. Geisbrecht, B.V., Dowd, K.A., Barfield, R.W., Longo, P.A., Leahy, D.J. J. Biol. Chem. (2003) [Pubmed]
  17. Netrin-1 and slit-2 regulate and direct neurite growth of ventral midbrain dopaminergic neurons. Lin, L., Rao, Y., Isacson, O. Mol. Cell. Neurosci. (2005) [Pubmed]
  18. Recognition of the neural chemoattractant Netrin-1 by integrins alpha6beta4 and alpha3beta1 regulates epithelial cell adhesion and migration. Yebra, M., Montgomery, A.M., Diaferia, G.R., Kaido, T., Silletti, S., Perez, B., Just, M.L., Hildbrand, S., Hurford, R., Florkiewicz, E., Tessier-Lavigne, M., Cirulli, V. Dev. Cell (2003) [Pubmed]
  19. The adaptor Grb7 links netrin-1 signaling to regulation of mRNA translation. Tsai, N.P., Bi, J., Wei, L.N. EMBO J. (2007) [Pubmed]
  20. DCC-dependent phospholipase C signaling in netrin-1-induced neurite elongation. Xie, Y., Hong, Y., Ma, X.Y., Ren, X.R., Ackerman, S., Mei, L., Xiong, W.C. J. Biol. Chem. (2006) [Pubmed]
  21. Rho inhibition recruits DCC to the neuronal plasma membrane and enhances axon chemoattraction to netrin 1. Moore, S.W., Correia, J.P., Lai Wing Sun, K., Pool, M., Fournier, A.E., Kennedy, T.E. Development (2008) [Pubmed]
  22. Characterization of the receptors for axon guidance factor netrin-4 and identification of the binding domains. Qin, S., Yu, L., Gao, Y., Zhou, R., Zhang, C. Mol. Cell. Neurosci. (2007) [Pubmed]
  23. The NTN2L gene encoding a novel human netrin maps to the autosomal dominant polycystic kidney disease region on chromosome 16p13.3. Van Raay, T.J., Foskett, S.M., Connors, T.D., Klinger, K.W., Landes, G.M., Burn, T.C. Genomics (1997) [Pubmed]
  24. FAK and Src kinases are required for netrin-induced tyrosine phosphorylation of UNC5. Li, W., Aurandt, J., Jürgense, C., Rao, Y., Guan, K.L. J. Cell. Sci. (2006) [Pubmed]
  25. Cellular expression of a leech netrin suggests roles in the formation of longitudinal nerve tracts and in regional innervation of peripheral targets. Gan, W.B., Wong, V.Y., Phillips, A., Ma, C., Gershon, T.R., Macagno, E.R. J. Neurobiol. (1999) [Pubmed]
 
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