Affinage

RTN3

Reticulon-3 · UniProt O95197

Length
1032 aa
Mass
112.6 kDa
Annotated
2026-04-28
100 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RTN3 is an ER-resident reticulon family protein that functions as a membrane-shaping scaffold, selective autophagy receptor, and signaling platform linking ER homeostasis to neurodegeneration, lipid metabolism, apoptosis, and innate immunity. RTN3 adopts an omega-shaped topology with both termini facing the cytosol; its long isoform oligomerizes via multiple LIR motifs to engage LC3/GABARAP and drive selective ER-phagy of tubular ER independently of the ER-sheet receptor FAM134B (PMID:28617241), while its short isoform retains BACE1 in the ER, reducing amyloidogenic APP processing in vivo—a function confirmed by both overexpression and knockout mouse models (PMID:19625507, PMID:25319692). Through its cytosolic N-terminal domain, RTN3 recruits diverse partners including FADD to initiate caspase-8-dependent apoptosis (PMID:17031492), TRIM25/RIG-I to suppress K63-linked ubiquitination and dampen antiviral interferon signaling (PMID:34313226), and HSPA5/GRP78 and FABP5 to modulate triglyceride biosynthesis, lipid droplet biogenesis, and mitochondrial function in metabolic tissues (PMID:29716941, PMID:38017147). Rare RTN3 coding and regulatory variants identified in Alzheimer's disease patients reduce RTN3 expression or impair axonal BACE1 transport, implicating RTN3 dysfunction in neurodegeneration (PMID:29356939).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1999 Medium

    Identification of RTN3 as a new reticulon family member established its genomic organization and broad tissue expression, with enrichment in brain, opening investigation into its neuronal and ER-related functions.

    Evidence Subtraction cloning, Southern/Northern blot, and somatic cell hybrid mapping in human tissues

    PMID:10331947

    Open questions at the time
    • No protein-level function assigned
    • No subcellular localization determined
    • No disease relevance established
  2. 2002 Medium

    Demonstrating that RTN3 localizes exclusively to the ER and that its overexpression depletes ER Ca²⁺ stores to trigger caspase-3-dependent apoptosis established a link between reticulon proteins and ER stress-induced cell death.

    Evidence Immunofluorescence, Ca²⁺ imaging, and caspase activity assays in HeLa cells

    PMID:12372622

    Open questions at the time
    • Mechanism of Ca²⁺ store depletion unclear
    • Relevance of overexpression-level apoptosis to endogenous physiology uncertain
  3. 2005 Medium

    Defining RTN3-induced ER overload response as a pathway distinct from the UPR—involving ER Ca²⁺ depletion, caspase-12 activation, mitochondrial dysfunction, and iNOS upregulation—clarified the specific stress signaling axis engaged by RTN3.

    Evidence Ca²⁺ imaging, caspase-12 activity, mitochondrial membrane potential, and iNOS assays in HeLa overexpression system

    PMID:15799019

    Open questions at the time
    • Endogenous RTN3 contribution to EOR not tested
    • No loss-of-function data
  4. 2006 Medium

    Showing that RTN3 recruits FADD to the ER to activate caspase-8 and downstream Bid/cytochrome c release provided a molecular mechanism for RTN3-initiated apoptosis, positioning RTN3 as an ER-localized platform for death receptor adaptor signaling.

    Evidence Co-immunoprecipitation, subcellular fractionation, and dominant-negative FADD rescue experiments

    PMID:17031492

    Open questions at the time
    • Direct binding vs. indirect complex not resolved
    • Physiological triggers for RTN3-FADD engagement not identified
  5. 2007 High

    Establishing RTN3's omega-shaped membrane topology and showing that topology perturbation abolishes BACE1 binding and inhibition revealed the structural basis for RTN3-mediated BACE1 regulation.

    Evidence Protease protection, glycosylation insertion topology mapping, mutagenesis, and BACE1 activity assays

    PMID:17699523

    Open questions at the time
    • No high-resolution structure of the RTN3-BACE1 interface
    • In vivo topology confirmation lacking
  6. 2009 High

    In vivo demonstration that RTN3 overexpression reduces amyloid deposition by retaining BACE1 in the ER—but that RTN3 aggregates in dystrophic neurites offset this benefit—connected RTN3 biology to Alzheimer's disease pathogenesis.

