NOGO-A (RTN4)

NOGO-A is developmental neurite growth regulatory factor with a role as a negative regulator of axon-axon adhesion and growth, and as a facilitator of neurite branching. NOGO-A regulates neurite fasciculation, branching and extension in the developing nervous system. Involved in down-regulation of growth, stabilization of wiring and restriction of plasticity in the adult CNS. NOGO-A regulates the radial migration of cortical neurons via an RTN4R-LINGO1 containing receptor complex. Isoform 2 reduces the anti-apoptotic activity of Bcl-xl and Bcl-2. This is likely consecutive to their change in subcellular location, from the mitochondria to the endoplasmic reticulum, after binding and sequestration. Isoform 2 and isoform 3 inhibit BACE1 activity and amyloid precursor protein processing.

NOGO-A (RTN4) Related Areas

Neuroscience>>Neurodegeneration>>Multiple Sclerosis>>RTN4/NOGO-A

NOGO-A (RTN4) Alternative Names

RTN4, NOGO-A, My043, ASY, NI220/250, NOGO, NOGOC, NSP, NSP-CL, Nbla00271, Nbla10545, Nogo-B, Nogo-C, RTN-X, RTN4-A, RTN4-B1, RTN4-B2, RTN4-C [Homo sapiens]

Rtn4, Nogo-A, RP23-176O5.4, 1110020G17Rik, AA407876, AA409940, AA960376, ASY, C130026I10Rik, KIAA4153, NOGO, NSP-CL, Nogo-B, Nogo-C, mKIAA0886, mKIAA4153 [Mus musculus]

Summaries for NOGO-A (RTN4)

Entrez Gene summary for NOGO-A (RTN4):

RTN4 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 RTN4 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. [provided by RefSeq, Jul 2008]

OMIM - description for NOGO-A (RTN4):

Adult mammalian axon regeneration is generally successful in the peripheral nervous system but poor in the central nervous system. Inhibition results from physical barriers imposed by glial scars, a lack of neurotrophic factors, and growth-inhibitory molecules associated with myelin, the insulating axon sheath. These molecules include NI35, myelin-associated glycoprotein , and Nogo.

Wikipedia summary for NOGO-A (RTN4):

Reticulon-4, also known as Neurite outgrowth inhibitor or Nogo, is a protein that in humans is encoded by the RTN4 gene 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. 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 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.

Human NOGO-A (RTN4) Protein General Information

 

• Protein names: Neurite outgrowth inhibitor
  Short name=Nogo protein
  Short name=NOGO-A
• Sequence length: 1192 AA.
• Domain: Three regions, residues 59-172, 544-725 and the loop 66 amino acids, between the two transmembrane domains, known as Nogo-66 loop, appear to be responsible for the inhibitory effect on neurite outgrowth and the spreading of neurons. This Nogo-66 loop, mediates also the binding of RTN4 to its receptor .
• Sequence similarities: Contains 1 reticulon domain.
• Sequence caution: The sequence AAD39920.1 differs from that shown. Reason: Frameshift at positions 1149 and 1156.
  The sequence AAG43160.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.
  The sequence AAG43160.1 differs from that shown. Reason: Frameshift at positions 684 and 700.
  The sequence BAA74909.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.
• Subunit structure: Binds to RTN4R. Interacts with Bcl-xl and Bcl-2. Isoform 2 binds to NGBR and RTN3. Isoform 2 and isoform 3 interact with BACE1 and BACE2. Interacts with RTN4IP1. Interacts with ATL1.
• Subcellular location: Endoplasmic reticulum membrane; Multi-pass membrane protein. Note: Anchored to the membrane of the endoplasmic reticulum through 2 putative transmembrane domains.
• Tissue specificity: Isoform 1 is specifically expressed in brain and testis and weakly in heart and skeletal muscle.
  Isoform 2 is widely expressed except for the liver.
  Isoform 3 is expressed in brain, skeletal muscle and adipocytes. Isoform 4 is testis-specific.

General information above from UniProt

Function for NOGO-A (RTN4) Protein

UniProtKB:

NOGO-A is developmental neurite growth regulatory factor with a role as a negative regulator of axon-axon adhesion and growth, and as a facilitator of neurite branching. NOGO-A regulates neurite fasciculation, branching and extension in the developing nervous system. Involved in down-regulation of growth, stabilization of wiring and restriction of plasticity in the adult CNS. NOGO-A regulates the radial migration of cortical neurons via an RTN4R-LINGO1 containing receptor complex. Isoform 2 reduces the anti-apoptotic activity of Bcl-xl and Bcl-2. This is likely consecutive to their change in subcellular location, from the mitochondria to the endoplasmic reticulum, after binding and sequestration. Isoform 2 and isoform 3 inhibit BACE1 activity and amyloid precursor protein processing.

Genatlas:

• NOGO-A is neurite outgrow inhibitor, limiting axonal regeneration after nervous injury
• NOGO-A roles central in sporadic and familial amyotrophic lateral sclerosis
• NOGO-A is multidomain protein containing several discrete regions with growth inhibitory functions
• NOGO-A regulates, in association with RTN4R, CNS axonal plasticity and recovery from injury
• NOGO-A can modulate the anti-apoptotic activity of BCL2L1 and BCL2 by binding with them and can change their localization to the ER
• NOGO-A participates in the neuronal responses stemming from hippocampal formation during senescence, and particularly in Alzheimer disease
• RTN4 and MAG are differently involved in oligodendrocyte maturation , suggesting that RTN4 may influence also remyelination in pathological conditions such as multiple sclerosis
• N terminus of Nogo-B promotes the migration of endothelial cells but inhibits the migration of vascular smooth muscle cells
• Nogo-B is a regulator of vascular homeostasis
• Nogo A is involved in central nervous system autoimmune demyelination
• Role of Nogo-A for myelin formation in the developing optic nerve
• NOGO-A is endogenous regulator of inflammatory tissue remodeling and wound healing that is mediated, in part, via impaired macrophage homing to ischemic tissue and wounds
• NOGO-A roles in neuronal migration
• Neuronal form plays an important role in regulating cytoskeletal re-organization without the requirement of signaling through its cognate receptor (RTN4R)
• NOGO-A is developmental neurite growth regulatory factor with a role as a negative regulator of axon-axon adhesion and growth, and as a facilitator of neurite branching
• NOGO-A plays a major role in stabilizing and maintaining the architecture of hippocampal pyramidal neurons
• NOGO-A functions as a negative regulator of neuronal growth, leading to stabilization of the CNS wiring at the expense of extensive plastic rearrangements and regeneration after injury
• NOGO-A may have roles in the regulation of endoplasmic reticulum (ER) structure, processing of amyloid precursor protein and cell survival
• Physiological roles of RTN4, MAG, OMG in processes, such as development, neuronal homeostasis, plasticity, and neurodegeneration
• Endothelial RTN4 regulates leukocyte transmigration and intercellular adhesion molecule-1 (ICAM1)-dependent signaling, and acute inflammation

Homology for human NOGO-A (RTN4)

• ortholog to Rtn4, Rattus norvegicus
• ortholog to Rtn4, Mus musculus
• ortholog to RTN4, Pan troglodytes
• homolog to RTN1, RTN2 and RTN3