Affinage

RTN3

Reticulon-3 · UniProt O95197

Length
1032 aa
Mass
112.6 kDa
Annotated
2026-06-10
42 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RTN3 is an ER-resident reticulon protein that shapes tubular ER and acts as a multifunctional regulator of membrane dynamics, lipid metabolism, and cell-fate signaling (PMID:28617241, PMID:17699523). It adopts an omega-shaped membrane topology with two long transmembrane domains and cytosolically exposed N- and C-termini, a configuration whose integrity is required for its protein interactions (PMID:17699523). The full-length long isoform functions as a selective ER-phagy receptor: its oligomerization fragments ER tubules, and multiple N-terminal LIR motifs bind LC3s/GABARAPs to deliver tubular ER to lysosomes through conventional autophagy machinery independently of FAM134B (PMID:28617241). RTN3 is a direct negative regulator of the beta-secretase BACE1, binding it via the BACE1 transmembrane region, retaining it in the ER where APP cleavage is disfavored, and limiting amyloid-beta production; loss of RTN3 raises BACE1 levels and amyloid deposition in vivo while its overexpression reduces amyloid burden (PMID:16965550, PMID:25319692, PMID:19625507). RTN3 modulates lipid homeostasis through interactions with HSPA5/GRP78, FABP5, and DHCR7, influencing triglyceride and lipid-droplet biogenesis and cholesterol/EGFR signaling (PMID:29716941, PMID:38017147, PMID:41813657). It additionally restrains RIG-I antiviral signaling by impairing TRIM25-mediated K63-linked ubiquitination of RIG-I (PMID:34313226), and serves as an ER scaffold that recruits apoptotic machinery and partners including FADD/caspase-8 and Bcl-2 to tune cell survival and ER stress responses (PMID:17031492, PMID:17379544). A neuroprotective role downstream of cold-induced RBM3 has also been established in vivo (PMID:28238655).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 2005 Medium

    Established that RTN3 partners with another reticulon and resides in the ER, defining its baseline membrane localization and self-association behavior.

    Evidence Yeast two-hybrid, Co-IP, immunofluorescence co-localization with ASY/Nogo-B (RTN4) in human cells

    PMID:12811824

    Open questions at the time
    • Functional consequence of the RTN3-RTN4 complex not defined
    • ER retrieval motif role not tested for trafficking
  2. 2005 Medium

    Showed that excess RTN3 can drive ER-stress apoptosis, raising the question of how an ER-shaping protein controls cell fate.

    Evidence Overexpression in HeLa cells with Ca2+ flux, caspase-12 activation, and mitochondrial dysfunction readouts

    PMID:15799019

    Open questions at the time
    • Overexpression model may not reflect endogenous signaling
    • Direct effectors of the ER overload response not identified
  3. 2006 High

    Identified RTN3 as a direct binding partner and negative regulator of BACE1, linking it to amyloid-beta production.

    Evidence Reciprocal Co-IP in SH-SY5Y/HEK293, BACE1 ectodomain deletion mapping, Abeta secretion assay

    PMID:16965550

    Open questions at the time
    • Endogenous stoichiometry of the interaction unknown
    • Mechanism of activity inhibition vs. trafficking control not separated
  4. 2006 Medium

    Connected ER-bound RTN3 to extrinsic apoptotic signaling by showing it recruits FADD and triggers a caspase-8 cascade.

    Evidence Endogenous Co-IP, dominant-negative FADD epistasis, caspase-8/cytochrome c assays under tunicamycin

    PMID:17031492

    Open questions at the time
    • Single-lab finding without independent replication
    • How an ER-resident protein engages canonical death-receptor adaptors mechanistically unclear
  5. 2007 High

    Resolved the omega-shaped topology of RTN3 and tied it directly to BACE1 binding, providing the structural basis for its inhibitory function.

    Evidence Membrane topology mapping plus site-directed mutagenesis linked to BACE1 binding and activity

    PMID:17699523

    Open questions at the time
    • High-resolution structure not determined
    • Oligomerization geometry not defined
  6. 2007 Medium

    Extended RTN3's apoptotic role by showing it interacts with Bcl-2 and redistributes it, integrating pro- and anti-apoptotic balance at the ER.

