Affinage

LRP8

Low-density lipoprotein receptor-related protein 8 · UniProt Q14114

Length
963 aa
Mass
105.6 kDa
Annotated
2026-04-28
100 papers in source corpus 47 papers cited in narrative 47 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LRP8 (ApoER2) is a multifunctional LDL receptor family member that serves as a signaling receptor, endocytic transporter, and viral entry receptor across neuronal, endothelial, platelet, and testicular cell types. In the brain, LRP8 binds Reelin (and alternative ligands including thrombospondin-1 and clusterin) to induce Dab1 tyrosine phosphorylation, PI3K/Akt activation, and NMDA receptor modulation, thereby controlling neuronal migration, dendritic architecture, and synaptic plasticity including LTP — functions that depend critically on alternatively spliced exon 19 and lipid raft localization (PMID:16102539, PMID:12670700, PMID:17913789, PMID:19948739). Regulated intramembrane proteolysis by metalloproteinases and γ-secretase releases a transcriptionally active intracellular domain (ICD) that suppresses reelin transcription and activates neuronal enhancers governing memory-related genes (PMID:24344333, PMID:25892301, PMID:25429077). Beyond the nervous system, LRP8 mediates selenoprotein P-dependent selenium uptake essential for GPX4 translation and ferroptosis resistance (PMID:17314095, PMID:37435859), scaffolds PP2A assembly to regulate eNOS phosphorylation and thrombosis in endothelial cells and platelets (PMID:21123944, PMID:29500169), and functions as an entry receptor for alphaviruses and tick-borne encephalitis virus (PMID:34929721, PMID:40993380).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2000 Medium

    Identifying ApoER2-specific cytoplasmic interactors established that LRP8 assembles signaling scaffolds distinct from VLDLR, revealing JIP-1/JIP-2 as intracellular binding partners that could link ApoER2 to JNK-dependent signaling cascades.

    Evidence Yeast two-hybrid and co-immunoprecipitation with domain mapping in neuronal cells

    PMID:10827199

    Open questions at the time
    • Functional consequence of JIP binding on Reelin signaling not tested
    • No in vivo confirmation of ApoER2-JIP complex relevance
  2. 2003 High

    Demonstrating that purified Reelin binds ApoER2 with higher affinity than VLDLR and that both receptors jointly mediate Dab1 phosphorylation established the cooperative yet non-redundant receptor model for Reelin signaling.

    Evidence Purified Reelin binding assays with cortical neurons from single and double receptor knockout mice, Dab1 phosphorylation immunoblotting

    PMID:12670700

    Open questions at the time
    • Structural basis for differential Reelin affinity between receptors unknown at this time
    • Downstream pathway divergence between receptors not fully resolved
  3. 2005 High

    Four contemporaneous studies established fundamental aspects of ApoER2 cell biology: its postsynaptic localization with NMDA receptors and dependence on exon 19 for LTP; its clathrin-dependent endocytosis via Dab2 and the NPxY motif; and its interaction with F-spondin and β2GPI domain V, broadening the receptor's ligand repertoire and signaling contexts.

    Evidence Co-immunoprecipitation, LTP electrophysiology, exon 19 knock-in mice, endocytosis assays with dominant-negative constructs, platelet adhesion assays with domain-deletion mutants

    PMID:16091370 PMID:16101684 PMID:16102539 PMID:16227578

    Open questions at the time
    • How exon 19 structurally couples ApoER2 to NMDA receptor tyrosine phosphorylation machinery was unclear
    • Whether Dab2-mediated endocytosis is the sole internalization route in all cell types
  4. 2007 High

    Three advances expanded ApoER2 function beyond brain signaling: identification as the testicular selenoprotein P receptor mediating selenium uptake; discovery that PCSK9 targets ApoER2 for lysosomal degradation independently of catalytic activity; demonstration that ApoER2 (not VLDLR) specifically controls late-born neuronal migration; and that ApoER2 interacts with APP to modulate Aβ production.

    Evidence Affinity chromatography/MS identification of Sepp1 receptor confirmed by ApoER2-KO mice with selenium deficiency; PCSK9 chimeras and catalytic mutants; BrdU fate mapping in single/double KO mice; co-IP and surface biotinylation with APP processing assays

    PMID:17314095 PMID:17620134 PMID:17913789 PMID:18039658

    Open questions at the time
    • Mechanism of selenium release from Sepp1 after ApoER2-mediated endocytosis not established
    • Whether PCSK9-mediated ApoER2 degradation occurs in neurons in vivo
    • Relative contribution of ApoER2-APP interaction to AD pathogenesis unclear
  5. 2008 High

    Identification of thrombospondin-1 and activated protein C as new ApoER2 ligands revealed ligand-specific signaling diversity: THBS-1 induces Dab1 phosphorylation without degradation or Akt activation, while APC signals through Dab1-Y220/PI3K/Akt/GSK3β, establishing ApoER2 as a context-dependent signaling hub.

    Evidence Direct binding assays, SVZ explant chain assays with THBS-1-KO mice; SPR binding (Kd ~30 nM for APC), siRNA knockdown, kinase inhibitor dissection

    PMID:18706682 PMID:18946489 PMID:19116273

    Open questions at the time
    • How different ligands activate distinct downstream cascades through the same receptor is mechanistically unexplained
    • In vivo significance of APC-ApoER2 axis in neuroprotection not fully tested
  6. 2009 High

    Genetic dissection using cytoplasmic domain knock-in mice showed that ApoER2's selenium transport and Reelin signaling functions are separable, resolving whether neurological phenotypes arise from selenium deficiency or impaired Reelin signaling. Concurrently, Factor XI was identified as a platelet ApoER2 ligand, and splice variant-specific Reelin binding profiles were characterized.

    Evidence Knock-in mice with signaling motif mutations retaining normal tissue selenium; SPR showing FXI binds ApoER2 with ~61 nM affinity confirmed by KO platelet adhesion assays; quantitative binding with purified Reelin fragments and ApoER2 splice variants

    PMID:19007311 PMID:19167437 PMID:19661487 PMID:19948739

    Open questions at the time
    • Whether selenium transport requires specific splice variants of ApoER2 unknown
    • In vivo thrombotic consequence of FXI-ApoER2 interaction not fully characterized
  7. 2010 High

    Two discoveries established post-translational regulatory mechanisms controlling ApoER2 surface levels: the E3 ligase IDOL ubiquitinates ApoER2 for lysosomal degradation under LXR control, directly modulating Reelin signaling; and β2GPI-aPL antibody engagement of endothelial ApoER2 activates PP2A to dephosphorylate eNOS, identifying a pathogenic signaling axis in antiphospholipid syndrome with thrombosis protection in ApoER2-KO mice.

    Evidence Ubiquitination assays and LXR activation in vivo; ApoER2-KO mice with intravital microscopy and PP2A activity assays

    PMID:20427281 PMID:21123944

    Open questions at the time
    • Whether IDOL regulation of ApoER2 occurs in neurons with physiological relevance to Reelin was not yet tested
    • Cell-type specificity of PP2A assembly on ApoER2 tail unknown
  8. 2012 Medium

    Three findings expanded ApoER2's cellular roles: muscle cell selenium uptake via Sepp1 endocytosis requiring lysosomal acidification; positive regulation of Wnt/β-catenin signaling affecting osteoblast differentiation; and endothelial ApoE-mediated angiogenic control through LRP8.

