Reticulon 4: Difference between revisions

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{{Infobox_gene}}
{{PBB_Controls
'''Reticulon 4''', also known as '''Neurite outgrowth inhibitor''' or '''Nogo''',  is a [[protein]] that in humans is encoded by the ''RTN4'' [[gene]]<ref name="pmid10667797">{{cite journal | vauthors = GrandPré T, Nakamura F, Vartanian T, Strittmatter SM | title = Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein | journal = Nature | volume = 403 | issue = 6768 | pages = 439–44 | date = Jan 2000 | pmid = 10667797 | pmc =  | doi = 10.1038/35000226 }}</ref><ref name="pmid10773680">{{cite journal | vauthors = Yang J, Yu L, Bi AD, Zhao SY | title = Assignment of the human reticulon 4 gene (RTN4) to chromosome 2p14-->2p13 by radiation hybrid mapping | journal = Cytogenetics and Cell Genetics | volume = 88 | issue = 1-2 | pages = 101–2 | date = June 2000 | pmid = 10773680 | pmc =  | doi = 10.1159/000015499 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: RTN4 reticulon 4| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=57142| accessdate = }}</ref> that has been identified as an [[Enzyme inhibitor|inhibitor]] of [[neurite]] outgrowth specific to the [[central nervous system]]. During neural development Nogo is expressed mainly by neurons and provides an inhibitory signal for the migration and sprouting of CNS endothelial (tip) cells, thereby restricting blood vessel density.
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
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.<ref name="entrez"/> 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.<ref name=Karnezis2004/>
{{GNF_Protein_box
| image = PBB_Protein_RTN4_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 2g31.
| PDB = {{PDB2|2g31}}
| Name = Reticulon 4
| HGNCid = 14085
| Symbol = RTN4
| AltSymbols =; NSP; ASY; NI220/250; NOGO; NOGO-A; NSP-CL; Nbla00271; Nbla10545; RTN-X; RTN4-A; RTN4-B1; RTN4-B2; RTN4-C
| OMIM = 604475
| ECnumber = 
| Homologene = 10743
| MGIid = 1915835
| GeneAtlas_image1 = PBB_GE_RTN4_211509_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_RTN4_210968_s_at_tn.png
| GeneAtlas_image3 = PBB_GE_RTN4_214629_x_at_tn.png
| Function = {{GNF_GO|id=GO:0005515 |text = protein binding}}
| Component = {{GNF_GO|id=GO:0005635 |text = nuclear envelope}} {{GNF_GO|id=GO:0005783 |text = endoplasmic reticulum}} {{GNF_GO|id=GO:0016020 |text = membrane}} {{GNF_GO|id=GO:0016021 |text = integral to membrane}} {{GNF_GO|id=GO:0030176 |text = integral to endoplasmic reticulum membrane}}
| Process = {{GNF_GO|id=GO:0019987 |text = negative regulation of anti-apoptosis}} {{GNF_GO|id=GO:0030517 |text = negative regulation of axon extension}} {{GNF_GO|id=GO:0042981 |text = regulation of apoptosis}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 57142
    | Hs_Ensembl = ENSG00000115310
    | Hs_RefseqProtein = NP_008939
    | Hs_RefseqmRNA = NM_007008
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 2
    | Hs_GenLoc_start = 55052829
    | Hs_GenLoc_end = 55131468
    | Hs_Uniprot = Q9NQC3
    | Mm_EntrezGene = 68585
    | Mm_Ensembl = ENSMUSG00000020458
    | Mm_RefseqmRNA = NM_024226
    | Mm_RefseqProtein = NP_077188
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 11
    | Mm_GenLoc_start = 29592947
    | Mm_GenLoc_end = 29644255
    | Mm_Uniprot = Q99P72
  }}
}}
'''Reticulon 4''', also known as '''RTN4''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: RTN4 reticulon 4| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=57142| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
Research suggests that blocking Nogo-A during neuronal damage (from diseases such as [[Multiple Sclerosis]]) will help to protect or restore the damaged neurons.<ref name=Karnezis2004>{{cite journal | vauthors = Karnezis T, Mandemakers W, McQualter JL, Zheng B, Ho PP, Jordan KA, Murray BM, Barres B, Tessier-Lavigne M, Bernard CC | title = The neurite outgrowth inhibitor Nogo A is involved in autoimmune-mediated demyelination | journal = Nature Neuroscience | volume = 7 | issue = 7 | pages = 736–44 | date = Jul 2004 | pmid = 15184901 | doi = 10.1038/nn1261 }}</ref><ref>{{cite journal|last1=Sozmen|first1=EG et al|title=Nogo receptor blockade overcomes remyelination failure after white matter stroke and stimulates functional recovery in aged mice|journal=PNAS USA|date=2016|volume=113|pages=E8453–E8462|doi=10.1073/pnas.1615322113|pmc=5206535}}</ref> The investigation into the mechanisms of this protein presents a great potential for the treatment of [[Autoimmune disease|auto-immune]] mediated [[demyelinating diseases]] and [[spinal cord injury]] [[Neuroregeneration|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.<ref>[http://www.eurekalert.org/pub_releases/2008-03/uorm-sar031808.php Stopping a receptor called 'nogo' boosts the synapses]</ref>
{{PBB_Summary
| section_title =  
| summary_text = 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 which 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.<ref name="entrez">{{cite web | title = Entrez Gene: RTN4 reticulon 4| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=57142| accessdate = }}</ref>
}}