    Evidence Transgenic APP/PS1 × RTN3-overexpressing mouse cross with immunohistochemistry and BACE1 activity assays

    PMID:19625507

    Open questions at the time
    • Mechanism of RTN3 aggregate formation not defined
    • Aggregate-to-monomer balance regulation unknown
  7. 2014 High

    RTN3-null mice confirmed a non-redundant in vivo role: RTN3 loss elevates BACE1 protein and enhances amyloidogenic APP processing, providing definitive loss-of-function evidence complementing prior gain-of-function studies.

    Evidence RTN3-knockout mice crossed with AD models, Western blot, and amyloid plaque quantification

    PMID:25319692

    Open questions at the time
    • Whether RTN3 regulates BACE1 transcription, translation, or degradation was not fully resolved
    • Cognitive phenotype of RTN3-null mice not reported here
  8. 2017 High

    Discovery that the long RTN3 isoform is a selective ER-phagy receptor—oligomerizing and engaging LC3/GABARAP via multiple LIR motifs to deliver fragmented ER tubules to lysosomes—established a fundamentally new function for reticulon proteins in organelle quality control.

    Evidence Super-resolution live-cell imaging, LIR mutagenesis, autophagy flux assays, and siRNA in starvation-induced ER-phagy

    PMID:28617241

    Open questions at the time
    • Signals triggering RTN3 oligomerization in vivo not identified
    • Cargo selectivity determinants beyond ER tubule morphology unknown
    • Interplay with other ER-phagy receptors beyond FAM134B not explored
  9. 2017 High

    Identification of RTN3 as a cold-induced neuroprotective protein whose translation is maintained during hypothermia via RBM3 binding revealed a translational regulatory mechanism and demonstrated RTN3 sufficiency for synapse protection in a neurodegeneration model.

    Evidence Ribosome profiling, RNA immunoprecipitation, lentiviral overexpression and knockdown, mouse behavioral and synapse assays

    PMID:28238655

    Open questions at the time
    • Whether neuroprotection requires ER-phagy, BACE1 regulation, or another RTN3 function is unresolved
    • RBM3 binding site on RTN3 mRNA not mapped
  10. 2018 Medium

    Functional characterization of AD-associated RTN3 variants (c.-8G>T reducing expression, T39M impairing BACE1 axonal transport) provided human genetic evidence linking RTN3 dysfunction to Alzheimer's disease susceptibility.

    Evidence Luciferase reporter assay for UTR variant and kymograph analysis of BACE1-RFP transport in neurons

    PMID:29356939

    Open questions at the time
    • Variants identified in small cohort; genome-wide significance not demonstrated
    • Structural basis for T39M transport impairment unknown
  11. 2018 Medium

    RTN3 interaction with HSPA5/GRP78 was shown to drive triglyceride biosynthesis via SREBP1c and AMPK, causing obesity and hypertriglyceridemia in transgenic mice, extending RTN3 function beyond neurodegeneration into systemic metabolic regulation.

    Evidence RTN3 transgenic and null mice, 3T3-L1 cell culture, co-IP of RTN3-HSPA5, C. elegans models

    PMID:29716941

    Open questions at the time
    • Direct vs. indirect nature of RTN3-HSPA5 interaction not fully resolved
    • Whether ER-phagy and metabolic functions are linked or independent is unclear
  12. 2021 High

    RTN3 was established as a negative regulator of innate antiviral immunity by showing it aggregates on the ER during viral infection, binds TRIM25 and RIG-I, and impairs K63-linked polyubiquitination of RIG-I, suppressing IRF3/NF-κB signaling.

    Evidence Reciprocal co-IPs, K63-ubiquitination assays, reporter assays, RTN3-overexpressing mice challenged with VSV

    PMID:34313226

    Open questions at the time
    • Whether RTN3 aggregation state directly controls immunosuppressive function is not resolved
    • Relevance to non-RNA viral infections untested
  13. 2023 Medium

    RTN3 was shown to directly bind FABP5 to shuttle fatty acids to the ER for DGAT2-mediated lipid droplet biogenesis in the heart, with C/EBPα driving RTN3 transcription, revealing a tissue-specific lipid transport and storage mechanism.