    Evidence 75Se-Sepp1 uptake with siRNA and lysosomal inhibitors in L8 myoblasts; Wnt reporter and osteoblast mineralization assays; in vivo LNA inhibition and cancer-endothelial co-culture

    PMID:22589174 PMID:22761431 PMID:23142051

    Open questions at the time
    • Structural basis for ApoER2 participation in Wnt signaling unclear
    • Whether LRP8-Wnt interaction is direct or through co-receptor mechanisms unknown
  9. 2013 High

    The discovery that γ-secretase cleavage of ApoER2 produces an ICD that binds the RELN promoter and suppresses reelin transcription established a negative feedback loop in Reelin signaling; concurrently, CIN85 was identified as a Dab1-dependent adaptor recruited to ApoER2-positive early endosomes.

    Evidence ChIP showing ICD binding to RELN promoter, PS1 conditional KO mice, luciferase reporter; co-IP and immunofluorescence colocalization with Reelin stimulation

    PMID:23506116 PMID:24344333 PMID:24381170

    Open questions at the time
    • Whether ICD-mediated RELN repression operates in all brain regions
    • CIN85 functional role in ApoER2 trafficking vs. signaling not resolved
  10. 2014 High

    Multiple studies refined ApoER2's splicing-dependent functions and trafficking: O-linked sugar domain splicing (exon 16) controls ectodomain shedding, ICD release, spine density, and fear memory; SNX17 promotes ApoER2 recycling via the NPxY motif; neurotrophin-TrkB signaling induces ApoER2 shedding independently of MAPK/PI3K; and ApoE isoform-specific signaling through endothelial ApoER2 reveals ApoE4 as a dominant-negative antagonist.

    Evidence Splice variant knock-in mice with behavioral/electrophysiological phenotypes; GST pull-down and trafficking assays; pharmacological TrkA/TrkB dissection; eNOS assays with ApoER2-KO mice and carotid reendothelialization model

    PMID:24705369 PMID:25197062 PMID:25233900 PMID:25429077

    Open questions at the time
    • How O-linked glycosylation mechanistically regulates metalloproteinase access for shedding
    • Whether neurotrophin-induced shedding occurs in vivo and its functional significance
  11. 2015 High

    The synapse-to-nucleus signaling model was completed by demonstrating that Reelin-triggered γ-secretase release of the ApoER2 ICD activates neuronal enhancers (LRN enhancers) controlling synaptic plasticity genes during memory formation; separately, Reelin-ApoER2 was shown to regulate Schwann cell migration through Rac1/Tiam1/PAR3.

    Evidence ChIP with enhancer profiling, γ-secretase inhibition, LRP8 knockdown, in vivo behavioral assays; FRET-based Rac1 activation and siRNA knockdown in Schwann cells

    PMID:25892301 PMID:26386179

    Open questions at the time
    • Identity of transcription factors cooperating with ApoER2 ICD at LRN enhancers unknown
    • Whether ApoER2 ICD genomic targets differ between brain regions
  12. 2016 Medium

    Two studies connected ApoER2 splicing and postsynaptic scaffolding to disease-relevant function: antisense oligonucleotides correcting exon 19 splicing rescued synaptic and memory deficits in AD mice, and disruption of ApoER2/Dab1/PSD95 interaction destabilized dendritic architecture and reintroduced immature NR2B-NMDARs.

    Evidence ASO treatment with LTP and behavioral rescue in AD mouse model; tailless ApoER2 mutant with dendritic morphology and NMDAR subunit analysis

    PMID:26902204 PMID:27653801

    Open questions at the time
    • Mechanism by which exon 19 mis-splicing occurs in AD brain not identified
    • Whether ASO approach is viable for human therapeutic development
  13. 2017 High

    Three advances provided structural and mechanistic depth: the crystal structure of the ApoER2 ectodomain–Reelin complex revealed a contracted-open conformation with pH-dependent ligand release; IDOL was shown to regulate synaptic ApoER2 levels for experience-dependent spine remodeling and LTP; and GRIP1 was found to bridge ApoER2 with ephrinB2 and AMPA receptors in an activity-dependent postsynaptic complex essential for LTP.

    Evidence X-ray crystallography with mutagenesis and pH-binding assays; IDOL-KO mice with spine imaging, barrel cortex plasticity, and behavioral tests; phospho-mutant knock-in mice with co-IP and LTP electrophysiology

    PMID:28446613 PMID:28891791 PMID:28978486

    Open questions at the time
    • Full-length Reelin–receptor complex structure not yet available
    • How IDOL activity is regulated by neuronal firing patterns unknown
  14. 2018 High

    Detailed dissection of the ApoER2 cytoplasmic tail as a PP2A scaffolding platform in endothelial cells revealed that Dab2 recruits to NPxY to activate PP2A-C via LCMT-1 methylation, while SHC1 recruits PP2A regulatory subunits to the proline-rich C-terminus, mediating aPL-induced eNOS and Akt dephosphorylation.

    Evidence Domain-specific mutants, co-IP, siRNA knockdown, in vivo thrombosis model

    PMID:29500169

    Open questions at the time
    • Whether this PP2A assembly mechanism operates identically in platelets and trophoblasts
    • Structural basis for the bipartite PP2A recruitment unknown
  15. 2019 Medium

    Three studies addressed receptor oligomerization dynamics, cell cycle regulation, and post-transcriptional control: Reelin rearranges ApoER2 homo-oligomers into higher-order clusters required for Dab1 phosphorylation; ApoER2 scaffolds PP2A-CDC20 interaction for APC activation and smooth muscle cell cycle progression; and SFRS11 stabilizes LRP8 mRNA via 3′ UTR binding, linking RNA metabolism to cognitive function.

    Evidence FLIM/FRET oligomerization analysis; co-IP with cell cycle arrest phenotyping in Lrp8-KO vascular model; RNA immunoprecipitation and behavioral rescue

    PMID:30873003 PMID:31269452 PMID:31412739

    Open questions at the time
    • Whether receptor clustering stoichiometry differs across cell types
    • PP2A-CDC20 scaffolding by ApoER2 awaits independent confirmation
    • How SFRS11 deficiency selectively affects LRP8 among its targets
  16. 2021 High

    Two discoveries extended ApoER2 biology to viral entry and placental pathology: alphavirus E2-E1 glycoproteins bind ApoER2/VLDLR ligand-binding domains for neuronal infection (blockable by soluble LBD-Fc), and ApoER2-PP2A signaling in trophoblasts drives preeclampsia in antiphospholipid syndrome.

    Evidence CRISPR KO screen, virus-like particle assays, in vivo SFV protection with LBD-Fc; APS mouse preeclampsia model with ApoER2-specific interventions

    PMID:34404233 PMID:34929721

    Open questions at the time
    • Whether ApoER2 versus VLDLR differentially determines neurotropism of specific alphaviruses
    • Molecular determinants of PP2A activation in trophoblasts vs. endothelium
  17. 2022 Medium

    Comprehensive long-read sequencing identified 25 human APOER2 splice isoforms, revealing that exon 5–8 deletion variants produce maximal CTF/ICD and transcriptional activation, while isoform-specific rescue of Apoer2-KO neurons showed differential ability to restore miniature excitatory events, establishing isoform-specific synaptic functions.