    Evidence Co-IP, subcellular fractionation, Bcl-2 overexpression apoptosis assays in HeLa

    PMID:17379544

    Open questions at the time
    • Direct binding interface not mapped
    • Relationship to FADD-driven pathway unresolved
  7. 2009 High

    Demonstrated in vivo that RTN3 overexpression retains BACE1 in the ER and lowers amyloid burden, establishing trafficking control as a mechanism.

    Evidence RTN3 x APP/PS1 transgenic mice with amyloid quantification and BACE1 localization studies

    PMID:19625507

    Open questions at the time
    • Effect of RTN3 aggregates that offset inhibition not fully mechanistically dissected
  8. 2009 Medium

    Linked RTN3 to death-receptor sensitization by showing it upregulates DR5 and downregulates c-FLIP.

    Evidence Stable overexpression, DR5 siRNA and DR5/Fc blocking, TRAIL apoptosis assays

    PMID:19250737

    Open questions at the time
    • Transcriptional vs. post-translational basis of DR5 upregulation unknown
    • Single-lab overexpression study
  9. 2014 High

    Provided loss-of-function genetic proof that RTN3 negatively regulates BACE1 stability and amyloid deposition in vivo.

    Evidence RTN3-null mice and crosses to AD models with BACE1/APP processing biochemistry and histology

    PMID:25319692

    Open questions at the time
    • Molecular basis for BACE1 protein stabilization on RTN3 loss not defined
  10. 2017 High

    Defined RTN3 as a selective ER-phagy receptor, assigning it a distinct catabolic function within the reticulon family.

    Evidence Selective autophagy assays, LIR-motif mutagenesis, LC3 Co-IP, live imaging, FAM134B-KO epistasis

    PMID:28617241

    Open questions at the time
    • Signal triggering RTN3 oligomerization/activation unknown
    • Cargo selectivity determinants not fully mapped
  11. 2017 High

    Placed RTN3 downstream of cold-induced RBM3 as a translationally regulated neuroprotective effector.

    Evidence Translatome profiling, RBM3 RNA-binding assay, RTN3 knockdown and lentiviral overexpression in mouse neurodegeneration models

    PMID:28238655

    Open questions at the time
    • Molecular mechanism by which RTN3 prevents synaptic loss not resolved
    • Relation to ER-phagy or BACE1 functions unclear
  12. 2018 Medium

    Connected RTN3 to lipid metabolism through HSPA5 binding driving triglyceride biosynthesis and lipid-droplet expansion.

    Evidence RTN3 transgenic and null mice, HSPA5 Co-IP, SREBP-1c/AMPK assays, 3T3L1 and C. elegans models

    PMID:29716941

    Open questions at the time
    • Direct mechanistic step from HSPA5 binding to SREBP-1c activation not defined
    • Single-lab study
  13. 2018 Medium

    Identified BAP31 as a stabilizer of the RTN3 monomer, linking RTN3 aggregation state to BACE1-driven amyloid processing.

    Evidence Co-IP, conditional BAP31-KO mice crossed with APP/PS1, hippocampal neuron culture

    PMID:30596517

    Open questions at the time
    • Why monomer vs. aggregate differentially regulates BACE1 not mechanistically resolved
  14. 2018 Medium

    Linked an RTN3 coding variant and reduced expression to early-onset AD by impairing BACE1 axonal transport.

    Evidence Luciferase reporter for 5'-UTR variant and kymography of BACE1-RFP mobility in neurons

    PMID:29356939

    Open questions at the time
    • Pathogenicity of T39M not established beyond cell-based assays
    • No family co-segregation data in the timeline
  15. 2021 High

    Established RTN3 as a negative regulator of innate antiviral signaling by impairing TRIM25-mediated K63 ubiquitination of RIG-I.