    Evidence Co-IP of RTN3-FABP5, cardiac gain/loss-of-function mouse models, DGAT2 inhibitor rescue, promoter binding assays

    PMID:38017147

    Open questions at the time
    • Structural basis of RTN3-FABP5 interaction unknown
    • Whether FABP5 interaction occurs via the same domain as other partners not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RTN3's multiple functions—ER-phagy, BACE1 regulation, apoptosis, antiviral signaling, and lipid metabolism—are coordinately regulated across tissues and isoforms, and whether a unifying mechanism such as oligomerization state governs functional switching, remains unresolved.
  • No structural model of full-length RTN3 or its oligomeric assemblies
  • Signals controlling isoform-specific expression in different tissues not defined
  • Whether ER-phagy and BACE1-regulatory functions are mutually exclusive or synergistic is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 6 GO:0098772 molecular function regulator activity 3 GO:0008289 lipid binding 2
Localization
GO:0005783 endoplasmic reticulum 5 GO:0005811 lipid droplet 3
Pathway
R-HSA-5357801 Programmed Cell Death 4 R-HSA-1430728 Metabolism 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 1 R-HSA-9612973 Autophagy 1
Partners
BACE1BAP31FABP5FADDHSPA5NOGO-BRIG-ITRIM25

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 RTN3 was cloned and identified as a novel member of the reticulon (RTN) gene family, containing seven exons, spanning >15 kb, localized to chromosome 11q13, and widely expressed in human tissues with highest expression in brain. Subtraction cloning, Southern blot, Northern blot, somatic cell hybrid panel mapping Genomics Medium 10331947
2002 RTN3 (also called HAP) localizes exclusively to the endoplasmic reticulum and its overexpression induces apoptosis via depletion of ER Ca2+ stores, with caspase-3 activation. Immunofluorescence, Ca2+ imaging, caspase activity assay, overexpression in HeLa cells FEBS letters Medium 12372622
2002 RTN3/HAP generates two major mRNA transcripts (1.8 kb and 2.7 kb) via alternative polyadenylation; the 3'-UTR between the second and third polyadenylation signals exerts a translational activation function (~3-fold increase) without altering mRNA stability. Northern blot, alternative polyadenylation site mapping, reporter gene (CAT) assay, mRNA stability analysis Archives of biochemistry and biophysics Medium 12054434
2003 RTN3 (ASYIP) interacts with ASY/Nogo-B and both hydrophobic regions of RTN3 are required for this association; the complex co-localizes in the ER. Yeast two-hybrid, co-immunoprecipitation in human cells, mutational analysis, immunofluorescence Journal of cellular physiology Medium 12811824
2005 RTN3 overexpression triggers ER overload response (EOR) by depleting ER Ca2+ stores, elevating cytosolic Ca2+, activating caspase-12, causing mitochondrial dysfunction, and upregulating iNOS through reactive oxygen intermediates; this pathway is distinct from the UPR pathway. Ca2+ imaging, caspase activity assays, iNOS measurement, mitochondrial membrane potential assay, overexpression in HeLa cells Journal of cellular physiology Medium 15799019
2006 RTN3 recruits the adaptor protein FADD to the ER membrane, initiating a caspase-8 cascade (including Bid processing and cytochrome c release from mitochondria); dominant-negative FADD abolishes these RTN3-generated apoptotic events. Co-immunoprecipitation, subcellular fractionation, caspase-8 activity assay, cytochrome c release assay, dominant-negative FADD expression Apoptosis Medium 17031492
2007 RTN3 adopts an omega-shaped membrane topology with two long transmembrane domains and both N- and C-termini facing the cytosol; subtle changes in this topology disrupt RTN3 binding to BACE1 and abolish its inhibitory effects on BACE1 activity. Protease protection assay, glycosylation site insertion topology mapping, site-directed mutagenesis, BACE1 activity assay, co-immunoprecipitation The Journal of biological chemistry High 17699523