    Evidence Gene-specific long-read sequencing, CTF immunoblotting, ICD transcriptional reporter, miniature excitatory event recording with lentiviral rescue in KO neurons

    PMID:35414534

    Open questions at the time
    • Isoform-specific contributions to non-neuronal ApoER2 functions untested
    • Regulation of isoform selection during development or disease not characterized
  18. 2023 High

    Two studies revealed mechanistic details of ApoER2-dependent selenium biology: LRP8 protects MYCN-amplified neuroblastoma from ferroptosis by supplying selenocysteine for GPX4 translation via selenoprotein P uptake; and high-affinity glycosylated ApoER2 variants use a Sec lyase-independent selenium transport mechanism distinct from low-affinity variants.

    Evidence CRISPR-activation screen with inducible KO and xenograft models; Kd measurements with 75Se uptake and Sec lyase/lysosomal inhibitors

    PMID:37406814 PMID:37435859

    Open questions at the time
    • Whether ferroptosis resistance via LRP8-SELENOP axis operates in normal neural stem cells
    • Structural basis for affinity-dependent routing through different selenium release pathways
  19. 2025 High

    Genome-scale CRISPR screening identified LRP8 as a direct entry receptor for tick-borne encephalitis virus, binding the TBEV E glycoprotein and mediating attachment and internalization — extending ApoER2's role as a broad viral receptor.

    Evidence Genome-scale CRISPR-Cas9 screen, direct E glycoprotein binding, gain/loss-of-function infection assays, LRP8-based decoy receptor protection in mice

    PMID:40993380

    Open questions at the time
    • Whether LRP8 serves as receptor for additional flaviviruses beyond TBEV
    • Mechanism of viral genome release after ApoER2-mediated endocytosis unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: how the same receptor activates distinct downstream pathways depending on ligand identity; the full structural basis of ApoER2 ICD nuclear function and its chromatin targets across brain regions; and the therapeutic potential of splice-switching or decoy receptor strategies in neurodegeneration and viral infection.
  • No full-length Reelin–ApoER2 complex structure available
  • ICD cofactors and chromatin remodeling partners at LRN enhancers unidentified
  • Cell-type-specific isoform expression maps not systematically generated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 8 GO:0001618 virus receptor activity 2 GO:0060090 molecular adaptor activity 2
Localization
GO:0005886 plasma membrane 4 GO:0005768 endosome 3 GO:0005634 nucleus 2
Pathway
R-HSA-162582 Signal Transduction 9 R-HSA-112316 Neuronal System 5 R-HSA-382551 Transport of small molecules 4 R-HSA-109582 Hemostasis 3 R-HSA-1266738 Developmental Biology 2 R-HSA-168256 Immune System 2 R-HSA-5357801 Programmed Cell Death 1
Partners
DAB1GRIP1IDOLPCSK9PSD95RELNSELENOPSNX17
Complex memberships
ApoER2-GRIP1-ephrinB2-AMPAR complexApoER2-NMDAR postsynaptic complexApoER2-PP2A signaling complex

