Affinage

RTN4

Reticulon-4 · UniProt Q9NQC3

Length
1192 aa
Mass
129.9 kDa
Annotated
2026-06-10
100 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RTN4/Nogo is a multifunctional reticulon expressed as several isoforms (Nogo-A/B/C) that acts both as a cell-surface inhibitory ligand restraining neuronal growth and plasticity and as an endoplasmic reticulum morphoregulator (PMID:11201742, PMID:12843238, PMID:38955182). Its principal extracellular activity resides in three distinct inhibitory regions of Nogo-A: an N-terminal region that inhibits fibroblast spreading, a Nogo-A-specific (Δ20) domain, and the C-terminal Nogo-66 loop that collapses growth cones (PMID:12843238). The Nogo-66 loop binds the GPI-anchored leucine-rich-repeat receptor NgR, whose LRR domain is necessary and sufficient for ligand binding while its C-terminal region transduces inhibition; soluble or peptide-competitive (NEP1-40) antagonists of NgR relieve myelin- and Nogo-mediated outgrowth inhibition (PMID:11201742, PMID:12388594, PMID:12037567). The Nogo-A-Δ20 domain signals through a separate axis, binding the GPCR S1PR2 (coupled to G13/LARG/RhoA) and, independently, heparan sulfate proteoglycans syndecan-3/4 to activate RhoA, inhibit cell spreading, and restrict neurite outgrowth and hippocampal LTP (PMID:24453941, PMID:28943240). Downstream effectors of this signaling include RhoA-ROCK and MEK-MAPK pathways that suppress AMPA/NMDA receptor and PSD95 expression via mTOR-dependent translation, CRMP-2 phosphorylation at Thr555 driving axonal degeneration, and rapid F-actin remodeling at dendritic spines (PMID:21985178, PMID:22544872, PMID:26748478). Genetic deletion of Nogo-A or NgR1 promotes compensatory axonal sprouting and motor recovery and enhances LTP, establishing these proteins as endogenous brakes on CNS plasticity (PMID:17122049, PMID:21262805). Conversely, RTN4 receptors (NgR1/2/3) serve as high-affinity ligands for BAI adhesion-GPCRs through glycosylated TSR domains, controlling dendritic arborization, axon elongation, and synapse formation (PMID:34758294). Within the ER, RTN4 narrows tubule diameter in proportion to its expression level, limiting luminal Ca2+ transport to the cell periphery and thereby suppressing neurite outgrowth in a cell-autonomous manner (PMID:38955182). RTN4-B/C also interact with BACE1 to inhibit amyloid-β production (PMID:16965550), and isoform-specific roles outside the nervous system include Nogo-C-driven cardiomyocyte apoptosis and Nogo-A negative regulation of serine palmitoyltransferase to restrain ceramide biosynthesis under cardiac stress (PMID:27763637, PMID:35815623).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2001 High

    Established that a defined extracellular fragment of Nogo (Nogo-66) inhibits axon growth through a specific GPI-anchored receptor, converting myelin inhibition from a phenomenon into a receptor-ligand mechanism.

    Evidence Binding assays, GPI cleavage, and NgR expression rescue in neurons with outgrowth readouts

    PMID:11201742

    Open questions at the time
    • Did not identify the signal-transducing co-receptors
    • Did not resolve how NgR couples to intracellular effectors
  2. 2002 High

    Resolved the structure-function division of NgR—that the LRR domain binds ligand while the C-terminus signals—and showed a soluble NgR antagonizes inhibition, validating the receptor as a therapeutic target.

    Evidence Domain mutagenesis, alkaline-phosphatase binding assays, and competitive NEP1-40 peptide in vitro and in spinal cord injury models

    PMID:12037567 PMID:12388594

    Open questions at the time
    • Mechanism of NgR multimerization and downstream coupling not defined
    • Fraction of myelin inhibition independent of NgR unquantified
  3. 2003 High

    Defined Nogo-A as carrying three independent inhibitory domains accessible at the oligodendrocyte surface, establishing that Nogo inhibition is not solely Nogo-66/NgR-mediated.

    Evidence Recombinant fragment functional assays, surface biotinylation, and topology immunofluorescence in oligodendrocytes

    PMID:12843238

    Open questions at the time
    • Receptors for the N-terminal and Δ20 domains were not yet known
    • Membrane topology of surface Nogo-A only partially resolved
  4. 2006 High

    Showed RTN4-B/C physically engage BACE1 and reduce amyloid-β production, linking reticulons to amyloid processing in the secretory pathway.

    Evidence Proteomics, reciprocal Co-IP, and Aβ secretion assays with domain-mapping in SH-SY5Y/HEK293 cells

    PMID:16965550

    Open questions at the time
    • Physiological relevance in neurons in vivo not established
    • Whether endogenous RTN4 levels regulate BACE1 not tested
  5. 2006 High

    Demonstrated genetic deletion of Nogo-A/NgR1 enhances axonal sprouting and motor recovery in vivo, proving these proteins are endogenous restrictors of CNS plasticity rather than purely in vitro inhibitors.

