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RTN4

GeneName

RTN4

Summary

RTN4, also known as Nogo or NSP, is a 130 kDa protein primarily expressed in the nervous system, particularly in neurons. It is localised to various cellular components including the endoplasmic reticulum, synapses, and cell junctions. RTN4 plays a role in several biological processes such as axonal fasciculation, brain development, and the regulation of apoptosis. It is involved in cell adhesion and migration, particularly in the context of vasculogenesis and inflammatory responses. Additionally, RTN4 has functions related to RNA binding and cadherin binding, indicating its involvement in complex cellular interactions and signalling pathways.

Importance

RTN4 is relevant to: - Neural regeneration and repair due to its role in inhibiting axon growth and promoting neuronal stability - Neurodegenerative diseases as it is implicated in the regulation of amyloid-beta formation and neuronal apoptosis - Angiogenesis and vascular development given its involvement in cell migration and adhesion processes - Inflammatory responses through its effects on leukocyte migration and cytokine production

Top Products

For researchers investigating RTN4, we recommend two primary antibodies that stand out for their performance and versatility. The first is the well-cited polyclonal antibody, Anti-Nogo A+B antibody (ab47085), which has garnered 25 citations and is particularly effective in Western blotting (WB) and immunocytochemistry (ICC). This product is a trusted choice for those looking to study RTN4 in detail. Additionally, we offer the recombinant antibody, Anti-Nogo antibody [EPR12265] (ab180847), which has been validated for a broader range of applications, including Western blotting (WB), immunohistochemistry (IHC), immunocytochemistry (ICC), immunoprecipitation (IP), and flow cytometry (FC). With 3 citations, this recombinant antibody provides the batch-to-batch consistency that many researchers require. Together, these antibodies provide robust options for studying RTN4 effectively.

Abcam Product Citation Summary

The use of the Abcam antibody ab62024 for RTN4 detection in rat models highlights its relevance in studies related to middle cerebral artery occlusion (MCAO), a common experimental model for stroke research.

Abcam Product Citation Table

Product Code
Species
Application
Study Context
PMID
ab62024
Rat
WB
MCAO
31920724

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 (By similarity).

Isoform B

N-terminal part, called Am-Nogo-B(1-200), is the functional domain for RTN4B-mediated signaling in endothelial and vascular smooth muscle cells.

Function

Required to induce the formation and stabilization of endoplasmic reticulum (ER) tubules (PubMed:24262037, PubMed:25612671, PubMed:27619977). They regulate membrane morphogenesis in the ER by promoting tubular ER production (PubMed:24262037, PubMed:25612671, PubMed:27619977, PubMed:27786289). They influence nuclear envelope expansion, nuclear pore complex formation and proper localization of inner nuclear membrane proteins (PubMed:26906412). However each isoform have specific functions mainly depending on their tissue expression specificities (Probable).

Isoform A

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. 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 (PubMed:10667797, PubMed:11201742). Regulates the radial migration of cortical neurons via an RTN4R-LINGO1 containing receptor complex (By similarity). Acts as a negative regulator of central nervous system angiogenesis. Inhibits spreading, migration and sprouting of primary brain microvascular endothelial cells (MVECs). Also induces the retraction of MVECs lamellipodia and filopodia in a ROCK pathway-dependent manner (By similarity).

Isoform B

Mainly function in endothelial cells and vascular smooth muscle cells, is also involved in immune system regulation (Probable). Modulator of vascular remodeling, promotes the migration of endothelial cells but inhibits the migration of vascular smooth muscle cells. Regulates endothelial sphingolipid biosynthesis with direct effects on vascular function and blood pressure. Inhibits serine palmitoyltransferase, SPTLC1, the rate-limiting enzyme of the novo sphingolipid biosynthetic pathway, thereby controlling production of endothelial sphingosine-1-phosphate (S1P). Required to promote macrophage homing and functions such as cytokine/chemokine gene expression involved in angiogenesis, arteriogenesis and tissue repair. Mediates ICAM1 induced transendothelial migration of leukocytes such as monocytes and neutrophils and acute inflammation. Necessary for immune responses triggered by nucleic acid sensing TLRs, such as TLR9, is required for proper TLR9 location to endolysosomes. Also involved in immune response to LPS. Plays a role in liver regeneration through the modulation of hepatocytes proliferation (By similarity). 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 (PubMed:11126360). With isoform C, inhibits BACE1 activity and amyloid precursor protein processing (PubMed:16965550).

Isoform C

Regulates cardiomyocyte apoptosis upon hypoxic conditions (By similarity). With isoform B, inhibits BACE1 activity and amyloid precursor protein processing (PubMed:16965550).

Tissue Specificity

Isoform A: is specifically expressed in brain and testis and weakly in heart and skeletal muscle. Isoform B: widely expressed except for the liver. Highly expressed in endothelial cells and vascular smooth muscle cells, including blood vessels and mesenteric arteries (PubMed:15034570, PubMed:21183689). Isoform C: is expressed in brain, skeletal muscle and adipocytes. Isoform D is testis-specific.

Cellular localization

Alternative names

KIAA0886, NOGO, My043, SP1507, RTN4, Reticulon-4, Foocen, Neurite outgrowth inhibitor, Neuroendocrine-specific protein, Neuroendocrine-specific protein C homolog, RTN-x, Reticulon-5, Nogo protein, NSP

swissprot:Q9NQC3 entrezGene:57142 omim:604475

Other research areas