Evidence

Reading pass · 47 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 ApoER2 (LRP8) is present in the postsynaptic densities of excitatory synapses where it forms a functional complex with NMDA receptors; Reelin signaling through ApoER2 enhances LTP through an alternatively spliced intracellular exon (exon 19) that is required for Reelin-induced tyrosine phosphorylation of NMDA receptor subunits Co-immunoprecipitation, alternative splicing analysis, LTP electrophysiology, knock-in mice lacking the exon, behavioral testing Neuron High 16102539
2000 ApoER2 (but not VLDLR) binds JNK-interacting proteins JIP-1 and JIP-2 through its intracellular domain, assembling a multiprotein complex at the neuronal cell surface that may participate in ApoER2-specific Reelin signaling Co-immunoprecipitation, yeast two-hybrid, domain mapping The Journal of biological chemistry Medium 10827199
2003 Purified Reelin binds ApoER2 more readily than VLDLR and induces tyrosine phosphorylation of Dab1 through both receptors; ApoER2 and VLDLR are jointly essential for Reelin-induced Dab1 phosphorylation with no compensatory receptor Purified Reelin binding assays, cortical neuron cultures from single/double receptor knockout mice, Dab1 phosphorylation immunoblotting, layer-specific marker analysis Brain research. Molecular brain research High 12670700
2007 PCSK9 binds to ApoER2 (as well as LDLR and VLDLR) and induces its lysosomal degradation either by cellular co-expression or re-internalization of secreted PCSK9; membrane-bound PCSK9 chimeras greatly enhance receptor targeting to late endosomes/lysosomes; catalytic activity of PCSK9 is not required for degradation Co-expression experiments, secreted PCSK9 re-internalization assay, membrane-bound PCSK9 chimera constructs, lysosomal inhibitor studies, immunoblotting The Journal of biological chemistry High 18039658
2007 ApoER2 in Sertoli cells is a selenoprotein P (Sepp1) receptor that mediates receptor-dependent uptake of selenium into the testis; co-immunoprecipitation confirmed ApoER2-Sepp1 interaction; ApoER2 knockout mice have sharply reduced testis selenium and identical sperm defects as Sepp1 knockout mice Sepp1 affinity chromatography + mass spectrometry, co-immunoprecipitation, in situ hybridization, selenium measurement in ApoER2-/- mice, immunocytochemistry The Journal of biological chemistry High 17314095
2010 The E3 ubiquitin ligase IDOL induces ubiquitination of ApoER2 (and VLDLR) on their cytoplasmic tails, leading to their lysosomal degradation; LXR activation increases IDOL expression and decreases ApoER2/VLDLR levels; reduced IDOL-dependent ApoER2 levels decrease Reelin-induced Dab1 phosphorylation Ubiquitination assays, immunoblotting, siRNA knockdown, pharmacological LXR activation in mice, Dab1 phosphorylation assay The Journal of biological chemistry High 20427281
2012 ApoE-secreted by melanoma cells suppresses metastatic endothelial recruitment by engaging endothelial cell LRP8 receptors; miR-1908, miR-199a-5p, and miR-199a-3p convergently target ApoE, and their inhibition suppresses LRP8-mediated angiogenesis In vivo selection, locked nucleic acid (LNA) inhibition, cancer cell-endothelial co-culture assays, receptor-specific functional studies Cell Medium 23142051
2008 Activated protein C (APC) binds directly to ApoER2 (LRP8) with ~30 nM affinity (surface plasmon resonance) and signals via Dab1 Tyr-220 phosphorylation, followed by PI3K/Akt activation and GSK3β Ser-9 phosphorylation; siRNA knockdown of ApoER2 ablates APC-induced Dab1 phosphorylation Surface plasmon resonance, siRNA knockdown, phospho-specific immunoblotting, kinase inhibitors, receptor-associated protein (RAP) competition Proceedings of the National Academy of Sciences of the United States of America High 19116273
2010 In antiphospholipid syndrome, aPL antibodies bind β2GPI which dimerizes and engages ApoER2 on endothelial cells; this activates PP2A which dephosphorylates eNOS at Ser1179, suppressing NO production; ApoER2-/- mice are protected from aPL-induced thrombosis and leukocyte-endothelial adhesion Endothelial cell culture, RAP competition, ApoER2 knockout mice, eNOS phosphorylation immunoblotting, PP2A activity assays, intravital microscopy The Journal of clinical investigation High 21123944
2018 In endothelial cells, the ApoER2 cytoplasmic tail serves as a scaffold for aPL-induced assembly of heterotrimeric PP2A: Dab2 recruits to the NPXY motif and promotes L309 methylation (activation) of PP2A catalytic subunit via LCMT-1; SHC1 recruits scaffolding and regulatory PP2A subunits to the proline-rich C-terminus, mediating dephosphorylation of Akt and eNOS Co-immunoprecipitation, domain-specific mutants, siRNA knockdown, endothelial cell signaling assays, in vivo thrombosis model Blood High 29500169
2005 F-spondin interacts with ApoER2 through F-spondin's thrombospondin domain and ApoER2's ligand-binding domain (co-immunoprecipitation); F-spondin increases surface expression of APP and ApoER2, and shifts APP processing away from amyloidogenic β-secretase cleavage; this requires the ApoER2 receptor (blocked by RAP) Co-immunoprecipitation, surface biotinylation, APP CTF measurement, Aβ ELISA, primary neurons Molecular and cellular biology Medium 16227578
2006 FE65 adaptor protein interacts with ApoER2 via its N-terminal PTB domain, bridges a complex with APP, increases surface expression of ApoER2, and affects proteolytic processing of both ApoER2 and APP (increasing secreted forms while decreasing Aβ); both PTB domains of FE65 are required for full effect Co-immunoprecipitation in COS7 cells, surface biotinylation, CTF/secreted protein immunoblotting, Aβ measurement The Journal of biological chemistry Medium 16638748
2005 ApoER2 is endocytosed via a clathrin-mediated pathway dependent on the cytoplasmic FxNPXY motif and the adaptor protein Dab2; dominant-negative eps15 and Dab2 reduce ApoER2 internalization; caveolar/raft pathway is not required despite ApoER2 association with rafts Endocytosis assays, dominant-negative constructs (eps15, Dab2), nystatin treatment (caveolar inhibition), FxNPXY mutant analysis Traffic (Copenhagen, Denmark) High 16101684
2007 ApoER2 (but not VLDLR) controls migration of late-generated neocortical neurons; fate mapping in single and double receptor knockout mice shows VLDLR mediates a stop signal for migrating neurons while ApoER2 is essential for migration of late-born neurons BrdU fate mapping, layer-specific marker immunostaining, single and double receptor knockout mice Development (Cambridge, England) High 17913789
2009 ApoER2 sorting to lipid raft domains (vs. VLDLR in non-raft domains) determines receptor fate upon Reelin stimulation: raft-associated ApoER2 produces specific receptor fragments and undergoes lysosomal degradation after Reelin binding; non-raft VLDLR internalizes Reelin for degradation without significant receptor degradation Chimeric receptor panel, lipid raft fractionation, endocytosis assays, receptor fragment tracking The Journal of biological chemistry High 19948739
2008 Thrombospondin-1 (THBS-1) is a novel physiological ligand for ApoER2 and VLDLR; it binds both receptors and induces Dab1 phosphorylation but (unlike Reelin) does not induce Dab1 degradation or Akt phosphorylation; THBS-1 stabilizes neuronal precursor chains in rostral migratory stream independently of Reelin Ligand binding assays, Dab1 phosphorylation immunoblotting, SVZ explant chain formation assays, THBS-1 knockout mice analysis The EMBO journal High 18946489
2013 Clusterin binds to ApoER2 and VLDLR, is internalized by receptor-expressing cells, and triggers Reelin-like signaling: inducing Dab1 phosphorylation, PI3K/Akt activation, and n-cofilin activation; clusterin blockade impairs neuroblast chain formation in SVZ explants Binding/internalization assays, Dab1 phosphorylation immunoblotting, Akt phosphorylation, SVZ explant assays The Journal of biological chemistry Medium 24381170