    Evidence nogo-ab and ngr1 knockout mice with pyramidotomy, anterograde CST tracing, and behavioral motor testing

    PMID:17122049

    Open questions at the time
    • Did not dissect cell-type-specific contributions
    • Did not identify which receptors mediate the in vivo effect
  6. 2011 High

    Established Nogo-A as a fast-acting brake on adult synaptic plasticity, showing antibody and genetic loss-of-function both elevate LTP and implicating GABAergic regulation.

    Evidence Hippocampal LTP electrophysiology in WT and NogoA KO mice with function-blocking antibodies and GABAA blockade

    PMID:21262805

    Open questions at the time
    • Receptor and downstream effector for the rapid LTP effect not pinned in this study
    • Did not address structural plasticity
  7. 2011 Medium

    Placed Nogo-A/NgR1 signaling on Rho-ROCK and MEK-MAPK cascades controlling glutamate receptor levels via mTOR-dependent translation, providing a molecular route from receptor to synaptic composition.

    Evidence siRNA knockdown, soluble NgR treatment, and pharmacological inhibitor panel with receptor-subunit Western blots

    PMID:21985178

    Open questions at the time
    • Single-lab pathway dissection
    • Direct mTOR target for receptor-subunit translation not identified
  8. 2012 Medium

    Identified CRMP-2 Thr555 phosphorylation as a downstream effector of Nogo-A/NgR1 driving axonal degeneration, connecting the receptor to a cytoskeletal regulator.

    Evidence ngr1 KO EAE model, AAV-T555A-CRMP-2 rescue in retinal ganglion cells, and anti-Nogo antibody treatment

    PMID:22544872

    Open questions at the time
    • Kinase linking NgR1 to CRMP-2 not defined
    • Single lab
  9. 2014 High

    Identified S1PR2 as the specific receptor for the Nogo-A-Δ20 domain, signaling through G13/LARG/RhoA to inhibit outgrowth and LTP, resolving a long-standing missing receptor.

    Evidence Receptor binding, Co-IP, neurite/spreading assays, and LTP recordings in WT and Nogo-A KO mice with pharmacological blockade

    PMID:24453941

    Open questions at the time
    • Did not exclude additional Δ20 receptors
    • Tissue distribution of S1PR2-mediated effects incomplete
  10. 2014 Medium

    Revealed opposing cell-type-specific roles for Nogo-A—oligodendrocyte deletion promotes regrowth while neuronal deletion reduces sprouting—implicating neuronal cis-interactions distinct from trans-inhibition.

    Evidence Cnp-Cre and Thy1-Cre conditional KO lines and AAV2.Cre with optic nerve crush and anterograde tracing

    PMID:25257170

    Open questions at the time
    • Molecular basis of proposed cis-interaction not demonstrated
    • Single lab
  11. 2017 High

    Established heparan sulfate proteoglycans syndecan-3/4 as a second, S1PR2-independent receptor system for Nogo-A-Δ20, broadening the receptor repertoire for this domain.

    Evidence Heparin/HS binding, HSPG knockdown/knockout, RhoA activity, and neurite/spreading/explant assays

    PMID:28943240

    Open questions at the time
    • Relative contribution of HSPG versus S1PR2 in vivo unquantified
    • Whether syndecans act as co-receptors or independent receptors not fully resolved
  12. 2021 High

    Inverted the ligand-receptor logic by showing RTN4 receptors are themselves high-affinity ligands for BAI adhesion-GPCRs via glycosylated TSR domains, controlling dendrite, axon, and synapse development.

    Evidence Unbiased interaction screen, 1.65 Å crystal structure of BAI1/RTN4-receptor complex, affinity measurements, and human neuron loss-of-function assays

    PMID:34758294

    Open questions at the time
    • Downstream BAI signaling from this interaction not detailed
    • Interplay with classic RTN4-ligand signaling unexplored
  13. 2024 High

    Defined a cell-autonomous, receptor-independent mechanism whereby RTN4 narrows ER tubules to restrict luminal Ca2+ delivery and thereby suppress neurite outgrowth, separating its membrane-shaping role from its ligand role.