    Evidence Co-IP with TRIM25 and RIG-I, K63-linked ubiquitination assay, IRF3/NF-kB reporters, VSV challenge in RTN3-overexpressing mice

    PMID:34313226

    Open questions at the time
    • How RTN3 aggregation sequesters the TRIM25/RIG-I complex structurally unclear
  16. 2022 Medium

    Showed RTN3 deficiency drives renal fibrosis via GPBP1 interaction and IGF2-JAK2-STAT3 activation.

    Evidence RTN3-null mice, GPBP1 Co-IP, pathway analysis in proximal tubular cells

    PMID:35596061

    Open questions at the time
    • Direct effect of RTN3 on GPBP1 function not defined
    • Single-lab finding
  17. 2023 Medium

    Extended RTN3's lipid role to cardiomyocytes by direct FABP5 binding driving fatty-acid delivery and DGAT2-dependent lipid-droplet biogenesis.

    Evidence RTN3-FABP5 Co-IP, gain/loss-of-function, DGAT2 inhibition, C/EBPalpha ChIP, HFD mice

    PMID:38017147

    Open questions at the time
    • Whether FABP5 transport mechanism generalizes beyond cardiomyocytes untested
  18. 2023 Medium

    Implicated RTN3-GRP78 interaction in hepatic mitochondrial dysfunction and steatosis via AMPK-IDH2 suppression.

    Evidence GRP78 Co-IP, AMPK/IDH2 assays, RTN3-null mice, hepatocyte/L02/C. elegans models

    PMID:36925557

    Open questions at the time
    • Relationship to the HSPA5-SREBP-1c lipid axis not reconciled
    • Single-lab study
  19. 2023 Medium

    Showed RTN3 (with RTN4) is co-opted by SARS-CoV-2 to build replication organelles via NSP3/NSP4 interaction.

    Evidence Interaction studies with viral NSP3/NSP4 and replication organelle formation assay (commentary citing primary study)

    PMID:37318453

    Open questions at the time
    • Entry is a commentary; primary mechanistic detail limited
    • Specific RTN3 contribution vs. RTN4 not separated
  20. 2024 Medium

    Defined an RTN3-HSPA9-VDAC2 complex at MAMs mediating ER-mitochondrion contact and protecting against kidney injury.

    Evidence Three-protein Co-IP, RTN3-null mice with cisplatin, MAM analysis in renal tubular cells

    PMID:38336146

    Open questions at the time
    • Stoichiometry and assembly order of the complex unknown
    • Single-lab study
  21. 2024 Medium

    Linked RTN3 aggregation to tau pathology by recruiting PP2A B subunits and suppressing PP2A activity in a feedforward cycle.

    Evidence Interactome analysis, social-isolation AD mouse model, PP2A activity and tau phosphorylation assays, senktide disruption

    PMID:38011644

    Open questions at the time
    • AI-assisted docking interactions not all biochemically validated
    • Trigger of presynaptic aggregation unresolved
  22. 2025 Medium

    Showed RTN3 controls CRTH2 levels differentially across cell types to restrain pulmonary fibrosis.

    Evidence RTN3-CRTH2 Co-IP, RTN3-null mice with bleomycin, fibroblast and macrophage studies, autophagy assays

    PMID:39972424

    Open questions at the time
    • Mechanism of cell-type-specific CRTH2 regulation not fully defined
    • Single-lab study
  23. 2026 Medium

    Identified RTN3 as a promoter of DHCR7 ubiquitination, linking RTN3 loss to cholesterol-driven EGFR/ERK activation in cancer.

    Evidence RTN3-DHCR7 Co-IP, ubiquitination assay, EGFR/ERK pathway assays, simvastatin rescue

    PMID:41813657

    Open questions at the time
    • Whether RTN3 itself is or recruits the E3 ligase unclear
    • Single-lab study