2021 The E2-E1 glycoproteins of multiple alphaviruses (Semliki forest virus, EEEV, Sindbis) bind to the ligand-binding domains of ApoER2 (and VLDLR), mediating viral attachment and internalization; a VLDLR LBD-Fc fusion protein blocks alphavirus infection in neurons and protects mice from lethal SFV challenge CRISPR knockout screens, virus-like particle internalization assays, neutralization with LBD-Fc fusion protein, in vivo mouse challenge model Nature High 34929721
2007 ApoER2 physically interacts with APP and increases cell surface APP levels and APP association with lipid rafts by decreasing APP internalization rate; ApoER2 expression also increases γ-secretase activity and Aβ production; the ApoER2 NPxY motif is required for increased Aβ production Co-immunoprecipitation, surface biotinylation, APP internalization rate measurement, lipid raft fractionation, γ-secretase activity assay, Aβ ELISA, NPxY mutant analysis Molecular neurodegeneration Medium 17620134
2012 LRP8 positively regulates canonical Wnt/β-catenin signaling: ectopic LRP8 expression increases Wnt-induced β-catenin accumulation and transcriptional responses; LRP8 knockdown decreases β-catenin levels and suppresses Wnt target gene (Axin2) transcription; LRP8 depletion impairs osteoblast differentiation and mineralization siRNA knockdown, Wnt transcriptional reporter assay, β-catenin immunoblotting, Axin2 RT-PCR, osteoblast differentiation assay (KS483 cells), mineralization assay Journal of bone and mineral research Medium 22589174
2009 Factor XI (FXI) is identified as a ligand for platelet ApoER2; platelet adhesion to immobilized FXI is blocked by RAP, soluble recombinant ApoER2, or ApoER2 LDL-binding domains 1-2; ApoER2-deficient murine platelets fail to adhere to FXI; soluble FXI binds immobilized ApoER2 with ~61 nM affinity Platelet adhesion assay, RAP competition, soluble receptor domain competition, ApoER2 knockout mouse platelets, surface plasmon resonance Arteriosclerosis, thrombosis, and vascular biology High 19661487
2005 β2-glycoprotein I (β2GPI) domain V contains the binding site for ApoER2 on platelets; deletion of domain V abrogates β2GPI interaction with ApoER2 and platelet activation on collagen; domains I and II are dispensable for ApoER2 interaction Domain deletion mutants of β2GPI, immunoprecipitation with platelet ApoER2, platelet adhesion assay, whole blood flow assay The Journal of biological chemistry Medium 16091370
2015 Reelin binding to LRP8 triggers γ-secretase-dependent cleavage of LRP8, releasing its intracellular domain (ICD) which participates in a synapse-to-nucleus pathway to activate neuronal enhancers (LRN enhancers) governing synaptic plasticity genes; LRP8 ICD serves as a nuclear signal for chromatin remodeling during memory formation Chromatin immunoprecipitation (ChIP), enhancer profiling, γ-secretase inhibition, LRP8 knockdown, in vivo memory behavioral assays Neuron High 25892301
2013 Presenilin-1 (γ-secretase) processes ApoER2 sequentially (α- then γ-secretase), producing an intracellular C-terminal fragment (ICD); this ApoER2-ICD binds to the RELN promoter and suppresses reelin expression at the transcriptional level; PS1 conditional knockout mice show increased ApoER2 and reelin protein PS1 conditional knockout mice, γ-secretase inhibitor treatment, luciferase reporter assay, nuclear fractionation, chromatin immunoprecipitation (ChIP) FASEB journal High 24344333
2014 Sorting nexin 17 (SNX17) interacts with the NPxY endocytosis motif of ApoER2 via SNX17's FERM domain (GST pull-down, co-immunoprecipitation) and promotes ApoER2 recycling from early to recycling endosomes without affecting endocytic rate; SNX17 knockdown increases Reelin-induced ApoER2 degradation and impairs dendritic development and Reelin signaling in neurons GST pull-down, co-immunoprecipitation, endosomal trafficking assays, SNX17 siRNA knockdown, dendritic morphology analysis, Reelin-Dab1 phosphorylation assay PloS one Medium 24705369
2014 Differential splicing (exon 16 encoding O-linked sugar domain) and glycosylation of ApoER2 alters its extracellular cleavage, γ-secretase-dependent ICD release, synaptic abundance, spine density, and fear memory; OLS-deficient ApoER2 has reduced ectodomain shedding preventing ICD release Splice variant knock-in mice, electrophysiology (LTP), spine density analysis, behavioral testing (Morris water maze, fear conditioning), biochemical cleavage assays Science signaling High 25429077
2016 An antisense oligonucleotide (ASO) that increases ApoER2 exon 19 splicing corrects deregulated ApoER2 splicing in AD mouse brain, improving synaptic function and learning/memory; exon 19 splicing is deregulated in human AD brain postmortem ASO treatment in transgenic AD mice, LTP electrophysiology, behavioral testing (learning and memory), RT-PCR splice analysis in human postmortem brain EMBO molecular medicine Medium 26902204
2014 ApoE3 binding to ApoER2 on endothelial cells stimulates eNOS and endothelial cell migration, and attenuates monocyte-endothelial adhesion; ApoE4 (due to its N-to-C terminal interaction) does not stimulate eNOS and acts as dominant-negative antagonist of ApoE3/ApoER2 actions; ApoER2-R952Q is a loss-of-function receptor variant in endothelium eNOS activity assays, endothelial cell migration assays, ApoER2-/- mice, adenoviral ApoE3/E4 expression, carotid reendothelialization model, neointima formation model Proceedings of the National Academy of Sciences of the United States of America High 25197062
2009 Differential functions of ApoER2 intracellular signaling motifs and selenium uptake can be dissociated: knock-in mice with disrupted signaling motifs in the Apoer2 cytoplasmic domain maintain normal selenium in brain and testis, confirming that neurological defects in signaling-impaired mice are due to disrupted Reelin signaling, not selenium deficiency Knock-in mice (cytoplasmic domain signaling motif mutations), selenium measurement in tissues, sperm motility analysis Biological chemistry High 19007311
2012 ApoER2 mediates selenium uptake from selenoprotein P (Sepp1) in L8 myoblast cells via an endocytosis mechanism requiring heparin sulfate proteoglycan binding and the selenium-rich C-terminal domain of Sepp1; siRNA knockdown of ApoER2 (but not LRP1) inhibits 75Se uptake; lysosome acidification is required for Sepp1 digestion and selenium utilization Sepp1 affinity column + mass spectrometry, siRNA knockdown, 75Se-labeled Sepp1 uptake assay, lysosomal acidification inhibitors, heparin competition The Journal of biological chemistry High 22761431
2017 Crystal structure of the full-length ApoER2 ectodomain complexed with a signaling-competent Reelin fragment reveals an intermediate contracted-open conformation distinct from ligand-unbound LDLR; an auxiliary low-affinity binding interface is identified; pH-dependent weakening of this interface during endocytosis destabilizes the complex for ligand release X-ray crystallography, mutagenesis of binding interfaces, pH-dependent binding assays EMBO reports High 28446613
2015 ApoER2 and Reelin are expressed in peripheral nerve and regulate Schwann cell migration by activating the Rac1 GEF Tiam1; Reelin induces Rac1 activation at the leading edge of SCs (FRET assay); Tiam1 and PAR3 are required for Reelin-induced SC migration; PAR3 binds preferentially to the full-length ApoER2 cytoplasmic tail containing the exon 19-encoded proline-rich insert FRET-based Rac1 activation assay, siRNA knockdown of Tiam1/PAR3, sciatic nerve injury model, ApoER2 domain-specific binding assays Molecular and cellular neurosciences Medium 26386179
