Reticulon 4 receptor


Reticulon 4 receptor
Reticulon 4 receptor

PDB rendering based on 1ozn.
Identifiers
Symbols RTN4R; NGR; NOGOR
External IDs OMIM605566 MGI2136886 HomoloGene11299 GeneCards: RTN4R Gene
Orthologs
Species Human Mouse
Entrez 65078 65079
Ensembl ENSG00000040608 ENSMUSG00000043811
UniProt Q9BZR6 Q99PI8
RefSeq (mRNA) NM_023004 NM_022982.2
RefSeq (protein) NP_075380 NP_075358.1
Location (UCSC) Chr 22:
20.23 – 20.27 Mb
Chr 16:
18.13 – 18.15 Mb
PubMed search [1] [2]

Reticulon 4 receptor (RTN4R) also known as Nogo-66 Receptor (NgR) is a protein which in humans is encoded by the RTN4R gene.[1] This gene encodes the receptor for reticulon 4, oligodendrocytemyelin glycoprotein and myelin-associated glycoprotein. This receptor mediates axonal growth inhibition and may play a role in regulating axonal regeneration and plasticity in the adult central nervous system.[1]

Contents

Function

The Nogo-66 Receptor (NgR) is a high affinity binding receptor for a region of Nogo, a myelin associated protein that inhibits axon outgrowth. NgR was identified by Strittmatter and colleagues[2] using an expression cloning strategy.

NgR is implicated in neuronal plasticity and regeneration. Its relative importance in mediating myelin inhibition in vitro and in vivo is currently under intense investigation, since this protein might be a good drug target for treatment of various neurological conditions such as spinal cord injury and stroke.

Nogo pathway: rho kinase

While the entire pathway is not fully understood, the relationship between NgR and neuronal outgrowth has been fleshed out. NgR is a membrane protein that, when bound to neurite outgrowth inhibitor (Nogo), inhibits cell growth through the activation of rho kinase (ROCK).

NgR activation of p75

It was known that NgR, Nogo, and another membrane receptor called p75 were involved in inhibiting neurite outgrowth. Through a variety of experimental procedures Wang et al.[3] were able to identify the biochemical relationship between NgR and p75. First, it was observed that when p75 was knocked out in mice, outgrowth inhibition was no longer seen. Completing binding assays and co-immunoprecipitations revealed that p75 and NgR were not bound to each other through the cellular membrane. Mutating either p75 or NgR, however, resulted in truncated protein that would help reveal the binding interactions. When the extracellular domains of the receptors were removed no outgrowth inhibition was seen. This would suggest that the receptors interact extracellularly. Furthermore, it was reaffirmed that Nogo and myelin-associated gylcoprotein (MAG) bind NgR and not p75. The receptor p75 lacks a binding domain for either of these proteins.

Activation of rho protein

The work of Kaplan and Miller<[4] shows that there is an interaction between the p75/NgR receptors and Rho GDP dissociation inhibitor (Rho-GDI). Kaplan and Miller show that when Nogo is bound to NgR, Rho-GDI is associated with p75. When Rho-GDI is drawn to p75 it is no longer bound to Rho-GDP. This allows for GTP to be exchanged for GDP activating the Rho protein. Rho-GTP, a Rho GTPase, then activates ROCK which phosphorylates other proteins which inhibit neurite outgrowth. When Nogo is not bound to NgR, p75 is not activated and Rho-GDI remains bound to Rho-GDP. The Rho protein remains bound with GDP and remains inactive. ROCK therefore does not become activated and cannot change transcription patterns to inhibit neuronal outgrowth.

Therapeutic Inhibition

It is reasonable that inhibition of the above mechanism could aid the recovery of those suffering from spinal cord injuries. One such therapy is currently in clinical trials. The drug, called Cethrin, is produced by a group called Alseres. Cethrin is a ROCK inhibitor and therefore acts in the above pathway to prevent the activation of ROCK so neurite outgrowth can occur.[5][6] Cethrin is applied as a paste to the site of injury during decompression surgery.

See also

References

  1. ^ a b "Entrez Gene: RTN4R reticulon 4 receptor". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=65078. 
  2. ^ Fournier AE, GrandPre T, Strittmatter SM (January 2001). "Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration". Nature 409 (6818): 341–6. doi:10.1038/35053072. PMID 11201742. 
  3. ^ Wang KC, Kim JA, Sivasankaran R, Segal R, He Z (November 2002). "P75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG and OMgp". Nature 420 (6911): 74–8. doi:10.1038/nature01176. PMID 12422217. 
  4. ^ Kaplan DR, Miller FD (May 2003). "Axon growth inhibition: signals from the p75 neurotrophin receptor". Nat. Neurosci. 6 (5): 435–6. doi:10.1038/nn0503-435. PMID 12715005. 
  5. ^ Baptiste DC, Fehlings MG (2006). "Pharmacological approaches to repair the injured spinal cord". J. Neurotrauma 23 (3-4): 318–34. doi:10.1089/neu.2006.23.318. PMID 16629619. 
  6. ^ Baptiste DC, Fehlings MG (2007). "Update on the treatment of spinal cord injury". Prog. Brain Res. 161: 217–33. doi:10.1016/S0079-6123(06)61015-7. PMID 17618980. 

Further reading


Wikimedia Foundation. 2010.

Look at other dictionaries:

  • Reticulon 4 — PDB rendering based on 2g31 …   Wikipedia

  • Chromosome 22 (human) — Chromosome 22 is one of the 23 pairs of chromosomes in human cells. Humans normally have two copies of Chromosome 22 in each cell. Chromosome 22 is the second smallest human chromosome, spanning about 49 million DNA base pairs and representing… …   Wikipedia

  • RTN3 — Reticulon 3, also known as RTN3, is a human gene.cite web | title = Entrez Gene: RTN3 reticulon 3| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene Cmd=ShowDetailView TermToSearch=10313| accessdate = ] PBB Summary section title = summary… …   Wikipedia

  • RTN1 — Reticulon 1, also known as RTN1, is a human gene.cite web | title = Entrez Gene: RTN1 reticulon 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene Cmd=ShowDetailView TermToSearch=6252| accessdate = ] PBB Summary section title = summary… …   Wikipedia

  • Nogo-A — …   Wikipedia Español

  • Ретикулон-4 — Обозначения Символы RTN4 Entrez Gene …   Википедия


Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”

We are using cookies for the best presentation of our site. Continuing to use this site, you agree with this.