2007 RTN3 interacts with Bcl-2 at the ER; this interaction promotes Bcl-2 accumulation in mitochondrial fractions and enhances Bcl-2 anti-apoptotic activity; endogenous RTN3 increases in the microsomal fraction upon tunicamycin treatment, driving Bcl-2 redistribution. Co-immunoprecipitation, subcellular fractionation, overexpression/stable expression, apoptosis assay Cell biology international Medium 17379544
2009 RTN3 overexpression negatively modulates BACE1 activity by retaining more BACE1 in the ER compartment (where APP cleavage is less favored), thereby reducing amyloid deposition in vivo; however, preformed RTN3 aggregates in dystrophic neurites offset this inhibitory effect. Transgenic mouse cross (APP/PS1 × RTN3 overexpressing), immunohistochemistry, BACE1 activity assay, amyloid plaque quantification The Journal of neuroscience High 19625507
2009 RTN3 overexpression enhances TRAIL-mediated apoptosis by upregulating DR5 surface protein levels and downregulating c-FLIP; DR5 siRNA or DR5/Fc chimera blocked RTN3-mediated sensitization, placing DR5 downstream of RTN3. Overexpression in Caki cells, flow cytometry for surface DR5, siRNA knockdown, apoptosis assay, caspase inhibitor rescue Cancer letters Medium 19250737
2009 RTN3 interacts with CRELD1; this interaction increases RTN3 localization on the plasma membrane, decreases its ER localization, and moderately reduces RTN3-induced apoptosis. Co-immunoprecipitation, immunofluorescence, apoptosis assay Molecular and cellular biochemistry Low 19521671
2014 RTN3 deficiency in null mice increases BACE1 protein levels (not just activity), enhances APP processing at the β-secretase site, and facilitates amyloid deposition in Alzheimer mouse models, confirming an in vivo role for RTN3 in regulating BACE1. RTN3-null mouse generation, biochemical BACE1 activity assay, APP processing analysis (Western blot), amyloid plaque quantification by immunohistochemistry The Journal of neuroscience High 25319692
2017 The full-length (long) isoform of RTN3 is a specific ER-phagy receptor for the degradation of ER tubules. RTN3 oligomerization triggers fragmentation of ER tubules; its long N-terminal region contains multiple LIR motifs that bind LC3s/GABARAPs, which is essential for delivery of fragmented ER tubules to lysosomes. This function is independent of the ER sheet receptor FAM134B. Live-cell imaging (super-resolution), co-immunoprecipitation, mutagenesis of LIR motifs, autophagy flux assays, siRNA knockdown, fluorescence microscopy, starvation-induced autophagy assays eLife High 28617241
2017 RTN3 is a cold-induced protein whose mRNA evades cooling-induced translational elongation repression and is directly bound by the cold shock protein RBM3, which drives increased RTN3 expression; RTN3 knockdown eliminates cooling-induced neuroprotection in mice, while lentiviral RTN3 overexpression independently prevents synaptic loss and cognitive deficits in a neurodegeneration mouse model. Ribosome profiling (translatome analysis), RNA immunoprecipitation (RIP), lentiviral overexpression, siRNA knockdown, mouse behavioral assays, synapse counting Current biology : CB High 28238655
2017 RTN3 deficiency causes elevation of BACE1 protein levels, whereas RTN1 deficiency shows no obvious effect on BACE1 due to compensatory upregulation of RTN3; RTN3 is enriched in dystrophic neurites of Alzheimer plaques while RTN1 is not. RTN1-null and RTN3-null mouse generation, Western blot, BACE1 activity assay, immunohistochemistry of Alzheimer brain tissue Scientific reports Medium 28733667