==See also==
== Interactions ==
 
Reticulon 4 has been shown to [[Protein-protein interaction|interact]] with [[WWP1]],<ref name=pmid19035836>{{cite journal | vauthors = Qin H, Pu HX, Li M, Ahmed S, Song J | title = Identification and structural mechanism for a novel interaction between a ubiquitin ligase WWP1 and Nogo-A, a key inhibitor for central nervous system regeneration | journal = Biochemistry | volume = 47 | issue = 51 | pages = 13647–58 | date = Dec 2008 | pmid = 19035836 | doi = 10.1021/bi8017976 }}</ref> [[BCL2-like 1 (gene)|BCL2-like 1]]<ref name=pmid11126360>{{cite journal | vauthors = Tagami S, Eguchi Y, Kinoshita M, Takeda M, Tsujimoto Y | title = A novel protein, RTN-XS, interacts with both Bcl-XL and Bcl-2 on endoplasmic reticulum and reduces their anti-apoptotic activity | journal = Oncogene | volume = 19 | issue = 50 | pages = 5736–46 | date = Nov 2000 | pmid = 11126360 | doi = 10.1038/sj.onc.1203948 }}</ref> and [[Bcl-2]].<ref name=pmid11126360/>
 
== See also ==
*[[Reticulon 4 receptor]]
*[[Reticulon 4 receptor]]
==References==
 