    Evidence Live ER transport imaging, optogenetic Ca2+ dynamics, in silico ER modeling, and RTN4 gain/loss-of-function in human cortical neurons

    PMID:38955182

    Open questions at the time
    • Link between ER Ca2+ restriction and specific growth signaling not mapped
    • Isoform contributions to tubule narrowing not separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RTN4's distinct activities—extracellular inhibitory ligand, RTN4-receptor ligand-for-BAI role, and ER morphoregulator—are coordinated within and across cell types, and how isoform-specific functions are partitioned, remains unresolved.
  • Integration of surface signaling and ER membrane-shaping roles unknown
  • Isoform-specific receptor/effector assignments incomplete
  • Non-neuronal roles (cardiac, vascular, cancer) mechanistically separate from CNS roles

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0098772 molecular function regulator activity 3 GO:0005198 structural molecule activity 1
Localization
GO:0005783 endoplasmic reticulum 5 GO:0005886 plasma membrane 3 GO:0005634 nucleus 1
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-162582 Signal Transduction 4 R-HSA-1266738 Developmental Biology 3 R-HSA-9612973 Autophagy 2
Partners
BACE1BAI1NGR1ROCK1RTN3S1PR2SDC3SDC4

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 A 66-amino acid extracellular domain of Nogo (Nogo-66) inhibits axonal extension through binding to a brain-specific, leucine-rich-repeat GPI-anchored receptor (NgR/Nogo-66 receptor). Cleavage of GPI-linked proteins from axonal surfaces renders neurons insensitive to Nogo-66, and NgR expression is sufficient to impart Nogo-66 inhibition to otherwise unresponsive neurons. Binding assays, GPI cleavage experiments, viral expression of NgR in neurons, axon outgrowth assays Nature High 11201742
2002 Nogo-66 receptor (NgR) leucine-rich repeat domain is necessary and sufficient for Nogo-66 binding and NgR multimerization; the NgR C-terminal domain is required for inhibitory signaling but not ligand binding; a soluble truncated NgR antagonizes outgrowth inhibition on myelin and Nogo substrates. Alkaline phosphatase-Nogo binding assay in COS-7 cells, viral infection of chick retinal ganglion cells with mutated NgR constructs, neurite outgrowth assays The Journal of Neuroscience High 12388594
2002 A competitive antagonist peptide derived from the N-terminal 40 residues of Nogo-66 (NEP1-40) blocks Nogo-66- and CNS myelin-mediated inhibition of axonal outgrowth in vitro via NgR, demonstrating that NgR mediates a significant portion of myelin inhibition. In vitro axon outgrowth assay with NEP1-40 peptide; intrathecal administration in rat spinal cord hemisection model Nature High 12037567
2003 Nogo-A contains three distinct inhibitory regions: (1) an N-terminal region inhibiting fibroblast spreading, (2) a Nogo-A-specific exon-encoded stretch that restricts neurite outgrowth and induces growth cone collapse, and (3) the C-terminal Nogo-66 loop with growth cone collapsing function. Nogo-A is accessible at the cell surface of living oligodendrocytes via two proposed membrane topology variants. Cell spreading and neurite outgrowth assays with recombinant fragments; surface biotinylation of living oligodendrocytes; selective plasma membrane permeabilization immunofluorescence The Journal of Neuroscience High 12843238
2006 RTN4-B (Nogo-B) and RTN4-C physically interact with BACE1 via the BACE1 transmembrane region; overexpression of RTN4-B/C or RTN3 reduces Aβ40 and Aβ42 secretion by ~30–50% from cells expressing Swedish mutant APP, inhibiting BACE1 activity upstream of the β-C-terminal fragment cleavage step. Proteomic identification in SH-SY5Y cells, co-immunoprecipitation in SH-SY5Y and HEK293 cells, Aβ secretion assays with overexpression of reticulons and BACE1 ectodomain deletion mutant The European Journal of Neuroscience High 16965550
2014 The G protein-coupled receptor sphingosine 1-phosphate receptor 2 (S1PR2) is a specific receptor for the Nogo-A-Δ20 domain. Nogo-A-Δ20 binds S1PR2 at sites distinct from the sphingosine 1-phosphate binding pocket and signals via G13, the Rho GEF LARG, and RhoA to inhibit neurite outgrowth and suppress LTP. Deleting or blocking S1PR2 counteracts Nogo-A-Δ20-mediated inhibition, and S1PR2 blockade enhances LTP in wild-type but not Nogo-A−/− mice. Receptor binding assays, Co-IP, neurite outgrowth assay, cell spreading assay, LTP recordings in hippocampal slices of WT and Nogo-A KO mice, pharmacological blockade PLoS Biology High 24453941
2017 The Nogo-A-Δ20 extracellular domain binds heparin and brain-derived heparan sulfate glycosaminoglycans (but not chondroitin sulfate GAGs); heparan sulfate proteoglycans (HSPGs), specifically syndecan-3 and syndecan-4, are functional receptors for Nogo-A-Δ20 mediating RhoA activation, inhibition of cell spreading, adhesion, and neurite outgrowth independently of S1PR2. Heparin-binding assay, HSPG knockdown/knockout in cell lines and neurons, neurite outgrowth and cell-spreading assays, RhoA activity assay, explant migration assay Developmental Cell High 28943240