2018 RTN3 overexpression in mice induces obesity and hypertriglyceridemia; mechanistically, RTN3 interacts with HSPA5 (GRP78/BiP), and this enhanced interaction increases SREBP1c and AMPK activity, promoting triglyceride biosynthesis and lipid droplet expansion. RTN3 transgenic and null mice, 3T3-L1 cell culture, co-immunoprecipitation (RTN3-HSPA5), C. elegans strains, Western blot for SREBP1c and AMPK Circulation Medium 29716941
2018 BAP31 is a binding partner of RTN3 that stabilizes RTN3 monomer; BAP31 knockout in primary neurons decreases RTN3 monomer availability and enhances RTN3 aggregates, leading to increased BACE1-mediated APP processing and greater amyloid plaque formation in vivo. Co-immunoprecipitation (BAP31-RTN3), conditional BAP31 knockout mice crossed to APP/PS1 AD model, Western blot for RTN3 aggregates, amyloid plaque immunohistochemistry FASEB journal Medium 30596517
2018 RTN3 variants found in Alzheimer's disease patients alter RTN3 function: the 5'-UTR variant c.-8G>T reduces RTN3 expression, and the T39M variant impairs axonal transport of BACE1 in cultured neurons. Luciferase reporter assay (for expression effect of 5'-UTR variant), kymograph analysis of BACE1-RFP particle mobility in neurons transfected with wild-type or mutant RTN3 Human genetics Medium 29356939
2021 RTN3 is upregulated during RNA viral infection and acts as a negative regulator of RIG-I-mediated antiviral signaling; RTN3 aggregates on the ER, interacts with both TRIM25 and RIG-I, impairs TRIM25-mediated K63-linked polyubiquitination of RIG-I, and thereby inhibits both IRF3 and NF-κB activation. Co-immunoprecipitation (RTN3-TRIM25, RTN3-RIG-I), ubiquitination assay (K63-linked), IRF3/NF-κB reporter assays, RTN3 overexpression mouse model (VSV challenge), neutrophil and inflammatory cell quantification eLife High 34313226
2022 Loss of RTN3 phenocopies chronic kidney disease; mechanistically, RTN3 interacts with GPBP1, which activates the IGF2-JAK2-STAT3 pathway, regulating collagen biosynthesis and mitochondrial function in proximal tubular epithelial cells. RTN3-null mouse model, co-immunoprecipitation (RTN3-GPBP1), primary tubular epithelial cell culture, pathway inhibitor assays, collagen and mitochondrial function measurements Experimental & molecular medicine Medium 35596061
2023 RTN3 directly binds FABP5 to facilitate directed transport of fatty acids to the ER, promoting lipid droplet biogenesis via DGAT2 in a lipid overload (high-fat diet) context in the heart; upstream, C/EBPα positively regulates RTN3 transcription by binding its promoter. Co-immunoprecipitation (RTN3-FABP5), loss- and gain-of-function experiments in mice, DGAT2 inhibitor rescue, C/EBPα promoter binding (ChIP-like assay), cardiac function assays Cell death and differentiation Medium 38017147
2023 Increased RTN3 in the liver induces NAFLD phenotypes by interacting with GRP78 (HSPA5), which inhibits the AMPK-IDH2 pathway, leading to mitochondrial dysfunction and lipid accumulation; RTN3 knockout relieves fatty liver and mitochondrial dysfunction. RTN3 transgenic and knockout mice, primary hepatocyte culture, co-immunoprecipitation (RTN3-GRP78), AMPK/IDH2 pathway analysis, single-cell RNA sequencing, C. elegans models MedComm Medium 36925557
2024 Exosomal miR-4488 from hypoxic pNEN tumor cells promotes macrophage M2 polarization by directly targeting and suppressing RTN3; RTN3 suppression enhances fatty acid oxidation and activates the PI3K/AKT/mTOR pathway through interaction with and downregulation of FABP5, promoting liver metastasis. miRNA target validation (luciferase reporter), co-immunoprecipitation (RTN3-FABP5), macrophage polarization assays, fatty acid oxidation measurements, signaling pathway analysis, in vivo metastasis model International journal of biological sciences Medium 38904015