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RTN3's many context-specific functions — ER-phagy, BACE1 regulation, lipid metabolism, antiviral signaling, and apoptosis — are coordinated by its oligomerization/aggregation state and topology in a single cell remains unresolved.
  • No unifying model linking monomer/aggregate state to the distinct downstream pathways
  • No high-resolution structure of RTN3 or its complexes
  • Signals that switch RTN3 between functions not identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2 GO:0008289 lipid binding 2 GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005783 endoplasmic reticulum 3 GO:0005739 mitochondrion 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-1643685 Disease 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-392499 Metabolism of proteins 2 R-HSA-168256 Immune System 1 R-HSA-9612973 Autophagy 1
Partners
BACE1BAP31BCL-2DHCR7FABP5FADDHSPA5TRIM25
Complex memberships
RTN3-HSPA9-VDAC2 MAM complexRTN3-RTN4 (Nogo-B) reticulon complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2017 Full-length RTN3 (long isoform) acts as a selective autophagy receptor for ER-phagy of tubular ER. Oligomerization of the long isoform is sufficient to trigger fragmentation of ER tubules. The long N-terminal region of RTN3 contains multiple LC3-interacting regions (LIR motifs), and binding to LC3s/GABARAPs is essential for tubule fragmentation and lysosomal delivery. RTN3-mediated ER-phagy requires conventional autophagy components but is independent of FAM134B. Selective autophagy assays, LC3 co-immunoprecipitation, LIR motif identification/mutagenesis, live imaging, lysosomal delivery assays, genetic epistasis with FAM134B KO eLife High 28617241
2006 RTN3 physically interacts with BACE1 via the transmembrane region of BACE1, and overexpression of RTN3 inhibits BACE1 activity, reducing Abeta40 and Abeta42 secretion by 30–50%. RTN3 also interacts with BACE2. Co-immunoprecipitation in SH-SY5Y and HEK293 cells, proteomic identification, BACE1 ectodomain deletion mutant binding assay, Abeta secretion assay The European journal of neuroscience High 16965550
2007 RTN3 adopts an omega-shaped membrane topology with two long transmembrane domains and both N- and C-termini facing the cytosolic side. The first transmembrane domain dictates membrane integration. Subtle alterations in this topology disrupt RTN3 binding to BACE1 and abolish its inhibitory effects on BACE1 activity. Membrane topology mapping assays, site-directed mutagenesis, co-immunoprecipitation, BACE1 activity assay The Journal of biological chemistry High 17699523
2014 RTN3 deficiency in mice increases BACE1 protein levels and enhances APP processing at the beta-secretase site, leading to increased amyloid deposition in Alzheimer's mouse models. This demonstrates RTN3 negatively regulates BACE1 protein stability and activity in vivo. RTN3-null mouse generation, biochemical analysis of BACE1 levels and APP processing, histological analysis of amyloid deposition in RTN3-null x AD model mice The Journal of neuroscience High 25319692
2009 RTN3 overexpression reduces amyloid deposition in cortex and hippocampus of APP/PS1 mice, and this is associated with retention of BACE1 in the ER compartment where APP cleavage is less favored, altering BACE1 intracellular trafficking. RTN3 aggregates in dystrophic neurites offset this inhibitory effect. Triple transgenic mouse model (RTN3 overexpressor x APP/PS1), amyloid burden quantification, BACE1 intracellular localization studies, immunohistochemistry The Journal of neuroscience High 19625507
2005 RTN3 (identified as ASYIP) forms a complex with ASY/Nogo-B (RTN4) in human cells; both hydrophobic transmembrane regions of RTN3 are required for this association. RTN3 co-localizes with ASY/Nogo-B in the ER, as shown by immunofluorescence. RTN3 contains a double-lysine ER retrieval motif at its C-terminus. Yeast two-hybrid cloning, co-immunoprecipitation in human cells, immunofluorescence co-localization, deletion/mutational analysis Journal of cellular physiology Medium 12811824
2005 RTN3 overexpression triggers ER overload response (EOR)-induced apoptosis through depletion of ER Ca2+ stores and sustained elevation of cytosolic Ca2+, activating caspase-12 and mitochondrial dysfunction. Overexpressed RTN3 also induces iNOS upregulation via Ca2+ release and reactive oxygen intermediates as a protective feedback. Overexpression in HeLa cells, Ca2+ measurement, caspase-12 activation assay, mitochondrial dysfunction assay, iNOS reporter/Western blot Journal of cellular physiology Medium 15799019