2017 GRIP1 binds ApoER2 and bridges a complex including ApoER2, ephrinB2, and AMPA receptors at the postsynapse; neuronal activity induces ephrinB2 Ser-9 phosphorylation which stabilizes the complex; mutation of ephrinB2 Ser-9 disrupts complex formation, abolishes ApoER2 downstream signaling, and impairs activity-induced AMPA receptor insertion and LTP Co-immunoprecipitation, phospho-mutant knock-in mice, compound genetics, LTP electrophysiology, AMPA receptor surface insertion assays Cell reports High 28978486
2017 The E3 ubiquitin ligase IDOL determines synaptic ApoER2 protein levels in response to neuronal activation; IDOL-dependent changes in ApoER2 regulate dendritic spine morphogenesis, filopodia initiation, synapse maturation, and LTP; IDOL-deficient mice show impaired experience-dependent synaptic remodeling and spatial/associative learning IDOL knockout mice, LTP electrophysiology in slices and primary neurons, dendritic spine imaging, barrel cortex plasticity assay, behavioral tests eLife High 28891791
2019 ApoER2 interacts with the catalytic subunit of PP2A (co-immunoprecipitation); in the absence of ApoER2, PP2A-C fails to interact with CDC20, resulting in inactive anaphase-promoting complex (APC/CDC20), cell cycle arrest at metaphase/anaphase, impaired cytokinesis, and premature smooth muscle cell senescence Co-immunoprecipitation, cell cycle protein immunoblotting, β-galactosidase senescence assay, p16INK4a immunofluorescence, multinucleated cell counting, Lrp8-/- mouse vascular injury model Arteriosclerosis, thrombosis, and vascular biology Medium 31412739
2019 SFRS11 RNA-binding protein directly binds LRP8 mRNA 3' UTR, stabilizing it; SFRS11 deficiency in the prefrontal cortex reduces LRP8 and apoE mRNA levels, activates JNK signaling, and causes learning/memory deficits; restoration of LRP8 and apoE reduces JNK activation and rescues aging-like phenotypes RNA immunoprecipitation (RIP), 3' UTR binding assay, SFRS11 knockdown in PFC, JNK signaling immunoblotting, behavioral tests Cell reports Medium 31269452
2023 LRP8 is identified as a CRISPR-activation screen hit protecting MYCN-amplified neuroblastoma from ferroptosis; LRP8 deletion causes ferroptosis by reducing selenoprotein P (SELENOP) uptake, insufficient selenocysteine supply for GPX4 translation; this is caused by low expression of alternative selenium uptake pathways (system Xc-) CRISPR-activation screen, LRP8 knockout (constitutive and inducible), xenograft models, selenoprotein/GPX4 immunoblotting, ferroptosis cell death assays EMBO molecular medicine High 37435859
2025 LRP8 is identified as a receptor for tick-borne encephalitis virus (TBEV) by genome-scale CRISPR-Cas9 screen; LRP8 binds directly to TBEV E glycoprotein and mediates viral attachment and internalization; LRP8 downregulation reduces TBEV infection; an LRP8-based soluble decoy blocks TBEV infection in human cell lines, neuronal cells, and protects mice from lethal TBEV challenge Genome-scale CRISPR-Cas9 screen, LRP8 overexpression/knockdown infection assays, direct binding assay (E glycoprotein), LRP8-based decoy receptor, in vivo mouse challenge Nature High 40993380
2019 In the off-state, ApoER2 and VLDLR form homo- or hetero-oligomers; full-length Reelin binding rearranges ApoER2 homo-oligomers into higher-order receptor clusters, leading to Dab1 phosphorylation; the Reelin central fragment does not increase cluster size or induce Dab1 phosphorylation but can induce hetero-oligomerization and cell shape changes via an alternative Dab1-independent mechanism Time-resolved anisotropy, fluorescence lifetime imaging microscopy (FLIM), FRET-based receptor oligomerization analysis in HEK293 cells Frontiers in molecular neuroscience Medium 30873003
2014 Neurotrophins regulate ApoER2 proteolysis: TrkA activation by NGF in PC12 cells induces ApoER2 ectodomain shedding (metalloproteinase-dependent); TrkB activation by BDNF similarly induces ApoER2 proteolysis in cortical neurons; this effect is independent of MAPK and PI3K activity Pharmacological TrkA/TrkB activation, metalloproteinase inhibitors, MAPK/PI3K inhibitors, ApoER2 shedding immunoblotting, primary cortical neurons BMC neuroscience Medium 25233900
2023 A high-affinity ApoER2 variant in Jurkat cells (with highly glycosylated O-linked sugar domain, Kd ~0.67 nM) mediates selenium transport from selenoprotein P (SeP) via a Sec lyase-independent mechanism requiring vesicle acidification; in contrast, low-affinity ApoER2 variants use a Sec lyase-dependent lysosomal degradation mechanism Binding affinity measurements (Kd determination), siRNA knockdown, Sec lyase inhibitor, lysosomal acidification inhibitors, 75Se uptake assay The Journal of biological chemistry Medium 37406814
2009 Splice variants of ApoER2 differ in ligand-binding domain composition: ApoER2-LA1237 binds Reelin central fragment more strongly than the RR8-containing fragment, whereas ApoER2-LA12378 binds comparably to all Reelin fragments lacking the C-terminal region; LA8 of ApoER2 and Reelin repeat 8 interfere with central fragment-ApoER2 binding Quantitative binding assays with purified Reelin fragments and ApoER2 variants, monoclonal antibody specific for LA12378 isoform, in situ expression analysis Neuroscience research Medium 19167437
2022 Human APOER2 isoforms lacking exons 5-8 (Δex5-8) generate the highest CTF amounts and those lacking exons 4-6 (Δex4-6) the lowest in response to APOE, correlating with ICD-mediated transcriptional activation; Apoer2 knockout neurons show decreased miniature excitatory event frequency, restored by lentiviral APOER2-FL or Δex4-6 but not Δex5-8 isoform Gene-specific long-read sequencing (25 isoform identification), CTF immunoblotting, ICD transcriptional reporter assay, miniature excitatory event recording in Apoer2-KO neurons, lentiviral rescue The Journal of neuroscience Medium 35414534
2013 CIN85 (multi-adaptor protein) colocalizes with ApoER2 in neurons in a Dab1-mediated manner; Reelin stimulation increases CIN85-ApoER2 colocalization and recruits CIN85 from plasma membrane domains to EEA1-positive early endosomes; Tyr phosphorylation of Dab1 strengthens CIN85 binding Co-immunoprecipitation, immunofluorescence colocalization, Reelin stimulation assay, early endosome marker co-staining Genes to cells Medium 23506116
2008 LRP8-deficient mice show reduced platelet activation in response to ADP or thrombin and prolonged carotid artery occlusion time (in vivo thrombosis); lipidated apoE3 inhibits platelet activation in a dose-dependent and largely LRP8-dependent manner; LRP8 function in thrombosis is partly apoE-independent Flow cytometry, aggregometry, intravital microscopy (carotid FeCl3 injury), tail bleeding assay, LRP8-/- and LRP8+/- mice Thrombosis research Medium 18706682
2016 The ApoER2/Dab1 interaction with PSD95 maintains stable dendritic architecture in mature hippocampal neurons; expression of a tailless ApoER2 mutant (unable to interact with PSD95) increases dendritogenesis and reduces spine density in mature neurons; interference reduces synaptic PSD95 and leads to synaptic re-insertion of NR2B-containing NMDARs Mutant ApoER2 (tailless) overexpression in mature hippocampal neurons, dendritic morphology analysis (in vitro and in vivo), PSD95 immunofluorescence, NMDAR subunit analysis Journal of cellular physiology Medium 27653801
2021 Protein phosphatase 2A (PP2A) activation via ApoER2 in trophoblasts drives preeclampsia in a mouse model of antiphospholipid syndrome, extending the apoER2-PP2A signaling axis to placental biology Mouse model of APS-related preeclampsia, ApoER2-specific genetic and pharmacological interventions Circulation research Medium 34404233

