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Gene Review

RTN1  -  reticulon 1

Homo sapiens

Synonyms: NSP, Neuroendocrine-specific protein, Reticulon-1
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Disease relevance of RTN1

  • Reticulon proteins: emerging players in neurodegenerative diseases [1].
  • NSP-encoded reticulons are neuroendocrine markers of a novel category in human lung cancer diagnosis [2].
  • Maternal hypothyroidism selectively affects the expression of neuroendocrine-specific protein A messenger ribonucleic acid in the proliferative zone of the fetal rat brain cortex [3].
  • RS is less effective than NSP in stool bulking, but epidemiological data suggest that it is more protective against colorectal cancer, possibly via butyrate [4].
  • The rubella virus (RUB) nonstructural (NS) protein (NSP) ORF encodes a protease that cleaves the NSP precursor (240 kDa) at a single site to produce two products [5].

Psychiatry related information on RTN1


High impact information on RTN1


Chemical compound and disease context of RTN1


Biological context of RTN1

  • The presence of alternative promoters for gene expression and multiple cryptic splicing sites have resulted in large numbers of genes/proteins that are classified among the reticulon family [1].
  • In mammalian genomes, transcripts are produced from four genes, rtn1 to rtn4, under the regulation of tissue or cell-type-specific expression [1].
  • The last 6 exons, which are present in both transcripts, share significant amino acid sequence identity with the endoplasmic reticulum-bound portion of NSP [12].
  • Reticulon 4-A is under intense investigation because of its inhibitory effect on neurite outgrowth, and reticulon 4-B has been suggested to induce apoptosis [13].
  • Transient expression assays with a set of human PC1 gene fragments containing progressive 5' deletions demonstrate that the proximal promoter region is capable of directing high levels of neuroendocrine-specific expression of reporter gene constructs [14].

Anatomical context of RTN1


Associations of RTN1 with chemical compounds

  • The data implicate a novel ER localization mechanism for this neuroendocrine-specific luminal ER resident [18].
  • The ASYIP protein contains two hydrophobic regions and a double lysine endoplasmic reticulum (ER) retrieval motif at its C-terminus, which was shown to be identical to RTN3, a reticulon family protein of unknown function [19].
  • Identification of neuroendocrine-specific protein as an ethanol-regulated gene with mRNA differential display [20].
  • MIS inhibited the proliferation of both SP and NSP cells, whereas the lipophilic chemotherapeutic agent doxorubicin more significantly inhibited the NSP cells [21].
  • Rab3A is a neural/neuroendocrine-specific member of the Rab family involved in Ca(2+) -regulated exocytosis, where it functions in an inhibitory capacity controlling recruitment of secretory vesicles into a releasable pool at the plasma membrane [22].

Physical interactions of RTN1


Other interactions of RTN1

  • Like the RTN1 gene, the RTN2 gene is transcribed into different mRNA variants [15].
  • By using the yeast two-hybrid system, we have identified a member of the reticulon (RTN) family (RTN-1C) as the major GCS-protein partner [24].
  • It is interesting to note that RTN1 is localized to 14q23.1 where SPG15 locus was mapped [23].
  • The hypothesis that Nogo-A (Reticulon 4A) and Nogo-66 receptor (NgR1) limit adult CNS axonal growth after injury is supported by both in vitro experiments and in vivo pharmacological studies [25].
  • Spastin mediates its interaction with RTN1 through its N-terminal region containing a microtubule-interacting and trafficking domain [23].

Analytical, diagnostic and therapeutic context of RTN1

  • Neuroendocrine-specific protein (NSP) reticulons are expressed in neural and neuroendocrine tissues and cell cultures derived therefrom, while most other cell types lack NSP-reticulons [26].
  • Western blot analysis confirmed the presence of NSP-reticulon expression in these non-SCLC-NE cell lines, and showed that they were predominantly of the NSP-A type [27].
  • Regional mapping of the human NSP gene to chromosome region 14q21-->q22 by fluorescence in situ hybridization analysis [28].
  • The calculated energy excretion from the stoma was three times higher after flaked than after milled barley [51.5 decreasing to 15.3 kJ/g nonstarch polysaccharide (NSP, P < 0.001] [29].
  • Sequence analysis has revealed structures within the 3'-UTR that are conserved in these mRNAs and human NSP mRNA and that could be involved in specific compartmentalization of s-rex/NSP mRNA in neuronal cells [30].