2021 RTN4 receptors (NgR1/2/3) are high-affinity ligands for BAI adhesion-GPCRs. A single thrombospondin type 1-repeat (TSR) domain of BAIs binds the leucine-rich repeat domain of all three RTN4-receptor isoforms with nanomolar affinity. C-mannosylation of tryptophan and O-fucosylation of threonine in BAI TSR domains create the binding interface. In human neurons, RTN4 receptors regulate dendritic arborization, axonal elongation, and synapse formation through differential binding to glial versus neuronal BAIs. Unbiased interaction screen, 1.65 Å crystal structure of BAI1/RTN4-receptor complex, affinity measurements, human neuron loss-of-function experiments (dendritic arborization, axon elongation, synapse formation assays) Cell High 34758294
2024 RTN4/Nogo acts as an ER morphoregulator: it narrows ER tubule diameter in proportion to its expression level, thereby limiting ER luminal transport and Ca2+ release. Excess RTN4 inhibits neurite outgrowth in human cortical neurons and restricts ER luminal Ca2+ delivery to the periphery, while RTN4 elimination reverses these effects. Live ER transport visualization, optogenetic Ca2+ dynamics imaging, in silico ER modeling, RTN4 overexpression and knockout in human cortical neurons, neurite outgrowth assays Cell Reports High 38955182
2001 Ectopic expression of ASY/Nogo-B (RTN4-B) induces apoptosis preferentially in cancer cells; transcription of ASY is suppressed in small cell lung cancer, suggesting a role in tumor suppression. The protein targets to the endoplasmic reticulum. Ectopic expression in cell lines, apoptosis assay, RT-PCR of cancer vs. normal tissue Oncogene Medium 11494121
2003 ASY/Nogo-B physically associates with ASYIP (identical to RTN3) via their hydrophobic transmembrane regions; both proteins co-localize in the ER. This interaction was identified by yeast two-hybrid and confirmed by Co-IP in human cells. Yeast two-hybrid screen, co-immunoprecipitation in human cells, immunofluorescence colocalization, mutational analysis of hydrophobic domains Journal of Cellular Physiology Medium 12811824
2006 Nogo-B/ASY overexpression induces apoptosis through ER stress, specifically via ER Ca2+ depletion and ER-specific apoptotic signaling pathways. Stable transfection overexpression, Ca2+ measurement, ER stress marker assays, apoptosis assays with ER stress pathway inhibitors Experimental Cell Research Medium 16687140
2007 Neuronal Nogo-A in cerebellar Purkinje cells destabilizes inhibitory synapses: transgenic overexpression of Nogo-A in Purkinje cells caused progressive disassembly and loss of inhibitory terminals, preceded by downregulation of postsynaptic scaffold proteins spectrin, spectrin-E, and β-catenin, leading to motor learning and coordination deficits. Transgenic mouse lines overexpressing Nogo-A in Purkinje cells, immunohistochemistry for synaptic markers, behavioral motor testing Brain Cell Biology Medium 17957480
2011 Nogo-A restricts synaptic plasticity (LTP) in the adult hippocampus on a fast time scale. Function-blocking anti-Nogo-A antibodies, anti-NgR1 antibodies, and NogoA KO mice all significantly increased LTP; GABAergic blockade restored normal LTP in the absence of NogoA signaling. Baseline transmission and LTD were unaffected. LTP electrophysiology in hippocampal slices from WT, NogoA KO mice; application of function-blocking antibodies; GABAA receptor blockade PNAS High 21262805
2011 Neuronal Nogo-A expression in hippocampal neurons is regulated by signaling through NgR1 via Rho-ROCK and MEK-MAPK pathways; reducing Nogo-A by siRNA increases PSD95, GluA1/GluA2 AMPA, and GluN1/GluN2A/GluN2B NMDA receptor subunits through an mTOR-dependent translation mechanism. siRNA knockdown of Nogo-A and NgR1, soluble NgR fragment treatment, pharmacological inhibition of Rho-ROCK, MEK-MAPK, and mTOR signaling; Western blot quantification of receptor subunits Journal of Neurochemistry Medium 21985178
2016 Nogo-A signaling rapidly modulates F-actin stability at dendritic spines within minutes (acute Nogo-A loss-of-function transiently increases F-actin stability and spine density/length) and restricts AMPAR insertion and mEPSC amplitude at hippocampal CA3 synapses. Acute antibody-mediated Nogo-A blockade in hippocampal slices, F-actin imaging, spine morphology analysis, mEPSC recording Hippocampus Medium 26748478
2009 Neuronal Nogo-A is upregulated after axonal injury or CNS myelin exposure through RhoA activation, and neuronal Nogo-A itself inhibits neurite growth; siRNA knockdown of neuronal Nogo-A markedly increases neurite outgrowth. Soluble NgR (NgSR) prevents RhoA activation by myelin and decreases neuronal Nogo-A levels. siRNA knockdown, herpes simplex virus vector expressing soluble NgR fragment, RhoA activity assay, neurite outgrowth assay, in vivo dorsal root injury model with behavioral assessment The Journal of Biological Chemistry Medium 19901030
