Affinage

Showing LRP8APOER2 is a alias.

LRP8

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

Length
963 aa
Mass
105.6 kDa
Annotated
2026-06-10
100 papers in source corpus 46 papers cited in narrative 46 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LRP8/ApoER2 is a multifunctional LDL-receptor-family transmembrane protein that operates simultaneously as a signal transducer, endocytic/recycling receptor, and selenium-uptake receptor across the nervous, vascular, and reproductive systems (PMID:12670700, PMID:17314095, PMID:25892301). In neurons it binds Reelin with high affinity and, upon ligand-induced clustering of pre-formed homo-oligomers, drives tyrosine phosphorylation of the adaptor Dab1 and downstream PI3K/Akt signaling, controlling neuronal precursor migration, dendritic and synaptic morphogenesis, LTP, and memory (PMID:12670700, PMID:30873003, PMID:17494763, PMID:28891791); structural work shows the receptor ectodomain adopts a contracted-open conformation with a pH-sensitive auxiliary interface that primes ligand release during endocytosis (PMID:28446613). Beyond Reelin, ApoER2 is engaged by a broad ligand repertoire — thrombospondin-1, clusterin, F-spondin, ApoE, activated protein C, factor XI, β2-glycoprotein I, and selenoprotein P — that converge on Dab1 but produce distinct signaling outputs and receptor fates (PMID:18946489, PMID:24381170, PMID:16227578, PMID:25197062, PMID:19116273, PMID:19661487, PMID:16091370, PMID:17314095). Signal output and trafficking are encoded in the cytoplasmic tail: an NPxY/FxNPXY motif mediates clathrin-dependent endocytosis through Dab2 and recycling through SNX17, while proline-rich and exon-19-encoded segments recruit JIP scaffolds and PAR3 (PMID:16101684, PMID:24705369, PMID:10827199, PMID:26386179). γ-Secretase/presenilin-1 cleavage releases a transcriptionally active intracellular domain that activates neuronal enhancers and represses the RELN promoter, and this processing is tuned by extensive alternative splicing of the ligand-binding repeats and O-linked sugar domain (PMID:25892301, PMID:24344333, PMID:25429077, PMID:35414534). Receptor abundance is set post-translationally by PCSK9-directed lysosomal degradation and IDOL-mediated ubiquitination, with PCSK9 promoting and IDOL controlling activity-dependent synaptic ApoER2 levels (PMID:18039658, PMID:22481440, PMID:20427281, PMID:28891791). In endothelium and trophoblasts, the apoER2 tail scaffolds a Dab2–SHC1–PP2A complex that dephosphorylates eNOS and Akt, mediating antiphospholipid-antibody-driven thrombosis and preeclampsia (PMID:29500169, PMID:21123944, PMID:34404233). ApoER2 also functions as the receptor for selenoprotein P-dependent selenium uptake required for spermatogenesis and for GPX4-dependent ferroptosis resistance in MYCN-amplified neuroblastoma, drives Wnt/β-catenin signaling in osteoblasts, and serves as an entry receptor for alphaviruses and tick-borne encephalitis virus (PMID:17314095, PMID:37435859, PMID:22589174, PMID:34929721, PMID:40993380).

Mechanistic history

Synthesis pass · year-by-year structured walk · 41 steps
  1. 2000 Medium

    Established that ApoER2 is not merely an endocytic receptor but a signaling platform, by showing it selectively assembles JNK-scaffold proteins distinguishing it from VLDLR.

    Evidence Co-IP, yeast two-hybrid, and domain mapping of ApoER2-JIP1/JIP2 interactions

    PMID:10827199

    Open questions at the time
    • Functional consequence of JIP/JNK assembly for neuronal signaling not measured in vivo
    • Does not address Reelin-dependence of complex formation
  2. 2003 High

    Resolved which receptors transduce the Reelin signal, demonstrating direct Reelin binding to ApoER2 and VLDLR drives Dab1 phosphorylation and that both are jointly required.

    Evidence Purified Reelin binding assays and Dab1 phosphorylation in receptor-null cortical neurons

    PMID:12670700

    Open questions at the time
    • Downstream effectors of Dab1 not delineated here
    • Did not address ligand-specific receptor fate
  3. 2005 High

    Connected ApoER2 to synaptic plasticity, showing it sits in postsynaptic densities, complexes with NMDA receptors, and requires an alternatively spliced exon to enhance LTP and memory.