Source papers

Stage 0 corpus · 100 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 360 28617241
2007 Fabrication and characterization of PLGA/HAp composite scaffolds for delivery of BMP-2 plasmid DNA. Journal of controlled release : official journal of the Controlled Release Society 171 17512077
2020 Accelerated degradation of HAP/PLLA bone scaffold by PGA blending facilitates bioactivity and osteoconductivity. Bioactive materials 169 32995675
2008 Identification, characterization and interaction of HAP family genes in rice. Molecular genetics and genomics : MGG 131 18193457
2017 Heteroaryldihydropyrimidine (HAP) and Sulfamoylbenzamide (SBA) Inhibit Hepatitis B Virus Replication by Different Molecular Mechanisms. Scientific reports 128 28205569
1997 Fast transport and retrograde movement of huntingtin and HAP 1 in axons. Neuroreport 118 9243620
2008 Three-dimensional fibrous PLGA/HAp composite scaffold for BMP-2 delivery. Biotechnology and bioengineering 115 17570710
1999 A novel hnRNP protein (HAP/SAF-B) enters a subset of hnRNP complexes and relocates in nuclear granules in response to heat shock. Journal of cell science 105 10212141
1998 The Haemophilus influenzae Hap serine protease promotes adherence and microcolony formation, potentiated by a soluble host protein. Molecular cell 96 9885571
1997 Structural determinants of processing and secretion of the Haemophilus influenzae hap protein. Molecular microbiology 92 9402021
2002 The Haemophilus influenzae Hap autotransporter binds to fibronectin, laminin, and collagen IV. Infection and immunity 86 12183535
2001 The Hypocrea jecorina HAP 2/3/5 protein complex binds to the inverted CCAAT-box (ATTGG) within the cbh2 (cellobiohydrolase II-gene) activating element. Molecular genetics and genomics : MGG 86 11589578
1999 Cloning of a novel member of the reticulon gene family (RTN3): gene structure and chromosomal localization to 11q13. Genomics 71 10331947
2018 Bilayered PLGA/PLGA-HAp Composite Scaffold for Osteochondral Tissue Engineering and Tissue Regeneration. ACS biomaterials science & engineering 69 33465902
2013 Local delivery of controlled-release simvastatin/PLGA/HAp microspheres enhances bone repair. International journal of nanomedicine 65 24143094
2017 RTN3 Is a Novel Cold-Induced Protein and Mediates Neuroprotective Effects of RBM3. Current biology : CB 63 28238655
2012 Fluoridated HAp:Ln3+ (Ln = Eu or Tb) nanoparticles for cell-imaging. Nanoscale 63 23076865
2003 The Haemophilus influenzae Hap autotransporter mediates microcolony formation and adherence to epithelial cells and extracellular matrix via binding regions in the C-terminal end of the passenger domain. Cellular microbiology 59 12614461
2011 Crystal structure of the Haemophilus influenzae Hap adhesin reveals an intercellular oligomerization mechanism for bacterial aggregation. The EMBO journal 56 21841773
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
2003 AHP's, HAP's and DAP's: how potassium currents regulate the excitability of rat supraoptic neurones. Journal of computational neuroscience 53 14618071
2015 From hair to heart: nestin-expressing hair-follicle-associated pluripotent (HAP) stem cells differentiate to beating cardiac muscle cells. Cell cycle (Georgetown, Tex.) 52 25970547
2001 The Hemophilus influenzae Hap autotransporter is a chymotrypsin clan serine protease and undergoes autoproteolysis via an intermolecular mechanism. The Journal of biological chemistry 52 11504735
1998 The penicillin regulator PENR1 of Aspergillus nidulans is a HAP-like transcriptional complex. European journal of biochemistry 50 9490049
2002 Immunization with Haemophilus influenzae Hap adhesin protects against nasopharyngeal colonization in experimental mice. The Journal of infectious diseases 47 12355362
2020 Regenerated cellulose nanofibers from cellulose acetate: Incorporating hydroxyapatite (HAp) and silver (Ag) nanoparticles (NPs), as a scaffold for tissue engineering applications. Materials science & engineering. C, Materials for biological applications 46 33255098
2004 CaO--P2O5--Na2O-based sintering additives for hydroxyapatite (HAp) ceramics. Biomaterials 44 14741598
2019 Functionalization of SF/HAP Scaffold with GO-PEI-miRNA inhibitor Complexes to Enhance Bone Regeneration through Activating Transcription Factor 4. Theranostics 42 31285777
2019 The Hap Complex in Yeasts: Structure, Assembly Mode, and Gene Regulation. Frontiers in microbiology 42 31379791
2017 Litchi-like Fe3O4@Fe-MOF capped with HAp gatekeepers for pH-triggered drug release and anticancer effect. Journal of materials chemistry. B 42 32264528
2016 Bioactivity assessment of PLLA/PCL/HAP electrospun nanofibrous scaffolds for bone tissue engineering. Life sciences 41 26874032
2009 Electrically polarized HAp-coated Ti: in vitro bone cell-material interactions. Acta biomaterialia 41 19671456
2018 Novel non-heteroarylpyrimidine (HAP) capsid assembly modifiers have a different mode of action from HAPs in vitro. Antiviral research 39 30031759