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 The proprotein convertase PCSK9 induces the degradation of low density lipoprotein receptor (LDLR) and its closest family members VLDLR and ApoER2. The Journal of biological chemistry 394 18039658
2005 Modulation of synaptic plasticity and memory by Reelin involves differential splicing of the lipoprotein receptor Apoer2. Neuron 382 16102539
2012 Convergent multi-miRNA targeting of ApoE drives LRP1/LRP8-dependent melanoma metastasis and angiogenesis. Cell 344 23142051
2004 Reelin promotes hippocampal dendrite development through the VLDLR/ApoER2-Dab1 pathway. Neuron 313 14715136
2000 The reelin receptor ApoER2 recruits JNK-interacting proteins-1 and -2. The Journal of biological chemistry 214 10827199
2007 Apolipoprotein E receptor-2 (ApoER2) mediates selenium uptake from selenoprotein P by the mouse testis. The Journal of biological chemistry 182 17314095
2010 Antiphospholipid antibodies promote leukocyte-endothelial cell adhesion and thrombosis in mice by antagonizing eNOS via β2GPI and apoER2. The Journal of clinical investigation 160 21123944
2007 Divergent roles of ApoER2 and Vldlr in the migration of cortical neurons. Development (Cambridge, England) 134 17913789
2015 LRP8-Reelin-Regulated Neuronal Enhancer Signature Underlying Learning and Memory Formation. Neuron 131 25892301
2012 PCSK9 regulates neuronal apoptosis by adjusting ApoER2 levels and signaling. Cellular and molecular life sciences : CMLS 118 22481440
2010 The E3 ubiquitin ligase IDOL induces the degradation of the low density lipoprotein receptor family members VLDLR and ApoER2. The Journal of biological chemistry 116 20427281
2021 VLDLR and ApoER2 are receptors for multiple alphaviruses. Nature 105 34929721
2005 F-spondin interaction with the apolipoprotein E receptor ApoEr2 affects processing of amyloid precursor protein. Molecular and cellular biology 102 16227578
2008 Activated protein C ligation of ApoER2 (LRP8) causes Dab1-dependent signaling in U937 cells. Proceedings of the National Academy of Sciences of the United States of America 98 19116273
2016 Therapeutic correction of ApoER2 splicing in Alzheimer's disease mice using antisense oligonucleotides. EMBO molecular medicine 94 26902204
2003 Binding of purified Reelin to ApoER2 and VLDLR mediates tyrosine phosphorylation of Disabled-1. Brain research. Molecular brain research 88 12670700
1999 Identification and characterization of LRP8 (apoER2) in human blood platelets. Journal of lipid research 88 10508213
2008 Thrombospondin-1 binds to ApoER2 and VLDL receptor and functions in postnatal neuronal migration. The EMBO journal 86 18946489
2003 Malformation of the radial glial scaffold in the dentate gyrus of reeler mice, scrambler mice, and ApoER2/VLDLR-deficient mice. The Journal of comparative neurology 86 12687696
2013 Clusterin is a ligand for apolipoprotein E receptor 2 (ApoER2) and very low density lipoprotein receptor (VLDLR) and signals via the Reelin-signaling pathway. The Journal of biological chemistry 81 24381170
2007 An LRP8 variant is associated with familial and premature coronary artery disease and myocardial infarction. American journal of human genetics 77 17847002
2017 The ApoE receptors Vldlr and Apoer2 in central nervous system function and disease. Journal of lipid research 74 28292942
2011 Similarities and differences in structure, expression, and functions of VLDLR and ApoER2. Molecular neurodegeneration 72 21554715
2002 Dentate granule cells in reeler mutants and VLDLR and ApoER2 knockout mice. Experimental neurology 72 12093079
2018 The Reelin Receptors Apolipoprotein E receptor 2 (ApoER2) and VLDL Receptor. International journal of molecular sciences 71 30304853
2003 Localization of ApoER2, VLDLR and Dab1 in radial glia: groundwork for a new model of reelin action during cortical development. Brain research. Developmental brain research 68 12586425
2018 Antiphospholipid antibodies induce thrombosis by PP2A activation via apoER2-Dab2-SHC1 complex formation in endothelium. Blood 65 29500169
2007 ApoER2 expression increases Abeta production while decreasing Amyloid Precursor Protein (APP) endocytosis: Possible role in the partitioning of APP into lipid rafts and in the regulation of gamma-secretase activity. Molecular neurodegeneration 65 17620134
2006 FE65 interaction with the ApoE receptor ApoEr2. The Journal of biological chemistry 64 16638748
2005 ApoER2 is endocytosed by a clathrin-mediated process involving the adaptor protein Dab2 independent of its Rafts' association. Traffic (Copenhagen, Denmark) 62 16101684
2023 LRP8-mediated selenocysteine uptake is a targetable vulnerability in MYCN-amplified neuroblastoma. EMBO molecular medicine 61 37435859
2009 Differential functions of ApoER2 and very low density lipoprotein receptor in Reelin signaling depend on differential sorting of the receptors. The Journal of biological chemistry 59 19948739
2014 Genetic variants of ApoE and ApoER2 differentially modulate endothelial function. Proceedings of the National Academy of Sciences of the United States of America 56 25197062
2012 LRP8 mediates Wnt/β-catenin signaling and controls osteoblast differentiation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 56 22589174
2009 Identification of coagulation factor XI as a ligand for platelet apolipoprotein E receptor 2 (ApoER2). Arteriosclerosis, thrombosis, and vascular biology 52 19661487
2007 ApoER2/VLDL receptor and Dab1 in the rostral migratory stream function in postnatal neuronal migration independently of Reelin. Proceedings of the National Academy of Sciences of the United States of America 52 17494763
2006 Polymorphism in maternal LRP8 gene is associated with fetal growth. American journal of human genetics 52 16642433
2005 The binding site in {beta}2-glycoprotein I for ApoER2' on platelets is located in domain V. The Journal of biological chemistry 52 16091370
2005 Apoer2: a reelin receptor to remember. Neuron 51 16102527
2014 Reelin receptors ApoER2 and VLDLR are expressed in distinct spatiotemporal patterns in developing mouse cerebral cortex. The Journal of comparative neurology 50 25308109
2012 Long isoform mouse selenoprotein P (Sepp1) supplies rat myoblast L8 cells with selenium via endocytosis mediated by heparin binding properties and apolipoprotein E receptor-2 (ApoER2). The Journal of biological chemistry 45 22761431
2014 Differential splicing and glycosylation of Apoer2 alters synaptic plasticity and fear learning. Science signaling 43 25429077
2018 Targeting LRP8 inhibits breast cancer stem cells in triple-negative breast cancer. Cancer letters 41 30227220
2007 Platelets express three different splice variants of ApoER2 that are all involved in signaling. Journal of thrombosis and haemostasis : JTH 40 17470198
2008 The Reelin receptors Apoer2 and Vldlr coordinate the patterning of Purkinje cell topography in the developing mouse cerebellum. PloS one 38 18301736
2014 Sorting nexin 17 regulates ApoER2 recycling and reelin signaling. PloS one 37 24705369
2013 ApoER2 processing by presenilin-1 modulates reelin expression. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 34 24344333
2016 Interfering of the Reelin/ApoER2/PSD95 Signaling Axis Reactivates Dendritogenesis of Mature Hippocampal Neurons. Journal of cellular physiology 32 27653801
2018 ApoER2 Controls Not Only Neuronal Migration in the Intermediate Zone But Also Termination of Migration in the Developing Cerebral Cortex. Cerebral cortex (New York, N.Y. : 1991) 30 27909010
2021 miR-30b-5p inhibits cancer progression and enhances cisplatin sensitivity in lung cancer through targeting LRP8. Apoptosis : an international journal on programmed cell death 29 33779882