{{reflist|2}}
== References ==
==Further reading==
{{reflist}}
 
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Teng FY, Tang BL | title = Cell autonomous function of Nogo and reticulons: The emerging story at the endoplasmic reticulum | journal = Journal of Cellular Physiology | volume = 216 | issue = 2 | pages = 303–8 | date = Aug 2008 | pmid = 18330888 | doi = 10.1002/jcp.21434 }}
| citations =
* {{cite journal | vauthors = Ng CE, Tang BL | title = Nogos and the Nogo-66 receptor: factors inhibiting CNS neuron regeneration | journal = Journal of Neuroscience Research | volume = 67 | issue = 5 | pages = 559–65 | date = Mar 2002 | pmid = 11891768 | doi = 10.1002/jnr.10134 }}
*{{cite journal | author=Ng CE, Tang BL |title=Nogos and the Nogo-66 receptor: factors inhibiting CNS neuron regeneration. |journal=J. Neurosci. Res. |volume=67 |issue= 5 |pages= 559-65 |year= 2002 |pmid= 11891768 |doi= }}
* {{cite journal | vauthors = Watari A, Yutsudo M | title = Multi-functional gene ASY/Nogo/RTN-X/RTN4: apoptosis, tumor suppression, and inhibition of neuronal regeneration | journal = Apoptosis | volume = 8 | issue = 1 | pages = 5–9 | date = Jan 2003 | pmid = 12510146 | doi = 10.1023/A:1021639016300 }}
*{{cite journal | author=Watari A, Yutsudo M |title=Multi-functional gene ASY/Nogo/RTN-X/RTN4: apoptosis, tumor suppression, and inhibition of neuronal regeneration. |journal=Apoptosis |volume=8 |issue= 1 |pages= 5-9 |year= 2003 |pmid= 12510146 |doi= }}
* {{cite journal | vauthors = Schweigreiter R, Bandtlow CE | title = Nogo in the injured spinal cord | journal = Journal of Neurotrauma | volume = 23 | issue = 3-4 | pages = 384–96 | year = 2006 | pmid = 16629624 | doi = 10.1089/neu.2006.23.384 }}
*{{cite journal | author=Schweigreiter R, Bandtlow CE |title=Nogo in the injured spinal cord. |journal=J. Neurotrauma |volume=23 |issue= 3-4 |pages= 384-96 |year= 2006 |pmid= 16629624 |doi= 10.1089/neu.2006.23.384 }}
* {{cite journal | vauthors = Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O | title = 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 | journal = DNA Research | volume = 5 | issue = 6 | pages = 355–64 | date = Dec 1998 | pmid = 10048485 | doi = 10.1093/dnares/5.6.355 }}
*{{cite journal | author=Nagase T, Ishikawa K, Suyama M, ''et al.'' |title=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. |journal=DNA Res. |volume=5 |issue= 6 |pages= 355-64 |year= 1999 |pmid= 10048485 |doi= }}
* {{cite journal | vauthors = Prinjha R, Moore SE, Vinson M, Blake S, Morrow R, Christie G, Michalovich D, Simmons DL, Walsh FS | title = Inhibitor of neurite outgrowth in humans | journal = Nature | volume = 403 | issue = 6768 | pages = 383–4 | date = Jan 2000 | pmid = 10667780 | doi = 10.1038/35000287 }}
*{{cite journal | author=Prinjha R, Moore SE, Vinson M, ''et al.'' |title=Inhibitor of neurite outgrowth in humans. |journal=Nature |volume=403 |issue= 6768 |pages= 383-4 |year= 2000 |pmid= 10667780 |doi= 10.1038/35000287 }}
* {{cite journal | vauthors = Chen MS, Huber AB, van der Haar ME, Frank M, Schnell L, Spillmann AA, Christ F, Schwab ME | title = Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1 | journal = Nature | volume = 403 | issue = 6768 | pages = 434–9 | date = Jan 2000 | pmid = 10667796 | doi = 10.1038/35000219 }}
*{{cite journal | author=Chen MS, Huber AB, van der Haar ME, ''et al.'' |title=Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1. |journal=Nature |volume=403 |issue= 6768 |pages= 434-9 |year= 2000 |pmid= 10667796 |doi= 10.1038/35000219 }}
* {{cite journal | vauthors = Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY, Lu G, Zhong M, Xu XR, Han ZG, Zhang JW, Tao J, Huang QH, Zhou J, Hu GX, Gu J, Chen SJ, Chen Z | title = Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells | journal = Genome Research | volume = 10 | issue = 10 | pages = 1546–60 | date = Oct 2000 | pmid = 11042152 | pmc = 310934 | doi = 10.1101/gr.140200 }}
