This gene belongs to the family of reticulon-encoding genes. Reticulons are associated with the endoplasmic reticulum, and are involved in neuroendocrine secretion or in membrane trafficking in neuroendocrine cells. The product of this gene is a potent neurite outgrowth inhibitor that may also help block the regeneration of the central nervous system in higher vertebrates. Alternatively spliced transcript variants derived both from differential splicing and differential promoter usage and encoding different isoforms have been identified. There are three isoforms: Nogo A, B and C. Nogo-A has two known inhibitory domains including amino-Nogo, at the N-terminus and Nogo-66, which makes up the molecules extracellular loop. Both amino-Nogo and Nogo-66 are involved in inhibitory responses, where amino-Nogo is a strong inhibitor of neurite outgrowth, and Nogo-66 is involved in growth cone destruction.
Research suggests that blocking Nogo-A during neuronal damage (from diseases such as Multiple Sclerosis) will help to protect or restore the damaged neurons. The investigation into the mechanisms of this protein presents a great potential for the treatment of auto-immune mediated demyelinating diseases and spinal cord injuryregeneration. It has also been found to be a key player in the process whereby physical exercise enhances learning and memory processes in the brain.
^GrandPre T, Nakamura F, Vartanian T, Strittmatter SM (February 2000). "Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein". Nature403 (6768): 439–44. doi:10.1038/35000226. PMID10667797.
^Yang J, Yu L, Bi AD, Zhao SY (June 2000). "Assignment of the human reticulon 4 gene (RTN4) to chromosome 2p14-->2p13 by radiation hybrid mapping". Cytogenet Cell Genet88 (1–2): 101–2. doi:10.1159/000015499. PMID10773680.
^Qin, Haina; Pu Helen X; Li Minfen; Ahmed Sohail; Song Jianxing (December 2008). "Identification and structural mechanism for a novel interaction between a ubiquitin ligase WWP1 and Nogo-A, a key inhibitor for central nervous system regeneration". Biochemistry (United States) 47 (51): 13647–58. doi:10.1021/bi8017976. PMID19035836.
^ abTagami, S; Eguchi Y; Kinoshita M; Takeda M; Tsujimoto Y (November 2000). "A novel protein, RTN-XS, interacts with both Bcl-XL and Bcl-2 on endoplasmic reticulum and reduces their anti-apoptotic activity". Oncogene (England) 19 (50): 5736–46. doi:10.1038/sj.onc.1203948. ISSN0950-9232. PMID11126360.
Teng FY, Tang BL (August 2008). "Cell autonomous function of Nogo and reticulons: The emerging story at the endoplasmic reticulum". J. Cell. Physiol.216 (2): 303–8. doi:10.1002/jcp.21434. PMID18330888.
Ng CE, Tang BL (2002). "Nogos and the Nogo-66 receptor: factors inhibiting CNS neuron regeneration.". J. Neurosci. Res.67 (5): 559–65. doi:10.1002/jnr.10134. PMID11891768.
Watari A, Yutsudo M (2003). "Multi-functional gene ASY/Nogo/RTN-X/RTN4: apoptosis, tumor suppression, and inhibition of neuronal regeneration.". Apoptosis8 (1): 5–9. doi:10.1023/A:1021639016300. PMID12510146.
Nagase T, Ishikawa K, Suyama M, et al. (1999). "Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.". DNA Res.5 (6): 355–64. doi:10.1093/dnares/5.6.355. PMID10048485.
Chen MS, Huber AB, van der Haar ME, et al. (2000). "Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1.". Nature403 (6768): 434–9. doi:10.1038/35000219. PMID10667796.
Tagami S, Eguchi Y, Kinoshita M, et al. (2001). "A novel protein, RTN-XS, interacts with both Bcl-XL and Bcl-2 on endoplasmic reticulum and reduces their anti-apoptotic activity.". Oncogene19 (50): 5736–46. doi:10.1038/sj.onc.1203948. PMID11126360.
Fournier AE, GrandPre T, Strittmatter SM (2001). "Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration.". Nature409 (6818): 341–6. doi:10.1038/35053072. PMID11201742.
Josephson A, Widenfalk J, Widmer HW, et al. (2001). "NOGO mRNA expression in adult and fetal human and rat nervous tissue and in weight drop injury.". Exp. Neurol.169 (2): 319–28. doi:10.1006/exnr.2001.7659. PMID11358445.
Liu BP, Fournier A, GrandPré T, Strittmatter SM (2002). "Myelin-associated glycoprotein as a functional ligand for the Nogo-66 receptor.". Science297 (5584): 1190–3. doi:10.1126/science.1073031. PMID12089450.
Dupuis L, Gonzalez de Aguilar JL, di Scala F, et al. (2002). "Nogo provides a molecular marker for diagnosis of amyotrophic lateral sclerosis.". Neurobiol. Dis.10 (3): 358–65. doi:10.1006/nbdi.2002.0522. PMID12270696.
Taketomi M, Kinoshita N, Kimura K, et al. (2002). "Nogo-A expression in mature oligodendrocytes of rat spinal cord in association with specific molecules.". Neurosci. Lett.332 (1): 37–40. doi:10.1016/S0304-3940(02)00910-2. PMID12377379.
Li M, Shi J, Wei Z, Teng FY, Tang BL, Song J. (2004). "Structural characterization of the human Nogo-A functional domains. Solution structure of Nogo-40, a Nogo-66 receptor antagonist enhancing injured spinal cord regeneration.". Eur J Biochem.271 (17): 3512–22. doi:10.1111/j.0014-2956.2004.04286.x. PMID15317586.
Li M, Song J. (2007). "The N- and C-termini of the human Nogo molecules are intrinsically unstructured: bioinformatics, CD, NMR characterization, and functional implications.". Proteins.68 (1): 100–8. doi:10.1002/prot.21385. PMID17397058.
Li M, Song J. (2007). "Nogo-B receptor possesses an intrinsically unstructured ectodomain and a partially folded cytoplasmic domain.". Biochem Biophys Res Commun.360 (1): 128–34. doi:10.1016/j.bbrc.2007.06.031. PMID17585875.