Reticulon 4
Encyclopedia
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.
with WWP1
, BCL2-like 1
and Bcl-2
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the RTN4 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
that has been identified as an inhibitor
Enzyme inhibitor
An enzyme inhibitor is a molecule that binds to enzymes and decreases their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...
of neurite
Neurite
A neurite refers to any projection from the cell body of a neuron. This projection can be either an axon or a dendrite. The term is frequently used when speaking of immature or developing neurons, especially of cells in culture, because it can be difficult to tell axons from dendrites before...
outgrowth specific to the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
.
This gene belongs to the family of reticulon
Reticulon
Reticulons are a group of evolutionary conservative proteins residing predominantly in endoplasmic reticulum, primarily playing a role in promoting membrane curvature...
-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
Growth cone
A growth cone is a dynamic, actin-supported extension of a developing axon seeking its synaptic target. Their existence was originally proposed by Spanish histologist Santiago Ramón y Cajal based upon stationary images he observed under the microscope...
destruction.
Research suggests that blocking Nogo-A during neuronal damage (from diseases such as Multiple Sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
) 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
Autoimmune disease
Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...
mediated demyelinating diseases and spinal cord injury
Spinal cord injury
A spinal cord injury refers to any injury to the spinal cord that is caused by trauma instead of disease. Depending on where the spinal cord and nerve roots are damaged, the symptoms can vary widely, from pain to paralysis to incontinence...
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.
Interactions
Reticulon 4 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with WWP1
WWP1
NEDD4-like E3 ubiquitin-protein ligase WWP1 is an enzyme that in humans is encoded by the WWP1 gene.-Interactions:WWP1 has been shown to interact with KLF2, Reticulon 4 and CPSF6.-Further reading:...
, BCL2-like 1
BCL2-like 1 (gene)
Bcl-2-like protein 1 is a protein that in humans is encoded by the BCL2L1 gene.-Interactions:BCL2-like 1 has been shown to interact with RAD9A, RTN1, BAK1, Reticulon 4, Bcl-2-associated X protein, BCAP31, Bcl-2-interacting killer, PPP1CA, Noxa, VDAC1, BCL2L11, Bcl-2-associated death promoter,...
and Bcl-2
Bcl-2
Bcl-2 is the founding member of the Bcl-2 family of apoptosis regulator proteins encoded by the BCL2 gene. Bcl-2 derives its name from B-cell lymphoma 2, as it is the second member of a range of proteins initially described in chromosomal translocations involving chromosomes 14 and 18 in...
.