*{{cite journal | author=GrandPré T, Nakamura F, Vartanian T, Strittmatter SM |title=Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein. |journal=Nature |volume=403 |issue= 6768 |pages= 439-44 |year= 2000 |pmid= 10667797 |doi= 10.1038/35000226 }}
* {{cite journal | vauthors = Hartley JL, Temple GF, Brasch MA | title = DNA cloning using in vitro site-specific recombination | journal = Genome Research | volume = 10 | issue = 11 | pages = 1788–95 | date = Nov 2000 | pmid = 11076863 | pmc = 310948 | doi = 10.1101/gr.143000 }}
*{{cite journal | author=Yang J, Yu L, Bi AD, Zhao SY |title=Assignment of the human reticulon 4 gene (RTN4) to chromosome 2p14-->2p13 by radiation hybrid mapping. |journal=Cytogenet. Cell Genet. |volume=88 |issue= 1-2 |pages= 101-2 |year= 2000 |pmid= 10773680 |doi= }}
* {{cite journal | vauthors = Tagami S, Eguchi Y, Kinoshita M, Takeda M, Tsujimoto Y | title = A novel protein, RTN-XS, interacts with both Bcl-XL and Bcl-2 on endoplasmic reticulum and reduces their anti-apoptotic activity | journal = Oncogene | volume = 19 | issue = 50 | pages = 5736–46 | date = Nov 2000 | pmid = 11126360 | doi = 10.1038/sj.onc.1203948 }}
*{{cite journal | author=Zhang QH, Ye M, Wu XY, ''et al.'' |title=Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells. |journal=Genome Res. |volume=10 |issue= 10 |pages= 1546-60 |year= 2001 |pmid= 11042152 |doi= }}
* {{cite journal | vauthors = Fournier AE, GrandPre T, Strittmatter SM | title = Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration | journal = Nature | volume = 409 | issue = 6818 | pages = 341–6 | date = Jan 2001 | pmid = 11201742 | doi = 10.1038/35053072 }}
*{{cite journal | author=Hartley JL, Temple GF, Brasch MA |title=DNA cloning using in vitro site-specific recombination. |journal=Genome Res. |volume=10 |issue= 11 |pages= 1788-95 |year= 2001 |pmid= 11076863 |doi= }}
* {{cite journal | vauthors = Josephson A, Widenfalk J, Widmer HW, Olson L, Spenger C | title = NOGO mRNA expression in adult and fetal human and rat nervous tissue and in weight drop injury | journal = Experimental Neurology | volume = 169 | issue = 2 | pages = 319–28 | date = Jun 2001 | pmid = 11358445 | doi = 10.1006/exnr.2001.7659 }}
*{{cite journal | author=Tagami S, Eguchi Y, Kinoshita M, ''et al.'' |title=A novel protein, RTN-XS, interacts with both Bcl-XL and Bcl-2 on endoplasmic reticulum and reduces their anti-apoptotic activity. |journal=Oncogene |volume=19 |issue= 50 |pages= 5736-46 |year= 2001 |pmid= 11126360 |doi= 10.1038/sj.onc.1203948 }}
* {{cite journal | vauthors = Zhou ZM, Sha JH, Li JM, Lin M, Zhu H, Zhou YD, Wang LR, Zhu H, Wang YQ, Zhou KY | title = Expression of a novel reticulon-like gene in human testis | journal = Reproduction | volume = 123 | issue = 2 | pages = 227–34 | date = Feb 2002 | pmid = 11866689 | doi = 10.1530/rep.0.1230227 }}
*{{cite journal | author=Fournier AE, GrandPre T, Strittmatter SM |title=Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration. |journal=Nature |volume=409 |issue= 6818 |pages= 341-6 |year= 2001 |pmid= 11201742 |doi= 10.1038/35053072 }}
* {{cite journal | vauthors = GrandPré T, Li S, Strittmatter SM | title = Nogo-66 receptor antagonist peptide promotes axonal regeneration | journal = Nature | volume = 417 | issue = 6888 | pages = 547–51 | date = May 2002 | pmid = 12037567 | doi = 10.1038/417547a }}
*{{cite journal | author=Josephson A, Widenfalk J, Widmer HW, ''et al.'' |title=NOGO mRNA expression in adult and fetal human and rat nervous tissue and in weight drop injury. |journal=Exp. Neurol. |volume=169 |issue= 2 |pages= 319-28 |year= 2001 |pmid= 11358445 |doi= 10.1006/exnr.2001.7659 }}
* {{cite journal | vauthors = Hu WH, Hausmann ON, Yan MS, Walters WM, Wong PK, Bethea JR | title = Identification and characterization of a novel Nogo-interacting mitochondrial protein (NIMP) | journal = Journal of Neurochemistry | volume = 81 | issue = 1 | pages = 36–45 | date = Apr 2002 | pmid = 12067236 | doi = 10.1046/j.1471-4159.2002.00788.x }}