    Evidence PSD fractionation, Co-IP, knock-in mice, LTP electrophysiology and behavior

    PMID:16102539

    Open questions at the time
    • Molecular mechanism linking exon-19 segment to NMDAR phosphorylation incompletely defined
    • Identity of the relevant kinase not established
  4. 2005 Medium

    Defined the endocytic machinery of ApoER2, mapping clathrin-mediated internalization to the cytoplasmic FxNPXY motif via the adaptor Dab2.

    Evidence Dominant-negative eps15/Dab2, clathrin inhibition, internalization and Co-IP assays

    PMID:16101684

    Open questions at the time
    • Recycling versus degradative sorting not resolved
    • In vivo relevance not tested
  5. 2007 High

    Identified ApoER2 as a selenium-uptake receptor, showing it binds selenoprotein P in Sertoli cells and is required for testis selenium and normal spermatogenesis.

    Evidence Sepp1 affinity chromatography/MS, Co-IP, ApoER2-knockout mice, selenium measurement

    PMID:17314095

    Open questions at the time
    • Intracellular fate of Sepp1-derived selenium not detailed
    • Whether signaling and uptake share receptor pools unresolved
  6. 2007 High

    Revealed post-translational control of receptor levels, showing PCSK9 targets ApoER2 to lysosomes in a catalysis-independent manner.

    Evidence Co-expression, secreted-protein re-internalization, catalytically inactive PCSK9, lysosomal targeting immunoblots

    PMID:18039658

    Open questions at the time
    • Physiological tissue context of PCSK9 regulation not addressed here
    • Binding interface on ApoER2 not mapped
  7. 2008 High

    Expanded the ApoER2 ligand repertoire and showed ligand-specific signaling outcomes, with thrombospondin-1 inducing Dab1 phosphorylation but not Akt activation or Dab1 degradation, and stabilizing migrating neuroblast chains.

    Evidence Ligand binding, Dab1 phospho-immunoblot, THBS-1 knockout mice, SVZ explants

    PMID:18946489

    Open questions at the time
    • Structural basis for differential signaling versus Reelin unknown
    • Receptor selectivity between ApoER2/VLDLR not dissected
  8. 2008 High

    Showed ApoER2 functions in Reelin-independent migration, with ApoER2/Dab1 required for SVZ-to-olfactory-bulb chain migration.

    Evidence Compound knockout mice, organotypic migration assay, neuroanatomy

    PMID:17494763

    Open questions at the time
    • Ligand driving Reelin-independent migration not identified in this study
    • Signaling pathway downstream not mapped
  9. 2008 High

    Demonstrated ApoER2 as a vascular/coagulation signaling receptor, showing high-affinity activated protein C binding selectively to ApoER2 drives Dab1/Akt/GSK3β phosphorylation via PI3K.

    Evidence SPR binding, siRNA knockdown, phospho-immunoblots, PI3K inhibition

    PMID:19116273

    Open questions at the time
    • In vivo vascular consequences not addressed in this study
    • Cell-type specificity of APC signaling not defined
  10. 2009 High

    Dissociated ApoER2's signaling and selenium-uptake functions, proving via cytoplasmic-domain knock-in mice that neurological defects arise from disrupted Reelin signaling, not impaired selenium uptake.

    Evidence Signaling-impaired cytoplasmic-domain knock-in mice with tissue selenium and neurological phenotyping

    PMID:19007311

    Open questions at the time
    • Extracellular determinants of selenium uptake not mapped here
    • Does not address overlap in other tissues
  11. 2009 Medium

    Showed alternative splicing of ligand-binding repeats tunes Reelin affinity, establishing receptor isoform diversity as a regulatory layer.

    Evidence Quantitative binding of Reelin fragments to LA-repeat splice variants, neuron signaling assays

    PMID:19167437

    Open questions at the time
    • In vivo significance of specific isoforms not tested
    • Single-lab binding analysis
  12. 2009 Medium

    Linked membrane microdomain sorting to divergent receptor fates, showing raft-resident ApoER2 generates fragments and is lysosomally degraded whereas VLDLR is not.

    Evidence Chimeric receptors, raft fractionation, Reelin endocytosis and degradation assays

    PMID:19948739

    Open questions at the time
    • Negative feedback consequences only inferred
    • Single-lab domain-swap approach
  13. 2010 High

    Identified IDOL-mediated ubiquitination as a second post-translational control of ApoER2/VLDLR levels linking LXR to Reelin signaling.