2010 Nogo-B (RTN4-B) and its receptor NgBR are required for angiogenesis in zebrafish; NgBR knockdown abolishes Nogo-B-stimulated endothelial cell migration and reduces VEGF-stimulated Akt phosphorylation; constitutively active Akt rescues NgBR knockdown phenotypes, placing Akt downstream of NgBR in Nogo-B- and VEGF-coordinated intersomitic vessel sprouting. Morpholino knockdown in zebrafish, cell migration assay, Akt phosphorylation Western blot, constitutively active Akt rescue Blood Medium 20813898
2022 RTN4/Nogo-A signals via S1PR2 to activate ROCK1-mediated phosphorylation of BECN1 at Thr119, promoting autophagic flux in thalamic vessels after cerebral infarction and thereby suppressing angiogenesis and secondary neural repair. Knockdown of Rtn4 reduces MAP1LC3B-II conversion, BECN1, and SQSTM1 in vessels, coinciding with enhanced angiogenesis. siRNA knockdown of Rtn4, S1PR2 pharmacological activation/inhibition, lentiviral approaches, Western blot for autophagy markers, Co-IP for ROCK1-BECN1 interaction, phosphorylation assays, in vivo MCAO model Autophagy Medium 35263212
2016 Nogo-C expression is upregulated in mouse hearts after myocardial infarction and in hypoxia; adenoviral overexpression of Nogo-C induces cardiomyocyte apoptosis, while shRNA knockdown protects against hypoxia-induced apoptosis. Nogo-C KO mice show improved cardiac function and reduced infarct area after MI. Adenoviral overexpression, shRNA knockdown, Nogo-C KO mouse model, cardiac function assessment, apoptosis assays Cell Death & Disease Medium 27763637
2023 Nogo-A is a negative regulator of serine palmitoyltransferase (SPT) activity in cardiomyocytes, restraining ceramide de novo biosynthesis under hemodynamic stress. Cardiomyocyte-specific Nogo-A KO mice show upregulated SPT activity, ceramide accrual, suppression of 'beneficial' autophagy, worse cardiac hypertrophy, and ~50% mortality after transverse aortic constriction. Cardiomyocyte-specific Nogo-A KO mouse, TAC model, SPT activity assay, ceramide mass spectrometry, autophagy flux assessment Cardiovascular Research Medium 35815623
2018 RTN4 (Nogo) knockdown in cancer cells reduces sphingomyelin synthesis and impairs plasma membrane localization and phosphorylation of AKT in a sphingolipid-dependent manner, without affecting upstream AKT kinases; this retards cancer cell proliferation and tumor xenograft growth, and destabilizes tubulin. siRNA knockdown of RTN4, mass spectrometry proteomics, AKT phosphorylation and membrane fractionation Western blot, sphingomyelin synthesis assay, tumor xenograft model, cytotoxicity assay Molecular Therapy Medium 30078441
2003 Nogo-A is detected in neuronal nuclei (at chromatin), at the rough ER and polyribosomes in the perikaryon, and at/beneath the plasma membrane by immunogold electron microscopy and cell fractionation; nuclear localization was confirmed by Nogo-A transfection in COS-7L cells. Western blot of subcellular fractions, immunohistochemistry, immunogold electron microscopy, COS-7L transfection The Journal of Comparative Neurology Medium 12577319
2012 Phosphorylation of CRMP-2 at Thr555 is downstream of NgR1 activation in experimental autoimmune encephalomyelitis; ngr1 KO mice show reduced pThr555-CRMP-2 and limited axonal degeneration. AAV-mediated expression of a T555A-CRMP-2 mutant in retinal ganglion cells limits optic nerve axonal degeneration, placing CRMP-2 phosphorylation as a downstream effector of Nogo-A/NgR1 signaling. ngr1 KO mouse EAE model, AAV-T555A-CRMP-2 rescue, immunohistochemistry, anti-Nogo antibody treatment Brain Medium 22544872
2014 Cell-type-specific conditional KO shows opposing roles: oligodendrocyte-specific Nogo-A deletion enhances axonal regrowth after optic nerve crush, while neuron-specific deletion of Nogo-A in retinal ganglion cells decreases axon sprouting. This suggests neuronal Nogo-A may promote sprouting through cis-interaction with Nogo receptors at the neuronal membrane, counteracting trans-Nogo-A inhibition. Conditional KO mouse lines (Cnp-Cre and Thy1-Cre), AAV2.Cre injection in Rtn4flox/flox mice, optic nerve crush, anterograde tracing of axonal regrowth Cell Death and Differentiation Medium 25257170
2006 Genetic deletion of both nogo-ab alleles or ngr1 in mice promotes compensatory sprouting of uninjured corticospinal tract axons after pyramidotomy, with associated recovery of fine motor skills, establishing that Nogo-A and NgR1 limit axonal growth and plasticity in vivo. nogo-ab and ngr1 knockout mice, unilateral pyramidotomy, anterograde tracing of CST sprouting, behavioral assessment of forelimb motor skill The Journal of Neuroscience High 17122049
2018 In platelets, RTN4 is phosphorylated downstream of a p38-MK2 signaling axis; this p38-MK2-RTN4 pathway is associated with regulation of Bcl-xl at the ER and with platelet phosphatidylserine exposure (procoagulant phenotype). Pathway and interactome analysis of phosphoproteomics data, in vitro kinase/phosphorylation validation, platelet activation assays with p38/MK2 inhibitors, phosphatidylserine exposure assay American Journal of Physiology. Cell Physiology Low 29412690

