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
Inhibitor or inhibition may refer to:
In biology
* Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity
* Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotra ...
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.
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
Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This d ...
) will help to protect or restore the damaged neurons.auto-immune
In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". P ...
mediated demyelinating diseases and spinal cord injury regeneration
Regeneration may refer to:
Science and technology
* Regeneration (biology), the ability to recreate lost or damaged cells, tissues, organs and limbs
* Regeneration (ecology), the ability of ecosystems to regenerate biomass, using photosynthesis
...
. It has also been found to be a key player in the process whereby physical exercise enhances learning and memory processes in the brain.[
*] Nogo-A has also been shown to negatively regulate vascular growth and repair following ischemic stroke. Genetic deletion and antibody-mediated blockage of Nogo-A led to enhanced re-vascularization and functional recovery in an experimental mouse model of stroke. Moreover, vascular leakage, a major complication following stroke, was reduced following anti-Nogo-A antibody treatment.
Interactions
Reticulon 4 has been shown to interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with WWP1
NEDD4-like E3 ubiquitin-protein ligase WWP1 is an enzyme that in humans is encoded by the ''WWP1'' gene.
Function
WW domain-containing proteins are found in all eukaryotes and play an important role in the regulation of a wide variety of cellul ...
,[
]
See also
*Reticulon 4 receptor
Reticulon 4 receptor (RTN4R) also known as Nogo-66 Receptor (NgR) or Nogo receptor 1 is a protein which in humans is encoded by the ''RTN4R'' gene. This gene encodes the receptor for reticulon 4, oligodendrocytemyelin glycoprotein and myelin-assoc ...
References
Further reading
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{{PDB Gallery, geneid=57142
Enzyme inhibitors