2006 Endogenous FADD is recruited by ER-bound RTN3 to the ER membrane, initiating caspase-8 cascade including Bid processing and cytochrome c release from mitochondria. Dominant-negative FADD (DD domain) abolishes these RTN3-mediated caspase-8 cascade events. Endogenous FADD is also recruited by endogenous RTN3 upon tunicamycin stimulation. Co-immunoprecipitation of endogenous proteins, dominant-negative FADD overexpression, caspase-8 activation assay, cytochrome c release assay, tunicamycin stimulation Apoptosis Medium 17031492
2007 RTN3 interacts with Bcl-2 on the ER membrane. Overexpressed Bcl-2 reduces RTN3-induced apoptosis. Increased endogenous RTN3 in the microsomal fraction (upon tunicamycin) enhances Bcl-2 localization to both microsomal and mitochondrial fractions, potentiating Bcl-2 anti-apoptotic activity. Co-immunoprecipitation, subcellular fractionation, apoptosis assay, Bcl-2 stable overexpression in HeLa cells Cell biology international Medium 17379544
2009 RTN3 overexpression upregulates death receptor DR5 surface protein and downregulates c-FLIP, sensitizing cells to TRAIL-mediated apoptosis. DR5 siRNA or DR5/Fc chimera blocks RTN3-mediated TRAIL sensitization, establishing DR5 as the primary mediator. RTN3 also enhances TNF-alpha and Fas-mediated apoptosis. Stable RTN3 overexpression, DR5 siRNA knockdown, DR5/Fc chimera blocking, flow cytometry for DR4/DR5 surface levels, TRAIL apoptosis assay, c-FLIP Western blot Cancer letters Medium 19250737
2009 RTN3 (CRELD1 binding partner) is recruited by CRELD1 interaction, which shifts RTN3 localization from the ER to the plasma membrane and moderately decreases RTN3-mediated apoptotic activity. CRELD1 interaction also partially suppresses tunicamycin-induced apoptosis. Co-immunoprecipitation of ectopic and endogenous RTN3 with CRELD1, immunofluorescence localization, apoptosis assay Molecular and cellular biochemistry Low 19521671
2017 RTN3 expression is induced by cold/hypothermia and is a downstream effector of RBM3-mediated neuroprotection. RBM3 binds to RTN3 mRNA to drive increased RTN3 translation. RTN3 knockdown in mice eliminates cooling-induced neuroprotection; lentiviral RTN3 overexpression independently prevents synaptic loss and cognitive deficits in a mouse neurodegeneration model downstream of RBM3. Translatome profiling, RBM3 RNA-binding assay, RTN3 knockdown in mice (lentiviral), lentiviral RTN3 overexpression in mouse neurodegeneration model, cognitive/synaptic phenotyping Current biology High 28238655
2018 RTN3 interacts with HSPA5 (GRP78/BiP), and this interaction increases SREBP-1c and AMPK activity, promoting triglyceride biosynthesis and lipid droplet expansion. RTN3 transgenic mice develop obesity and hypertriglyceridemia; RTN3-null mice have reduced triglyceride accumulation. RTN3 transgenic and null mouse models, co-immunoprecipitation with HSPA5, SREBP-1c and AMPK activity assays, 3T3L1 cell culture, C. elegans genetic models Circulation Medium 29716941
2018 BAP31 is a binding partner of RTN3 that stabilizes RTN3 monomer. BAP31 knockout in hippocampal neurons decreases RTN3 monomer availability, increases RTN3 aggregates, and consequently enhances BACE1-mediated APP processing and amyloid plaque formation. Co-immunoprecipitation of BAP31 and RTN3, conditional BAP31-KO mouse crossed with APP/PS1 AD model, primary hippocampal neuron culture, Western blot for RTN3 aggregates and BACE1 processing FASEB journal Medium 30596517
2021 RTN3 is upregulated during RNA viral infection and acts as a negative regulator of RIG-I antiviral signaling. RTN3 aggregates on the ER and interacts with both TRIM25 and RIG-I, impairing K63-linked polyubiquitination of RIG-I, resulting in inhibition of IRF3 and NF-κB activation. RTN3 overexpression in mice reduces neutrophil infiltration and inflammatory damage upon VSV challenge. Co-immunoprecipitation of RTN3 with TRIM25 and RIG-I, ubiquitination assay (K63-linked), IRF3/NF-κB reporter assay, RTN3-overexpressing mouse model challenged with VSV, immunohistochemistry eLife High 34313226