2007 Synthesis and cellular biocompatibility of two kinds of HAP with different nanocrystal morphology. Journal of biomedical materials research. Part B, Applied biomaterials 39 17330894
2021 3D-printed bioactive ceramic scaffolds with biomimetic micro/nano-HAp surfaces mediated cell fate and promoted bone augmentation of the bone-implant interface in vivo. Bioactive materials 37 35087968
2020 Arabinoxylan-co-AA/HAp/TiO2 nanocomposite scaffold a potential material for bone tissue engineering: An in vitro study. International journal of biological macromolecules 36 32081758
2017 RTN1 and RTN3 protein are differentially associated with senile plaques in Alzheimer's brains. Scientific reports 36 28733667
2017 Hair follicle-associated-pluripotent (HAP) stem cells. Cell cycle (Georgetown, Tex.) 36 28749199
2007 The membrane topology of RTN3 and its effect on binding of RTN3 to BACE1. The Journal of biological chemistry 36 17699523
2018 Identification of rare RTN3 variants in Alzheimer's disease in Han Chinese. Human genetics 35 29356939
2003 Pro-apoptotic ASY/Nogo-B protein associates with ASYIP. Journal of cellular physiology 35 12811824
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 32 38904015
2018 Increased Reticulon 3 (RTN3) Leads to Obesity and Hypertriglyceridemia by Interacting With Heat Shock Protein Family A (Hsp70) Member 5 (HSPA5). Circulation 32 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
2008 Characterization of a HAP-phytase from a thermophilic mould Sporotrichum thermophile. Bioresource technology 32 19054669
2020 Impact of structural features of Sr/Fe co-doped HAp on the osteoblast proliferation and osteogenic differentiation for its application as a bone substitute. Materials science & engineering. C, Materials for biological applications 31 32204069
2017 Effects of HAp and TCP in constructing tissue engineering scaffolds for bone repair. Journal of materials chemistry. B 31 32264364
2003 Chromosomal expression of the Haemophilus influenzae Hap autotransporter allows fine-tuned regulation of adhesive potential via inhibition of intermolecular autoproteolysis. Journal of bacteriology 31 12591878
2001 In vivo expression of Neisseria meningitidis proteins homologous to the Haemophilus influenzae Hap and Hia autotransporters. FEMS immunology and medical microbiology 31 11750223
2016 Isoproterenol directs hair follicle-associated pluripotent (HAP) stem cells to differentiate in vitro to cardiac muscle cells which can be induced to form beating heart-muscle tissue sheets. Cell cycle (Georgetown, Tex.) 30 27104748
2015 In vitro and in vivo evaluation of the developed PLGA/HAp/Zein scaffolds for bone-cartilage interface regeneration. Biomedical and environmental sciences : BES 29 25566858
2013 A PLG/HAp composite scaffold for lentivirus delivery. Biomaterials 25 23602363
2009 HDPE-Al2O3-HAp composites for biomedical applications: processing and characterizations. Journal of biomedical materials research. Part B, Applied biomaterials 25 18338785
2020 Synthesis and characterization of PLGA/HAP scaffolds with DNA-functionalised calcium phosphate nanoparticles for bone tissue engineering. Journal of materials science. Materials in medicine 24 33140175
2011 Development and implementation of a performance improvement project in adult intensive care units: overview of the Improving Medicine Through Pathway Assessment of Critical Therapy in Hospital-Acquired Pneumonia (IMPACT-HAP) study. Critical care (London, England) 24 21266065
2021 The efficiency of PCL/HAp electrospun nanofibers in bone regeneration: a review. Journal of medical engineering & technology 23 34251971
2020 Phosphonic Acid Coupling Agent Modification of HAP Nanoparticles: Interfacial Effects in PLLA/HAP Bone Scaffold. Polymers 23 31940986
2015 Influence of Growth Parameters on the Formation of Hydroxyapatite (HAp) Nanostructures and Their Cell Viability Studies. Nanobiomedicine 23 29942368
2017 Effects of altered RTN3 expression on BACE1 activity and Alzheimer's neuritic plaques. Reviews in the neurosciences 22 27883331
2015 Relative Contribution of P5 and Hap Surface Proteins to Nontypable Haemophilus influenzae Interplay with the Host Upper and Lower Airways. PloS one 22 25894755
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
1990 Capsules and virulence in the HAP group of bacteria. Canadian journal of veterinary research = Revue canadienne de recherche veterinaire 22 2193699
2023 Construction of 3D bioprinting of HAP/collagen scaffold in gelation bath for bone tissue engineering. Regenerative biomaterials 21 37655210
2022 Multifunctional Bioactive Scaffolds from ARX-g-(Zn@rGO)-HAp for Bone Tissue Engineering: In Vitro Antibacterial, Antitumor, and Biocompatibility Evaluations. ACS applied bio materials 21 36215135
2013 Phosphorylation and ionic strength alter the LRAP-HAP interface in the N-terminus. Biochemistry 21 23477367
