Reticulon 4, also known as Neurite outgrowth inhibitor or Nogo, is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''RTN4''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
that has been identified as an
inhibitor of
neurite outgrowth specific to the
central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...
. 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 Reticulons (RTNs in vertebrates and reticulon-like proteins or RNTls in other eukaryotes) are a group of conserved sequence, evolutionary conservative proteins residing predominantly in endoplasmic reticulum, primarily playing a role in promoting li ...
-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
A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have uniqu ...
: 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
A growth cone is a large actin-supported extension of a developing or regenerating neurite seeking its synaptic target. It is the growth cone that drives axon growth. Their existence was originally proposed by Spanish histologist Santiago ...
destruction.
[
Research suggests that blocking Nogo-A during neuronal damage (from diseases such as ]multiple sclerosis
Multiple sclerosis (MS) is an autoimmune disease resulting in damage to myelinthe insulating covers of nerve cellsin the brain and spinal cord. As a demyelinating disease, MS disrupts the nervous system's ability to Action potential, transmit ...
) will help to protect or restore the damaged neurons.spinal cord injury
A spinal cord injury (SCI) is damage to the spinal cord that causes temporary or permanent changes in its function. It is a destructive neurological and pathological state that causes major motor, sensory and autonomic dysfunctions.
Symptoms of ...
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.[
*] 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 with WWP1,[
]
See also
* Reticulon 4 receptor
References
Further reading
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
{{PDB Gallery, geneid=57142
Enzyme inhibitors