2022 RTN3 deficiency in kidney proximal tubular epithelial cells activates the IGF2-JAK2-STAT3 pathway through interaction with GPBP1, leading to collagen biosynthesis upregulation and mitochondrial dysfunction, phenocopying chronic kidney disease and fibrosis. RTN3-null mouse model, co-immunoprecipitation with GPBP1, IGF2-JAK2-STAT3 pathway analysis, primary proximal tubular epithelial cells, HEK293 cells in vitro Experimental & molecular medicine Medium 35596061
2023 RTN3 directly binds FABP5 to facilitate directed transport of fatty acids to the ER, promoting lipid droplet biogenesis in a DGAT2-dependent manner in cardiomyocytes. Lipid overload-induced RTN3 upregulation is driven by C/EBPα, which binds the RTN3 promoter. Co-immunoprecipitation of RTN3 and FABP5, gain/loss-of-function in cardiomyocytes, DGAT2 inhibition, C/EBPα promoter binding assay (ChIP), HFD mouse model Cell death and differentiation Medium 38017147
2023 RTN3 interacts with GRP78 (HSPA5) in hepatocytes, and increased RTN3 inhibits the AMPK-IDH2 pathway, leading to mitochondrial dysfunction and lipid accumulation phenocopying NAFLD. RTN3 knockout relieves fatty liver and mitochondrial dysfunction. Co-immunoprecipitation with GRP78, AMPK and IDH2 activity assays, RTN3-null mouse model, primary hepatocytes, L02 cell line, C. elegans strain, HFD model MedComm Medium 36925557
2024 RTN3 deficiency disrupts the RTN3-HSPA9-VDAC2 complex at mitochondria-associated membranes (MAMs), impairing ER-mitochondrion contact and causing mitochondrial dysfunction that exacerbates cisplatin-induced acute kidney injury. Co-immunoprecipitation of RTN3, HSPA9, and VDAC2, RTN3-null mouse model with cisplatin treatment, primary renal tubular epithelial cells, HK2 cell line, MAM analysis Mitochondrion Medium 38336146
2024 In socially isolated AD mice, RTN3 aggregates in presynaptic regions and disturbs mossy fibre bouton formation by recruiting multiple mitochondrial and vesicle-related proteins. RTN3 aggregation also recruits PP2A B subunits, suppressing PP2A activity and inducing tau hyperphosphorylation, which further elevates RTN3 in a feedforward cycle. RTN3 interactome analysis (AI-assisted molecular docking), in vivo mouse model (social isolation + AD), PP2A activity assay, tau phosphorylation analysis, senktide treatment to disrupt RTN3 interactions Protein & cell Medium 38011644
2025 RTN3 interacts with CRTH2 in lung fibroblasts; RTN3 deficiency reduces ER-anchored CRTH2 (which antagonizes collagen biosynthesis) and simultaneously reduces autophagy-mediated degradation of CRTH2 in macrophages (where CRTH2 activates profibrotic differentiation), resulting in aggravated pulmonary fibrosis. Co-immunoprecipitation of RTN3 and CRTH2, RTN3-null mouse model with bleomycin treatment, lung fibroblast and alveolar macrophage studies, autophagy assay Molecular medicine Medium 39972424
2011 RTN3 interacts with Ras at the ER, as demonstrated by confocal co-localization and co-immunoprecipitation. RTN3 upregulation during HSV mutant infection correlates with decreased Ras on the plasma membrane. Confocal co-localization, co-immunoprecipitation, siRNA knockdown of RTN3, Western blot and flow cytometry for Ras distribution Cancer biology & therapy Low 17218780
2026 RTN3 directly interacts with DHCR7 and promotes its ubiquitination. RTN3 downregulation stabilizes DHCR7, elevating cholesterol concentration and activating the EGFR/ERK pathway in thyroid cancer. Co-immunoprecipitation of RTN3 and DHCR7, ubiquitination assay, RTN3 loss-of-function experiments, EGFR/ERK pathway activity assay, Simvastatin rescue Cell death & disease Medium 41813657
2023 RTN3 and RTN4 are required for the formation of SARS-CoV-2 replication organelles through direct interaction with viral proteins NSP3 and NSP4. Co-immunoprecipitation/interaction studies with viral NSP3/NSP4, RTN3/RTN4 loss-of-function, replication organelle formation assay (as described by Williams et al., cited in this commentary) The Journal of cell biology Medium 37318453
2018 RTN3 variant T39M (c.116C>T) found in early-onset AD patients causes impaired axonal transport of BACE1 when overexpressed in cultured neurons. The c.-8G>T 5'-UTR variant reduces RTN3 expression. Luciferase reporter assay for expression, kymograph analysis of BACE1-RFP particle mobility in neurons transfected with WT or variant RTN3 Human genetics Medium 29356939