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration. Nature 899 11201742
2002 Nogo-66 receptor antagonist peptide promotes axonal regeneration. Nature 569 12037567
2004 Nogo and axon regeneration. Current opinion in neurobiology 482 15018947
2003 Nogo-A inhibits neurite outgrowth and cell spreading with three discrete regions. The Journal of neuroscience : the official journal of the Society for Neuroscience 326 12843238
2010 Functions of Nogo proteins and their receptors in the nervous system. Nature reviews. Neuroscience 318 21045861
2014 Nogo limits neural plasticity and recovery from injury. Current opinion in neurobiology 292 24632308
2003 The Nogo-66 receptor: focusing myelin inhibition of axon regeneration. Trends in neurosciences 260 12689770
2003 Nogo and its paRTNers. Trends in cell biology 221 12667756
2002 Truncated soluble Nogo receptor binds Nogo-66 and blocks inhibition of axon growth by myelin. The Journal of neuroscience : the official journal of the Society for Neuroscience 173 12388594
2012 The role of Nogo-A in axonal plasticity, regrowth and repair. Cell and tissue research 145 22588543
2014 The sphingolipid receptor S1PR2 is a receptor for Nogo-a repressing synaptic plasticity. PLoS biology 144 24453941
2000 Nogo-A, a potent inhibitor of neurite outgrowth and regeneration. Biological chemistry 131 10937871
2006 The Nogo-Nogo receptor pathway limits a spectrum of adult CNS axonal growth. The Journal of neuroscience : the official journal of the Society for Neuroscience 123 17122049
2005 Nogo-A and nogo receptor expression in demyelinating lesions of multiple sclerosis. Journal of neuropathology and experimental neurology 113 15751227
2006 Reticulons RTN3 and RTN4-B/C interact with BACE1 and inhibit its ability to produce amyloid beta-protein. The European journal of neuroscience 111 16965550
2001 Link of a new type of apoptosis-inducing gene ASY/Nogo-B to human cancer. Oncogene 102 11494121
2011 NogoA restricts synaptic plasticity in the adult hippocampus on a fast time scale. Proceedings of the National Academy of Sciences of the United States of America 100 21262805
2002 The Nogo receptor, its ligands and axonal regeneration in the spinal cord; a review. Journal of neurocytology 100 12815233
2012 Limiting multiple sclerosis related axonopathy by blocking Nogo receptor and CRMP-2 phosphorylation. Brain : a journal of neurology 99 22544872
2008 Nogo-A and myelin-associated glycoprotein differently regulate oligodendrocyte maturation and myelin formation. The Journal of neuroscience : the official journal of the Society for Neuroscience 99 18632947
2003 Genomic structure and functional characterisation of the promoters of human and mouse nogo/rtn4. Journal of molecular biology 99 12488097
2003 Nogo-A expression in the intact and injured nervous system. Molecular and cellular neurosciences 97 14697671
2002 Nogo on the go. Neuron 89 12408839
2021 RTN4/NoGo-receptor binding to BAI adhesion-GPCRs regulates neuronal development. Cell 74 34758294
2005 Multiple signals regulate axon regeneration through the Nogo receptor complex. Molecular neurobiology 72 16215275
2003 HBO suppresses Nogo-A, Ng-R, or RhoA expression in the cerebral cortex after global ischemia. Biochemical and biophysical research communications 67 12951059
2010 Silencing Nogo-A promotes functional recovery in demyelinating disease. Annals of neurology 66 20437585
2006 Nogo-A expression in the human hippocampus in normal aging and in Alzheimer disease. Journal of neuropathology and experimental neurology 66 16772867
2004 Mutations of the Nogo-66 receptor (RTN4R) gene in schizophrenia. Human mutation 59 15532024
2003 Molecular analysis of Nogo expression in the hippocampus during development and following lesion and seizure. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 57 12692091
2014 Nogo-A: Multiple Roles in CNS Development, Maintenance, and Disease. The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry 55 24402613
2007 Targeting the Nogo-A signalling pathway to promote recovery following acute CNS injury. Current pharmaceutical design 55 17692015
2008 Novel roles for Nogo receptor in inflammation and disease. Trends in neurosciences 53 18394723
2007 Synaptic destabilization by neuronal Nogo-A. Brain cell biology 52 17957480
2010 Nogo-B receptor is essential for angiogenesis in zebrafish via Akt pathway. Blood 51 20813898
2002 Nogo and the Nogo-66 receptor. Progress in brain research 51 12440378
