Reticulon 4

Reticulon 4
PDB rendering based on 2g31.
Available structures PDB 2G31, 2JV5
Identifiers
Symbols	RTN4; ASY; NI220/250; NOGO; NOGO-A; NOGOC; NSP; NSP-CL; Nbla00271; Nbla10545; Nogo-B; Nogo-C; RTN-X; RTN4-A; RTN4-B1; RTN4-B2; RTN4-C
External IDs	OMIM: 604475 MGI: 1915835 HomoloGene: 10743 GeneCards: RTN4 Gene
Gene Ontology Molecular function • protein binding • protein complex binding Cellular component • nuclear envelope • cytoplasm • endoplasmic reticulum • endoplasmic reticulum membrane • plasma membrane • integral to membrane • integral to endoplasmic reticulum membrane • neuron projection • neuronal cell body • myelin sheath • protein complex Biological process • angiogenesis • apoptosis • axonal fasciculation • aging • response to activity • negative regulation of anti-apoptosis • olfactory nerve development • cerebral cortex radial glia guided migration • negative regulation of cell growth • regulation of cell migration • negative regulation of axon extension • positive regulation of dopamine secretion • regulation of apoptosis • negative regulation of neuron differentiation • positive regulation of glial cell differentiation • nerve growth factor receptor signaling pathway • regulation of axon regeneration • oligodendrocyte differentiation • regulation of axonogenesis • negative regulation of axonogenesis • regulation of sensory perception of pain • cardiac epithelial to mesenchymal transition • negative regulation of neuron projection regeneration • endoplasmic reticulum tubular network organization • regulation of branching morphogenesis of a nerve Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	57142	68585
Ensembl	ENSG00000115310	ENSMUSG00000020458
UniProt	Q9NQC3	Q99P72
RefSeq (mRNA)	NM_007008.2	NM_024226
RefSeq (protein)	NP_008939.1	NP_077188
Location (UCSC)	Chr 2: 55.2 – 55.34 Mb	Chr 11: 29.59 – 29.64 Mb
PubMed search	[1]	[2]

Reticulon-4, also known as Neurite outgrowth inhibitor or Nogo, is a protein that in humans is encoded by the RTN4 gene^[1][2][3] that has been identified as an inhibitor of neurite outgrowth specific to the central nervous system.

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.^[3] 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.^[4]

Research suggests that blocking Nogo-A during neuronal damage (from diseases such as Multiple Sclerosis) will help to protect or restore the damaged neurons.^[4] The investigation into the mechanisms of this protein presents a great potential for the treatment of auto-immune mediated demyelinating diseases and spinal cord injury regeneration. It has also been found to be a key player in the process whereby physical exercise enhances learning and memory processes in the brain.^[5]

Interactions

Reticulon 4 has been shown to interact with WWP1,^[6] BCL2-like 1^[7] and Bcl-2.^[7]

See also

• Reticulon 4 receptor

References

1. ^ GrandPre T, Nakamura F, Vartanian T, Strittmatter SM (Feb 2000). "Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein". Nature 403 (6768): 439–44. doi:10.1038/35000226. PMID 10667797. 
2. ^ Yang J, Yu L, Bi AD, Zhao SY (Jun 2000). "Assignment of the human reticulon 4 gene (RTN4) to chromosome 2p14-->2p13 by radiation hybrid mapping". Cytogenet Cell Genet 88 (1-2): 101–2. doi:10.1159/000015499. PMID 10773680. 
3. ^ ^{a b} "Entrez Gene: RTN4 reticulon 4". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=57142. 
4. ^ ^{a b} Karnezis et al.; Mandemakers, W; McQualter, JL; Zheng, B; Ho, PP; Jordan, KA; Murray, BM; Barres, B et al. (2004). "The neurite outgrowth inhibitor Nogo A is involved in autoimmune-mediated demyelination.". Nature Neuroscience 7 (7): 736–744.. doi:10.1038/nn1261. PMID 15184901. 
5. ^ Stopping a receptor called 'nogo' boosts the synapses
6. ^ Qin, Haina; Pu Helen X, Li Minfen, Ahmed Sohail, Song Jianxing (Dec. 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. PMID 19035836. 
7. ^ ^{a b} Tagami, S; Eguchi Y, Kinoshita M, Takeda M, Tsujimoto Y (Nov. 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. ISSN 0950-9232. PMID 11126360. 

Further reading

• 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. PMID 18330888. 
• 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. PMID 11891768. 
• Watari A, Yutsudo M (2003). "Multi-functional gene ASY/Nogo/RTN-X/RTN4: apoptosis, tumor suppression, and inhibition of neuronal regeneration.". Apoptosis 8 (1): 5–9. doi:10.1023/A:1021639016300. PMID 12510146. 
• Schweigreiter R, Bandtlow CE (2006). "Nogo in the injured spinal cord.". J. Neurotrauma 23 (3-4): 384–96. doi:10.1089/neu.2006.23.384. PMID 16629624. 
• 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. PMID 10048485. 
• Prinjha R, Moore SE, Vinson M, et al. (2000). "Inhibitor of neurite outgrowth in humans.". Nature 403 (6768): 383–4. doi:10.1038/35000287. PMID 10667780. 
• 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.". Nature 403 (6768): 434–9. doi:10.1038/35000219. PMID 10667796. 
• Zhang QH, Ye M, Wu XY, et al. (2001). "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells.". Genome Res. 10 (10): 1546–60. doi:10.1101/gr.140200. PMC 310934. PMID 11042152. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=310934. 
• Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination.". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=310948. 
• 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.". Oncogene 19 (50): 5736–46. doi:10.1038/sj.onc.1203948. PMID 11126360. 
• Fournier AE, GrandPre T, Strittmatter SM (2001). "Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration.". Nature 409 (6818): 341–6. doi:10.1038/35053072. PMID 11201742. 
• 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. PMID 11358445. 
• Zhou ZM, Sha JH, Li JM, et al. (2002). "Expression of a novel reticulon-like gene in human testis.". Reproduction 123 (2): 227–34. doi:10.1530/rep.0.1230227. PMID 11866689. 
• GrandPré T, Li S, Strittmatter SM (2002). "Nogo-66 receptor antagonist peptide promotes axonal regeneration.". Nature 417 (6888): 547–51. doi:10.1038/417547a. PMID 12037567. 
• Hu WH, Hausmann ON, Yan MS, et al. (2002). "Identification and characterization of a novel Nogo-interacting mitochondrial protein (NIMP).". J. Neurochem. 81 (1): 36–45. doi:10.1046/j.1471-4159.2002.00788.x. PMID 12067236. 
• Liu BP, Fournier A, GrandPré T, Strittmatter SM (2002). "Myelin-associated glycoprotein as a functional ligand for the Nogo-66 receptor.". Science 297 (5584): 1190–3. doi:10.1126/science.1073031. PMID 12089450. 
• 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. PMID 12270696. 
• 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. PMID 12377379. 
• 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. PMID 15317586. 
• Li M, Liu J, Song J. (2006). "Nogo goes in the pure water: solution structure of Nogo-60 and design of the structured and buffer-soluble Nogo-54 for enhancing CNS regeneration.". Protein Sci. 15 (8): 1835–41.. doi:10.1110/ps.062306906. PMC 2242580. PMID 16877707. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2242580. 
• 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. PMID 17397058. 
• 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. PMID 17585875.