  1. Reticulon proteins: emerging players in neurodegenerative diseases. Yan, R., Shi, Q., Hu, X., Zhou, X. Cell. Mol. Life Sci. (2006) [Pubmed]
  2. NSP-encoded reticulons are neuroendocrine markers of a novel category in human lung cancer diagnosis. van de Velde, H.J., Senden, N.H., Roskams, T.A., Broers, J.L., Ramaekers, F.C., Roebroek, A.J., Van de Ven, W.J. Cancer Res. (1994) [Pubmed]
  3. Maternal hypothyroidism selectively affects the expression of neuroendocrine-specific protein A messenger ribonucleic acid in the proliferative zone of the fetal rat brain cortex. Dowling, A.L., Iannacone, E.A., Zoeller, R.T. Endocrinology (2001) [Pubmed]
  4. Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Topping, D.L., Clifton, P.M. Physiol. Rev. (2001) [Pubmed]
  5. Characterization of the zinc binding activity of the rubella virus nonstructural protease. Liu, X., Yang, J., Ghazi, A.M., Frey, T.K. J. Virol. (2000) [Pubmed]
  6. Neural stem cell proliferation is decreased in schizophrenia, but not in depression. Reif, A., Fritzen, S., Finger, M., Strobel, A., Lauer, M., Schmitt, A., Lesch, K.P. Mol. Psychiatry (2006) [Pubmed]
  7. Neuroendocrine-specific protein C, a marker of neuronal differentiation, is reduced in brain of patients with Down syndrome and Alzheimer's disease. Kim, S.H., Yoo, B.C., Broers, J.L., Cairns, N., Lubec, G. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  8. Diet and haemostasis: time for nutrition science to get more involved. Vorster, H.H., Cummings, J.H., Veldman, F.J. Br. J. Nutr. (1997) [Pubmed]
  9. Reticulon family members modulate BACE1 activity and amyloid-beta peptide generation. He, W., Lu, Y., Qahwash, I., Hu, X.Y., Chang, A., Yan, R. Nat. Med. (2004) [Pubmed]
  10. Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein. GrandPré, T., Nakamura, F., Vartanian, T., Strittmatter, S.M. Nature (2000) [Pubmed]
  11. Neuron specific protein (NSP) in neuroblastoma cells: relation to differentiation. Marangos, P.J., Goodwin, F.K., Parma, A., Lauter, C., Trams, E. Brain Res. (1978) [Pubmed]
  12. Molecular cloning of a novel mouse gene with predominant muscle and neural expression. Geisler, J.G., Stubbs, L.J., Wasserman, W.W., Mucenski, M.L. Mamm. Genome (1998) [Pubmed]
  13. Reticulon 4 in chondrocytic cells: barosensitivity and intracellular localization. Sironen, R.K., Karjalainen, H.M., Törrönen, K.J., Elo, M.A., Hyttinen, M.M., Helminen, H.J., Lammi, M.J. Int. J. Biochem. Cell Biol. (2004) [Pubmed]
  14. Neuroendocrine-specific expression of the human prohormone convertase 1 gene. Hormonal regulation of transcription through distinct cAMP response elements. Jansen, E., Ayoubi, T.A., Meulemans, S.M., Van de Ven, W.J. J. Biol. Chem. (1995) [Pubmed]
  15. cDNA cloning, genomic organization, and expression of the human RTN2 gene, a member of a gene family encoding reticulons. Roebroek, A.J., Contreras, B., Pauli, I.G., Van de Ven, W.J. Genomics (1998) [Pubmed]
  16. Analysis of the reticulon gene family demonstrates the absence of the neurite growth inhibitor Nogo-A in fish. Diekmann, H., Klinger, M., Oertle, T., Heinz, D., Pogoda, H.M., Schwab, M.E., Stuermer, C.A. Mol. Biol. Evol. (2005) [Pubmed]