2019 mRNA levels can be reduced by antisense oligonucleotides via no-go decay pathway. Nucleic acids research 50 31165876
2008 Cell autonomous function of Nogo and reticulons: The emerging story at the endoplasmic reticulum. Journal of cellular physiology 50 18330888
2010 Genetic deletion of Nogo/Rtn4 ameliorates behavioral and neuropathological outcomes in amyloid precursor protein transgenic mice. Neuroscience 46 20433905
2017 Nogo-A antibodies enhance axonal repair and remyelination in neuro-inflammatory and demyelinating pathology. Acta neuropathologica 45 28646336
2003 Multi-functional gene ASY/Nogo/RTN-X/RTN4: apoptosis, tumor suppression, and inhibition of neuronal regeneration. Apoptosis : an international journal on programmed cell death 45 12510146
2018 RTN4 Knockdown Dysregulates the AKT Pathway, Destabilizes the Cytoskeleton, and Enhances Paclitaxel-Induced Cytotoxicity in Cancers. Molecular therapy : the journal of the American Society of Gene Therapy 43 30078441
2014 Cell type-specific Nogo-A gene ablation promotes axonal regeneration in the injured adult optic nerve. Cell death and differentiation 42 25257170
2004 Nogo and Nogo-66 receptor in human and chick: implications for development and regeneration. Developmental dynamics : an official publication of the American Association of Anatomists 41 15305291
2006 ER stress triggers apoptosis induced by Nogo-B/ASY overexpression. Experimental cell research 40 16687140
2005 Why do Nogo/Nogo-66 receptor gene knockouts result in inferior regeneration compared to treatment with neutralizing agents? Journal of neurochemistry 40 16092935
2022 RTN4/Nogo-A-S1PR2 negatively regulates angiogenesis and secondary neural repair through enhancing vascular autophagy in the thalamus after cerebral cortical infarction. Autophagy 39 35263212
2011 Neuronal Nogo-A regulates glutamate receptor subunit expression in hippocampal neurons. Journal of neurochemistry 38 21985178
2015 The Nogo/Nogo Receptor (NgR) Signal Is Involved in Neuroinflammation through the Regulation of Microglial Inflammatory Activation. The Journal of biological chemistry 37 26472924
2013 Nogo and Nogo receptor: relevance to schizophrenia? Neurobiology of disease 37 23369871
2004 Expression pattern of NOGO-A protein in the human nervous system. Acta neuropathologica 37 15616791
2003 Intraneuronal localization of Nogo-A in the rat. The Journal of comparative neurology 37 12577319
2003 Pro-apoptotic ASY/Nogo-B protein associates with ASYIP. Journal of cellular physiology 35 12811824
2016 Matrine Treatment Blocks NogoA-Induced Neural Inhibitory Signaling Pathway in Ongoing Experimental Autoimmune Encephalomyelitis. Molecular neurobiology 34 27933584
2017 Nogo-A Antibodies for Progressive Multiple Sclerosis. CNS drugs 32 28105588
2013 Multiple sclerosis: does Nogo play a role? The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry 32 23423307
2011 Interaction between amyloid precursor protein and Nogo receptors regulates amyloid deposition. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 32 21670066
2002 Nogos and the Nogo-66 receptor: factors inhibiting CNS neuron regeneration. Journal of neuroscience research 32 11891768
2012 The role of Nogo-A in neuroregeneration: a review. Brain research bulletin 30 22414960
2003 Nogo (Reticulon 4) expression in innervated and denervated mouse skeletal muscle. Molecular and cellular neurosciences 30 12691732
2025 Safety and efficacy of intrathecal antibodies to Nogo-A in patients with acute cervical spinal cord injury: a randomised, double-blind, multicentre, placebo-controlled, phase 2b trial. The Lancet. Neurology 29 39706632
2020 Evaluating the effectiveness of anti-Nogo treatment in spinal cord injuries. Neural development 29 31918754
2006 Expression of Nogo-A and NgR in the developing rat brain after hypoxia-ischemia. Brain research 29 16928363
2016 Nogo-C regulates cardiomyocyte apoptosis during mouse myocardial infarction. Cell death & disease 28 27763637
2012 The Nogo-66 receptor family in the intact and diseased CNS. Cell and tissue research 28 22311207
2021 A Novel Role of Nogo Proteins: Regulating Macrophages in Inflammatory Disease. Cellular and molecular neurobiology 27 34224050
2004 Identification of two NOGO/RTN4 genes and analysis of Nogo-A expression in Xenopus laevis. Molecular and cellular neurosciences 27 15019938
2023 Nogo-A reduces ceramide de novo biosynthesis to protect from heart failure. Cardiovascular research 26 35815623