*{{cite journal | author=Zhou ZM, Sha JH, Li JM, ''et al.'' |title=Expression of a novel reticulon-like gene in human testis. |journal=Reproduction |volume=123 |issue= 2 |pages= 227-34 |year= 2002 |pmid= 11866689 |doi= }}
* {{cite journal | vauthors = Liu BP, Fournier A, GrandPré T, Strittmatter SM | title = Myelin-associated glycoprotein as a functional ligand for the Nogo-66 receptor | journal = Science | volume = 297 | issue = 5584 | pages = 1190–3 | date = Aug 2002 | pmid = 12089450 | doi = 10.1126/science.1073031 }}
*{{cite journal | author=GrandPré T, Li S, Strittmatter SM |title=Nogo-66 receptor antagonist peptide promotes axonal regeneration. |journal=Nature |volume=417 |issue= 6888 |pages= 547-51 |year= 2002 |pmid= 12037567 |doi= 10.1038/417547a }}
* {{cite journal | vauthors = Dupuis L, Gonzalez de Aguilar JL, di Scala F, Rene F, de Tapia M, Pradat PF, Lacomblez L, Seihlan D, Prinjha R, Walsh FS, Meininger V, Loeffler JP | title = Nogo provides a molecular marker for diagnosis of amyotrophic lateral sclerosis | journal = Neurobiology of Disease | volume = 10 | issue = 3 | pages = 358–65 | date = Aug 2002 | pmid = 12270696 | doi = 10.1006/nbdi.2002.0522 }}
*{{cite journal | author=Hu WH, Hausmann ON, Yan MS, ''et al.'' |title=Identification and characterization of a novel Nogo-interacting mitochondrial protein (NIMP). |journal=J. Neurochem. |volume=81 |issue= 1 |pages= 36-45 |year= 2002 |pmid= 12067236 |doi= }}
* {{cite journal | vauthors = Taketomi M, Kinoshita N, Kimura K, Kitada M, Noda T, Asou H, Nakamura T, Ide C | title = Nogo-A expression in mature oligodendrocytes of rat spinal cord in association with specific molecules | journal = Neuroscience Letters | volume = 332 | issue = 1 | pages = 37–40 | date = Oct 2002 | pmid = 12377379 | doi = 10.1016/S0304-3940(02)00910-2 }}
*{{cite journal | author=Liu BP, Fournier A, GrandPré T, Strittmatter SM |title=Myelin-associated glycoprotein as a functional ligand for the Nogo-66 receptor. |journal=Science |volume=297 |issue= 5584 |pages= 1190-3 |year= 2002 |pmid= 12089450 |doi= 10.1126/science.1073031 }}
* {{cite journal | vauthors = Li M, Shi J, Wei Z, Teng FY, Tang BL, Song J | title = Structural characterization of the human Nogo-A functional domains. Solution structure of Nogo-40, a Nogo-66 receptor antagonist enhancing injured spinal cord regeneration | journal = European Journal of Biochemistry / FEBS | volume = 271 | issue = 17 | pages = 3512–22 | date = Sep 2004 | pmid = 15317586 | doi = 10.1111/j.0014-2956.2004.04286.x }}
*{{cite journal | author=Dupuis L, Gonzalez de Aguilar JL, di Scala F, ''et al.'' |title=Nogo provides a molecular marker for diagnosis of amyotrophic lateral sclerosis. |journal=Neurobiol. Dis. |volume=10 |issue= 3 |pages= 358-65 |year= 2002 |pmid= 12270696 |doi= }}
* {{cite journal | vauthors = Li M, Liu J, Song J | title = 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 | journal = Protein Science | volume = 15 | issue = 8 | pages = 1835–41 | date = Aug 2006 | pmid = 16877707 | pmc = 2242580 | doi = 10.1110/ps.062306906 }}
*{{cite journal | author=Taketomi M, Kinoshita N, Kimura K, ''et al.'' |title=Nogo-A expression in mature oligodendrocytes of rat spinal cord in association with specific molecules. |journal=Neurosci. Lett. |volume=332 |issue= 1 |pages= 37-40 |year= 2002 |pmid= 12377379 |doi= }}
* {{cite journal | vauthors = Li M, Song J | title = The N- and C-termini of the human Nogo molecules are intrinsically unstructured: bioinformatics, CD, NMR characterization, and functional implications | journal = Proteins | volume = 68 | issue = 1 | pages = 100–8 | date = Jul 2007 | pmid = 17397058 | doi = 10.1002/prot.21385 }}
}}
* {{cite journal | vauthors = Li M, Song J | title = Nogo-B receptor possesses an intrinsically unstructured ectodomain and a partially folded cytoplasmic domain | journal = Biochemical and Biophysical Research Communications | volume = 360 | issue = 1 | pages = 128–34 | date = Aug 2007 | pmid = 17585875 | doi = 10.1016/j.bbrc.2007.06.031 }}
{{refend}}
{{refend}}