  17. NSP-encoded reticulons, neuroendocrine proteins of a novel gene family associated with membranes of the endoplasmic reticulum. van de Velde, H.J., Roebroek, A.J., Senden, N.H., Ramaekers, F.C., Van de Ven, W.J. J. Cell. Sci. (1994) [Pubmed]
  18. A neuroendocrine-specific protein localized to the endoplasmic reticulum by distal degradation. Schiller, M.R., Mains, R.E., Eipper, B.A. J. Biol. Chem. (1995) [Pubmed]
  19. Pro-apoptotic ASY/Nogo-B protein associates with ASYIP. Qi, B., Qi, Y., Watari, A., Yoshioka, N., Inoue, H., Minemoto, Y., Yamashita, K., Sasagawa, T., Yutsudo, M. J. Cell. Physiol. (2003) [Pubmed]
  20. Identification of neuroendocrine-specific protein as an ethanol-regulated gene with mRNA differential display. Schafer, G.L., Crabbe, J.C., Wiren, K.M. Mamm. Genome (1998) [Pubmed]
  21. Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian Inhibiting Substance responsiveness. Szotek, P.P., Pieretti-Vanmarcke, R., Masiakos, P.T., Dinulescu, D.M., Connolly, D., Foster, R., Dombkowski, D., Preffer, F., Maclaughlin, D.T., Donahoe, P.K. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  22. A direct inhibitory role for the Rab3-specific effector, Noc2, in Ca2+-regulated exocytosis in neuroendocrine cells. Haynes, L.P., Evans, G.J., Morgan, A., Burgoyne, R.D. J. Biol. Chem. (2001) [Pubmed]
  23. Spastin, the most commonly mutated protein in hereditary spastic paraplegia interacts with Reticulon 1 an endoplasmic reticulum protein. Mannan, A.U., Boehm, J., Sauter, S.M., Rauber, A., Byrne, P.C., Neesen, J., Engel, W. Neurogenetics (2006) [Pubmed]
  24. Glucosylceramide synthase and its functional interaction with RTN-1C regulate chemotherapeutic-induced apoptosis in neuroepithelioma cells. Di Sano, F., Fazi, B., Citro, G., Lovat, P.E., Cesareni, G., Piacentini, M. Cancer Res. (2003) [Pubmed]
  25. The nogo-nogo receptor pathway limits a spectrum of adult CNS axonal growth. Cafferty, W.B., Strittmatter, S.M. J. Neurosci. (2006) [Pubmed]
  26. Neuronal differentiation is accompanied by NSP-C expression. Hens, J., Nuydens, R., Geerts, H., Senden, N.H., Van de Ven, W.J., Roebroek, A.J., van de Velde, H.J., Ramaekers, F.C., Broers, J.L. Cell Tissue Res. (1998) [Pubmed]
  27. Neuroendocrine-specific protein (NSP)-reticulons as independent markers for non-small cell lung cancer with neuroendocrine differentiation. An in vitro histochemical study. Senden, N., Linnoila, I., Timmer, E., van de Velde, H., Roebroek, A., Van de Ven, W., Broers, J., Ramaekers, F. Histochem. Cell Biol. (1997) [Pubmed]
  28. Regional mapping of the human NSP gene to chromosome region 14q21-->q22 by fluorescence in situ hybridization analysis. Kools, P.F., Roebroek, A.J., Van de Velde, H.J., Marynen, P., Bullerdiek, J., Van de Ven, W.J. Cytogenet. Cell Genet. (1994) [Pubmed]
  29. Influence of the physical form of barley grain on the digestion of its starch in the human small intestine and implications for health. Livesey, G., Wilkinson, J.A., Roe, M., Faulks, R., Clark, S., Brown, J.C., Kennedy, H., Elia, M. Am. J. Clin. Nutr. (1995) [Pubmed]
  30. Rat and chicken s-rex/NSP mRNA: nucleotide sequence of main transcripts and expression of splice variants in rat tissues. Ninkina, N.N., Baka, I.D., Buchman, V.L. Gene (1997) [Pubmed]
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