2020 Genome-scale CRISPR activation screening identifies a role of LRP8 in Sorafenib resistance in Hepatocellular carcinoma. Biochemical and biophysical research communications 29 32312520
2019 ApoER2 (Apolipoprotein E Receptor-2) Deficiency Accelerates Smooth Muscle Cell Senescence via Cytokinesis Impairment and Promotes Fibrotic Neointima After Vascular Injury. Arteriosclerosis, thrombosis, and vascular biology 28 31412739
2019 SFRS11 Loss Leads to Aging-Associated Cognitive Decline by Modulating LRP8 and ApoE. Cell reports 27 31269452
2023 Role of Lipid Rafts on LRP8 Signaling Triggered by Anti-β2-GPI Antibodies in Endothelial Cells. Biomedicines 26 38137358
2018 Decreased generation of C-terminal fragments of ApoER2 and increased reelin expression in Alzheimer's disease. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 25 29442527
2017 The E3 ubiquitin ligase IDOL regulates synaptic ApoER2 levels and is important for plasticity and learning. eLife 25 28891791
2015 ApoER2 and Reelin are expressed in regenerating peripheral nerve and regulate Schwann cell migration by activating the Rac1 GEF protein, Tiam1. Molecular and cellular neurosciences 25 26386179
2014 Involvement of the Apoer2 and Lrp1 receptors in mediating the pathological effects of ApoE4 in vivo. Current Alzheimer research 25 24251389
2014 A novel molecular diagnostic marker for familial and early-onset coronary artery disease and myocardial infarction in the LRP8 gene. Circulation. Cardiovascular genetics 25 24867879
2013 ApoER2 and VLDLr are required for mediating reelin signalling pathway for normal migration and positioning of mesencephalic dopaminergic neurons. PloS one 25 23976984
2011 ApoER2 function in the establishment and maintenance of retinal synaptic connectivity. The Journal of neuroscience : the official journal of the Society for Neuroscience 25 21976526
2008 Deficiency of LRP8 in mice is associated with altered platelet function and prolonged time for in vivo thrombosis. Thrombosis research 25 18706682
2006 Low-density lipoprotein receptor-related protein 8 (LRP8) is upregulated in granulosa cells of bovine dominant follicle: molecular characterization and spatio-temporal expression studies. Biology of reproduction 22 17108332
2021 Molecular subtyping and functional validation of TTK, TPX2, UBE2C, and LRP8 in sensitivity of TNBC to paclitaxel. Molecular therapy. Methods & clinical development 21 33665229
2018 PCSK9: A potential regulator of apoE/apoER2 against inflammation in atherosclerosis? Clinica chimica acta; international journal of clinical chemistry 21 29727700
2018 LRP8 is overexpressed in estrogen-negative breast cancers and a potential target for these tumors. Cancer medicine 21 30575334
2009 Additive effect of LRP8/APOER2 R952Q variant to APOE epsilon2/epsilon3/epsilon4 genotype in modulating apolipoprotein E concentration and the risk of myocardial infarction: a case-control study. BMC medical genetics 21 19439088
2012 Reelin together with ApoER2 regulates interneuron migration in the olfactory bulb. PloS one 20 23209795
2007 The reelin receptors VLDLR and ApoER2 regulate sensorimotor gating in mice. Neuropharmacology 20 17261317
2017 GRIP1 Binds to ApoER2 and EphrinB2 to Induce Activity-Dependent AMPA Receptor Insertion at the Synapse. Cell reports 19 28978486
2009 Splicing variations in the ligand-binding domain of ApoER2 results in functional differences in the binding properties to Reelin. Neuroscience research 19 19167437
2023 An efficient selenium transport pathway of selenoprotein P utilizing a high-affinity ApoER2 receptor variant and being independent of selenocysteine lyase. The Journal of biological chemistry 18 37406814
2017 Structural basis for ligand capture and release by the endocytic receptor ApoER2. EMBO reports 18 28446613
2016 Presenilin 1 mutations influence processing and trafficking of the ApoE receptor apoER2. Neurobiology of aging 18 27810638
2015 Convergent Lines of Evidence Support LRP8 as a Susceptibility Gene for Psychosis. Molecular neurobiology 18 26637325
2009 Differential functions of the Apoer2 intracellular domain in selenium uptake and cell signaling. Biological chemistry 18 19007311
2009 Reelin and apolipoprotein E receptor 2 in the embryonic and mature brain: effects of an evolutionary change in the apoER2 gene. Proceedings. Biological sciences 18 19846452
2021 Protein Phosphatase 2A Activation Via ApoER2 in Trophoblasts Drives Preeclampsia in a Mouse Model of the Antiphospholipid Syndrome. Circulation research 16 34404233
2017 Clusterin signals via ApoER2/VLDLR and induces meiosis of male germ cells. American journal of translational research 16 28386352
2013 Contributions of VLDLR and LRP8 in the establishment of retinogeniculate projections. Neural development 16 23758727
2012 SeP, ApoER2 and megalin as necessary factors to maintain Se homeostasis in mammals. Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) 16 22683052
2005 The apoE receptor apoER2 is involved in the maintenance of efficient synaptic plasticity. Neurobiology of aging 16 15582748
2024 Enhanced LRP8 expression induced by Helicobacter pylori drives gastric cancer progression by facilitating β-Catenin nuclear translocation. Journal of advanced research 15 38609049
2023 ApoER2-Dab1 disruption as the origin of pTau-associated neurodegeneration in sporadic Alzheimer's disease. Acta neuropathologica communications 15 38093390
2019 Differential Action of Reelin on Oligomerization of ApoER2 and VLDL Receptor in HEK293 Cells Assessed by Time-Resolved Anisotropy and Fluorescence Lifetime Imaging Microscopy. Frontiers in molecular neuroscience 15 30873003
2019 miR-409-5p negatively regulates Wnt/Beta catenin signaling pathway by targeting Lrp-8. Journal of cellular physiology 15 31165485
2021 miR-362-3p suppresses ovarian cancer by inhibiting LRP8. Translational oncology 14 34839107
2019 Effect of Aluminum-Maltolate on the Content of Aβ Protein and the Expression of ApoER2, VLDLRs, and LRP1 in PC12-ApoE4 Cells. Neurotoxicity research 14 30649678
2017 Further evidence for the association between LRP8 and schizophrenia. Schizophrenia research 14 28495490
2013 Multi-allelic haplotype association identifies novel information different from single-SNP analysis: a new protective haplotype in the LRP8 gene is against familial and early-onset CAD and MI. Gene 14 23524007
2007 Altered performance of reelin-receptor ApoER2 deficient mice on spatial tasks using the Barnes maze. Behavioral neuroscience 13 17907841
2021 Coix lacryma-jobi Seed Oil Reduces Fat Accumulation in Nonalcoholic Fatty Liver Disease by Inhibiting the Activation of the p-AMPK/SePP1/apoER2 Pathway. Journal of oleo science 12 33840662
2020 Carnosic Acid Reverses the Inhibition of ApoE4 on Cell Surface Level of ApoER2 and Reelin Signaling Pathway. Journal of Alzheimer's disease : JAD 12 31796678
2020 LRP8 activates STAT3 to induce PD-L1 expression in osteosarcoma. Tumori 12 33054597
2022 Human APOER2 Isoforms Have Differential Cleavage Events and Synaptic Properties. The Journal of neuroscience : the official journal of the Society for Neuroscience 11 35414534
2012 Genetic variant R952Q in LRP8 is associated with increased plasma triglyceride levels in patients with early-onset CAD and MI. Annals of human genetics 11 22404453
2025 LRP8 is a receptor for tick-borne encephalitis virus. Nature 10 40993380
2022 Single molecule, long-read Apoer2 sequencing identifies conserved and species-specific splicing patterns. Genomics 10 35192893
2014 Neurotrophins regulate ApoER2 proteolysis through activation of the Trk signaling pathway. BMC neuroscience 10 25233900
2013 Dab1-mediated colocalization of multi-adaptor protein CIN85 with Reelin receptors, ApoER2 and VLDLR, in neurons. Genes to cells : devoted to molecular & cellular mechanisms 10 23506116