Source papers

Stage 0 corpus · 42 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 Full length RTN3 regulates turnover of tubular endoplasmic reticulum via selective autophagy. eLife 368 28617241
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
1999 Cloning of a novel member of the reticulon gene family (RTN3): gene structure and chromosomal localization to 11q13. Genomics 71 10331947
2017 RTN3 Is a Novel Cold-Induced Protein and Mediates Neuroprotective Effects of RBM3. Current biology : CB 64 28238655
2014 Impact of RTN3 deficiency on expression of BACE1 and amyloid deposition. The Journal of neuroscience : the official journal of the Society for Neuroscience 53 25319692
2009 Reduced amyloid deposition in mice overexpressing RTN3 is adversely affected by preformed dystrophic neurites. The Journal of neuroscience : the official journal of the Society for Neuroscience 53 19625507
2005 ER Ca2+ depletion triggers apoptotic signals for endoplasmic reticulum (ER) overload response induced by overexpressed reticulon 3 (RTN3/HAP). Journal of cellular physiology 53 15799019
2024 Hypoxic tumor-derived exosomal miR-4488 induces macrophage M2 polarization to promote liver metastasis of pancreatic neuroendocrine neoplasm through RTN3/FABP5 mediated fatty acid oxidation. International journal of biological sciences 38 38904015
2007 The membrane topology of RTN3 and its effect on binding of RTN3 to BACE1. The Journal of biological chemistry 37 17699523
2018 Identification of rare RTN3 variants in Alzheimer's disease in Han Chinese. Human genetics 36 29356939
2017 RTN1 and RTN3 protein are differentially associated with senile plaques in Alzheimer's brains. Scientific reports 36 28733667
2003 Pro-apoptotic ASY/Nogo-B protein associates with ASYIP. Journal of cellular physiology 35 12811824
2018 Increased Reticulon 3 (RTN3) Leads to Obesity and Hypertriglyceridemia by Interacting With Heat Shock Protein Family A (Hsp70) Member 5 (HSPA5). Circulation 33 29716941
2018 BAP31 deficiency contributes to the formation of amyloid-β plaques in Alzheimer's disease by reducing the stability of RTN3. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 32 30596517
2017 Effects of altered RTN3 expression on BACE1 activity and Alzheimer's neuritic plaques. Reviews in the neurosciences 22 27883331
2009 Over-expression of Reticulon 3 (RTN3) enhances TRAIL-mediated apoptosis via up-regulation of death receptor 5 (DR5) and down-regulation of c-FLIP. Cancer letters 22 19250737
2023 Increased RTN3 phenocopies nonalcoholic fatty liver disease by inhibiting the AMPK-IDH2 pathway. MedComm 21 36925557
2007 Anti-apoptotic activity of Bcl-2 is enhanced by its interaction with RTN3. Cell biology international 20 17379544
2023 Lipid overload-induced RTN3 activation leads to cardiac dysfunction by promoting lipid droplet biogenesis. Cell death and differentiation 19 38017147
2021 LINC02288 promotes chondrocyte apoptosis and inflammation through miR-374a-3p targeting RTN3. The journal of gene medicine 19 33491257
2009 RTN3 inducing apoptosis is modulated by an adhesion protein CRELD1. Molecular and cellular biochemistry 15 19521671
2005 Identification of a new RTN3 transcript, RTN3-A1, and its distribution in adult mouse brain. Brain research. Molecular brain research 15 15946766