2021 Nogo-A Is Critical for Pro-Inflammatory Gene Regulation in Myocytes and Macrophages. Cells 26 33572505
2017 Control of Cell Shape, Neurite Outgrowth, and Migration by a Nogo-A/HSPG Interaction. Developmental cell 26 28943240
2011 Anti-Nogo-A and training: can one plus one equal three? Experimental neurology 26 21530508
2007 The interaction of Nogo-66 receptor with Nogo-p4 inhibits the neuronal differentiation of neural stem cells. Neuroscience 26 18082332
2016 Nogo-A controls structural plasticity at dendritic spines by rapidly modulating actin dynamics. Hippocampus 25 26748478
2014 Maintaining stable memory engrams: new roles for Nogo-A in the CNS. Neuroscience 25 25168730
2014 Progesterone alters Nogo-A, GFAP and GAP-43 expression in a rat model of traumatic brain injury. Molecular medicine reports 24 24567055
2008 Localization of Nogo and its receptor in the optic pathway of mouse embryos. Journal of neuroscience research 24 18214994
2019 Extracellular Pgk1 enhances neurite outgrowth of motoneurons through Nogo66/NgR-independent targeting of NogoA. eLife 23 31361595
2009 Soluble Nogo receptor down-regulates expression of neuronal Nogo-A to enhance axonal regeneration. The Journal of biological chemistry 23 19901030
2005 Expression pattern of NOGO and NgR genes during human development. Gene expression patterns : GEP 23 15749087
2008 Nogo-Nogo receptor signalling in PNS axon outgrowth and pathfinding. Molecular and cellular neurosciences 22 19041397
2016 Nogo-A inhibits the migration and invasion of human malignant glioma U87MG cells. Oncology reports 21 27109183
2015 Function of Nogo-A/Nogo-A receptor in Alzheimer's disease. CNS neuroscience & therapeutics 21 25732725
2008 Nogo-a expression in glial CNS tumors: a tool to differentiate between oligodendrogliomas and other gliomas? The American journal of surgical pathology 21 18685489
2021 NogoA-expressing astrocytes limit peripheral macrophage infiltration after ischemic brain injury in primates. Nature communications 20 34824275
2017 Nogo-A in the visual system development and in ocular diseases. Biochimica et biophysica acta. Molecular basis of disease 20 28408340
2013 Expression pattern of Nogo-A, MAG, and NgR in regenerating urodele spinal cord. Developmental dynamics : an official publication of the American Association of Anatomists 20 23592243
2021 Modulation of Nogo receptor 1 expression orchestrates myelin-associated infiltration of glioblastoma. Brain : a journal of neurology 19 33479772
2018 Can We Design a Nogo Receptor-Dependent Cellular Therapy to Target MS? Cells 19 30577457
2015 Nogo-B protects mice against lipopolysaccharide-induced acute lung injury. Scientific reports 19 26174362
2008 Nogo-A and Nogo-66 receptor in amyotrophic lateral sclerosis. Journal of cellular and molecular medicine 19 18419791
2022 Nogo-B promotes invasion and metastasis of nasopharyngeal carcinoma via RhoA-SRF-MRTFA pathway. Cell death & disease 18 35075114
2022 Inhibition of Nogo-A rescues synaptic plasticity and associativity in APP/PS1 animal model of Alzheimer's disease. Seminars in cell & developmental biology 18 35431138
2021 Effect of Naoluoxintong on the NogoA/RhoA/ROCK pathway by down-regulating DNA methylation in MCAO rats. Journal of ethnopharmacology 18 34461189
2015 Nogo-A expression dynamically varies after spinal cord injury. Neural regeneration research 18 25883620
2014 Expression of Nogo isoforms and Nogo-B receptor (NgBR) in non-small cell lung carcinomas. Anticancer research 18 25075030
2011 Nogo-A expression in oligodendroglial tumors. Neuropathology : official journal of the Japanese Society of Neuropathology 18 20487307
2024 Endoplasmic reticulum morphology regulation by RTN4 modulates neuronal regeneration by curbing luminal transport. Cell reports 17 38955182
2023 Nogo-A and LINGO-1: Two Important Targets for Remyelination and Regeneration. International journal of molecular sciences 17 36901909
2018 Platelet procoagulant phenotype is modulated by a p38-MK2 axis that regulates RTN4/Nogo proximal to the endoplasmic reticulum: utility of pathway analysis. American journal of physiology. Cell physiology 17 29412690
2014 Essential roles of zebrafish rtn4/Nogo paralogues in embryonic development. Neural development 17 24755266

Missed literature

Know a paper Affinage missed for RTN4? Flag it for the maintainers and the community.

No submissions yet.