2023 Increased RTN3 phenocopies nonalcoholic fatty liver disease by inhibiting the AMPK-IDH2 pathway. MedComm 20 36925557
2007 Anti-apoptotic activity of Bcl-2 is enhanced by its interaction with RTN3. Cell biology international 20 17379544
2021 LINC02288 promotes chondrocyte apoptosis and inflammation through miR-374a-3p targeting RTN3. The journal of gene medicine 19 33491257
2021 Hair-Follicle-Associated Pluripotent (HAP) Stem Cells Can Extensively Differentiate to Tyrosine-Hydroxylase-Expressing Dopamine-Secreting Neurons. Cells 19 33920157
2014 The HAP complex in Fusarium verticillioides is a key regulator of growth, morphogenesis, secondary metabolism, and pathogenesis. Fungal genetics and biology : FG & B 19 24875423
2018 Axial Suspension Plasma Spraying: An ultimate technique to tailor Ti6Al4V surface with HAp for orthopaedic applications. Colloids and surfaces. B, Biointerfaces 18 30551296
2004 HXT5 expression is under control of STRE and HAP elements in the HXT5 promoter. Yeast (Chichester, England) 18 15282798
2002 Generation of multiple mRNA transcripts from the novel human apoptosis-inducing gene hap by alternative polyadenylation utilization and the translational activation function of 3' untranslated region. Archives of biochemistry and biophysics 18 12054434
2023 Characterization of effector protein Hap determining meat spoilage process from meat-borne Aeromonas salmonicida. Food chemistry 17 36641914
2023 Fabrication and In Vitro Drug Delivery Evaluation of Cephalexin Monohydrate-Loaded PLA:PVA/HAP:TiO2 Fibrous Scaffolds for Bone Regeneration. ACS omega 16 36777593
2020 Quorum-sensing signaling by chironomid egg masses' microbiota, affects haemagglutinin/protease (HAP) production by Vibrio cholerae. Molecular ecology 16 33001525
2017 Implanted hair-follicle-associated pluripotent (HAP) stem cells encapsulated in polyvinylidene fluoride membrane cylinders promote effective recovery of peripheral nerve injury. Cell cycle (Georgetown, Tex.) 16 28886268
1990 Effects of hap mutations on heme and cytochrome formation in yeast. Current genetics 16 2182199
1977 Nucleotide sequence of the SV40 DNA restriction fragment Hind C-Hap 2. Nucleic acids research 16 194226
2009 RTN3 inducing apoptosis is modulated by an adhesion protein CRELD1. Molecular and cellular biochemistry 15 19521671
2009 Structural determinants of autoproteolysis of the Haemophilus influenzae Hap autotransporter. Infection and immunity 15 19687208
2005 Identification of a new RTN3 transcript, RTN3-A1, and its distribution in adult mouse brain. Brain research. Molecular brain research 15 15946766
2023 Lipid overload-induced RTN3 activation leads to cardiac dysfunction by promoting lipid droplet biogenesis. Cell death and differentiation 14 38017147
2021 Effect of carbon based fillers on xylan/chitosan/nano-HAp composite matrix for bone tissue engineering application. International journal of biological macromolecules 14 34914910
2013 Nogo/RTN4 isoforms and RTN3 expression protect SH-SY5Y cells against multiple death insults. Molecular and cellular biochemistry 14 23955438
2002 The novel endoplasmic reticulum (ER)-targeted protein HAP induces cell apoptosis by the depletion of the ER Ca(2+) stores. FEBS letters 14 12372622
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
2019 Hair-Follicle-Associated Pluripotent (HAP) Stem Cells Encapsulated on Polyvinylidene Fluoride Membranes (PFM) Promote Functional Recovery from Spinal Cord Injury. Stem cell reviews and reports 13 30341634
2019 Atorvastatin loaded PLGA microspheres: Preparation, HAp coating, drug release and effect on osteogenic differentiation of ADMSCs. International journal of pharmaceutics 13 31071416
2010 Novel insights into Haemagglutinin Protease (HAP) gene regulation in Vibrio cholerae. Molecular ecology 13 20819164
2024 DLP Fabrication of Multiple Hierarchical Biomimetic GelMA/SilMA/HAp Scaffolds for Enhancing Bone Regeneration. Biomacromolecules 12 38324764
2023 RUNX2 and ALP expression in osteoblast cells exposed by PMMA-HAp combination: An in vitro study. Journal of oral biology and craniofacial research 12 36896352
2020 Complex approach for analysis of snake venom α-neurotoxins binding to HAP, the high-affinity peptide. Scientific reports 12 32123252
2019 Expression of anti-aging type-XVII collagen (COL17A1/BP180) in hair follicle-associated pluripotent (HAP) stem cells during differentiation. Tissue & cell 12 31383286
2019 Cell adhesion evaluation of laser-sintered HAp and 45S5 bioactive glass coatings on micro-textured zirconia surfaces using MC3T3-E1 osteoblast-like cells. Materials science & engineering. C, Materials for biological applications 12 32228989
2016 Hypoxia Enhances Differentiation of Hair Follicle-Associated-Pluripotent (HAP) Stem Cells to Cardiac-Muscle Cells. Journal of cellular biochemistry 12 27627796
2006 Adaptor FADD is recruited by RTN3/HAP in ER-bound signaling complexes. Apoptosis : an international journal on programmed cell death 12 17031492