2013 Nogo/RTN4 isoforms and RTN3 expression protect SH-SY5Y cells against multiple death insults. Molecular and cellular biochemistry 14 23955438
2022 Loss of RTN3 phenocopies chronic kidney disease and results in activation of the IGF2-JAK2 pathway in proximal tubular epithelial cells. Experimental & molecular medicine 13 35596061
2021 RTN3 inhibits RIG-I-mediated antiviral responses by impairing TRIM25-mediated K63-linked polyubiquitination. eLife 13 34313226
2010 RTN3 and RTN4: Candidate modulators in vascular cell apoptosis and atherosclerosis. Journal of cellular biochemistry 12 20717916
2006 Adaptor FADD is recruited by RTN3/HAP in ER-bound signaling complexes. Apoptosis : an international journal on programmed cell death 12 17031492
2024 Senktide blocks aberrant RTN3 interactome to retard memory decline and tau pathology in social isolated Alzheimer's disease mice. Protein & cell 11 38011644
2022 Long noncoding RNA Kcnq1ot1 prompts lipopolysaccharide-induced acute lung injury by microRNA-7a-5p/Rtn3 axis. European journal of medical research 7 35317842
2007 Selectively oncolytic mutant of HSV-1 lyses HeLa cells mediated by Ras/RTN3. Cancer biology & therapy 7 17218780
2023 RTN3 and RTN4: Architects of SARS-CoV-2 replication organelles. The Journal of cell biology 6 37318453
2022 Circ_0043947 contributes to interleukin 1β-induced injury in chondrocytes by sponging miR-671-5p to up-regulate RTN3 expression in osteoarthritis pathology. Journal of orthopaedic surgery and research 6 35331286
2009 Variation in RTN3 and PPIL2 genes does not influence platelet membrane beta-secretase activity or susceptibility to alzheimer's disease in the northern Irish population. Neuromolecular medicine 6 19669607
2024 RTN3 deficiency exacerbates cisplatin-induced acute kidney injury through the disruption of mitochondrial stability. Mitochondrion 5 38336146
2014 mRNA levels of BACE1 and its interacting proteins, RTN3 and PPIL2, correlate in human post mortem brain tissue. Neuroscience 4 24853053
2024 Downregulating miR-432-5p exacerbates adriamycin-induced cardiotoxicity via activating the RTN3 signaling pathway. Aging 3 39177670
2015 [Molecular Mechanism of Action of hnRNP K and RTN3 in the Replication of Enterovirus 71]. Bing du xue bao = Chinese journal of virology 3 26164948
2025 RTN3 regulates collagen biosynthesis and profibrotic macrophage differentiation to promote pulmonary fibrosis via interacting with CRTH2. Molecular medicine (Cambridge, Mass.) 1 39972424
2026 Declined RTN3 stabilizes DHCR7 to induce cholesterol-dependent tumor progression and MEK inhibitors insensitivity in thyroid cancer. Cell death & disease 0 41813657
2026 Citrulline Modulates Milk Fat Metabolism via the RTN3-FABP5 Axis in Bovine Mammary Epithelial Cells. Journal of agricultural and food chemistry 0 41889269
2026 Beyond Free Virions: Interconnected Secretory Pathways and Reticulon 3 (RTN3) Coordinate Extracellular Vesicle Diversity for Infectious Exosome Generation. Biology 0 42117840
2024 Correction to: Increased RTN3 phenocopies nonalcoholic fatty liver disease by inhibiting the AMPK-IDH2 pathway. MedComm 0 38318159

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