{{protein-stub}}
{{PDB Gallery|geneid=57142}}
 
[[Category:Enzyme inhibitors]]

Latest revision as of 07:29, 23 May 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
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View/Edit Human

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. During neural development Nogo is expressed mainly by neurons and provides an inhibitory signal for the migration and sprouting of CNS endothelial (tip) cells, thereby restricting blood vessel density.

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][5] 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.[6]

Interactions

Reticulon 4 has been shown to interact with WWP1,[7] BCL2-like 1[8] and Bcl-2.[8]

See also

References

  1. ↑ GrandPré T, Nakamura F, Vartanian T, Strittmatter SM (Jan 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 (June 2000). "Assignment of the human reticulon 4 gene (RTN4) to chromosome 2p14-->2p13 by radiation hybrid mapping". Cytogenetics and Cell Genetics. 88 (1–2): 101–2. doi:10.1159/000015499. PMID 10773680.
  3. ↑ 3.0 3.1 "Entrez Gene: RTN4 reticulon 4".
  4. ↑ 4.0 4.1 Karnezis T, Mandemakers W, McQualter JL, Zheng B, Ho PP, Jordan KA, Murray BM, Barres B, Tessier-Lavigne M, Bernard CC (Jul 2004). "The neurite outgrowth inhibitor Nogo A is involved in autoimmune-mediated demyelination". Nature Neuroscience. 7 (7): 736–44. doi:10.1038/nn1261. PMID 15184901.
  5. ↑ Sozmen, EG; et al. (2016). "Nogo receptor blockade overcomes remyelination failure after white matter stroke and stimulates functional recovery in aged mice". PNAS USA. 113: E8453–E8462. doi:10.1073/pnas.1615322113. PMC 5206535.
  6. ↑ Stopping a receptor called 'nogo' boosts the synapses
  7. ↑ Qin H, Pu HX, Li M, Ahmed S, Song J (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. 47 (51): 13647–58. doi:10.1021/bi8017976. PMID 19035836.
  8. ↑ 8.0 8.1 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. 19 (50): 5736–46. doi:10.1038/sj.onc.1203948. PMID 11126360.

Further reading

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