    Evidence Ubiquitination assays, LXR pharmacology in mice, Dab1 phospho-readouts

    PMID:20427281

    Open questions at the time
    • Neuronal physiological role addressed only later
    • Relative contribution of PCSK9 vs IDOL not compared
  14. 2010 High

    Defined the endothelial pathomechanism of antiphospholipid antibodies, showing ApoER2-dependent β2GPI-driven PP2A antagonism of eNOS underlies thrombosis.

    Evidence ApoER2-knockout mice, in vivo thrombosis, eNOS phospho-immunoblot, PP2A activity

    PMID:21123944

    Open questions at the time
    • Molecular architecture of the PP2A scaffold not yet resolved (later defined)
    • Other antibody targets not excluded
  15. 2012 Medium

    Extended ApoER2 ubiquitin/degradation regulation to neuronal survival, showing PCSK9 promotes apoptosis by lowering ApoER2 and its ERK/JNK signaling.

    Evidence RNAi knockdown, caspase/apoptosis assays, signaling inhibition in cerebellar granule neurons

    PMID:22481440

    Open questions at the time
    • Endogenous PCSK9 source in brain not defined
    • NMDAR-independence asserted but mechanism of ERK/JNK coupling unmapped
  16. 2012 Medium

    Placed ApoER2 in tumor-suppressive endothelial signaling, identifying it as the endothelial receptor for cancer-secreted ApoE that suppresses metastatic endothelial recruitment.

    Evidence In vivo selection, siRNA, miRNA inhibition, xenograft metastasis models

    PMID:23142051

    Open questions at the time
    • Downstream signaling from ApoE-ApoER2 not delineated here
    • Single-lab study
  17. 2012 Medium

    Connected ApoER2 to Wnt/β-catenin-driven osteoblast differentiation, broadening its developmental signaling roles.

    Evidence siRNA/overexpression, Wnt reporter, β-catenin immunoblot, osteoblast mineralization

    PMID:22589174

    Open questions at the time
    • Mechanism of Wnt-pathway coupling unknown
    • In vivo skeletal phenotype not shown
  18. 2012 High

    Refined selenium-uptake mechanism, showing ApoER2-mediated Sepp1 uptake requires heparan sulfate proteoglycans and that lysosomal acidification is needed for selenium utilization but not uptake.

    Evidence siRNA, 75Se uptake, affinity chromatography/MS, lysosomal inhibition in myoblasts

    PMID:22761431

    Open questions at the time
    • HSPG identity not specified
    • Generalizability across cell types only partly tested
  19. 2013 High

    Showed γ-secretase-generated ApoER2 CTF acts as a transcriptional repressor of RELN, establishing a feedback loop between receptor processing and ligand expression.

    Evidence PS1 conditional knockout mice, ChIP, luciferase reporter, nuclear fractionation

    PMID:24344333

    Open questions at the time
    • Cofactors enabling CTF promoter binding unidentified
    • Genomic breadth of CTF targets not mapped here
  20. 2013 Medium

    Added clusterin as a Reelin-mimetic ligand that triggers Dab1/PI3K/Akt/cofilin signaling and supports SVZ neuroblast chains.

    Evidence Binding/internalization, signaling immunoblots, SVZ explants with blocking antibody

    PMID:24381170

    Open questions at the time
    • Binding interface on ApoER2 not mapped
    • Single-lab functional study
  21. 2013 Medium

    Mapped Reelin-induced adaptor dynamics, showing Dab1 phosphorylation recruits CIN85 to ApoER2 and traffics it to early endosomes.

    Evidence Co-IP, immunofluorescence colocalization with endosomal markers, phospho-Dab1 binding

    PMID:23506116

    Open questions at the time
    • Functional output of CIN85 recruitment not defined
    • Single-lab imaging study
  22. 2014 Medium

    Identified SNX17 as a recycling factor that protects ApoER2 from Reelin-induced degradation and supports dendritic development.

    Evidence GST pull-down, Co-IP, recycling assay, siRNA, neuronal morphology, Dab1 phospho-assay

    PMID:24705369

    Open questions at the time
    • In vivo requirement not tested
    • Single-lab study
  23. 2014 High

    Defined ApoE-isoform-specific endothelial signaling and a human loss-of-function variant, showing ApoE3-ApoER2 stimulates eNOS and migration while ApoE4 antagonizes it and the R952Q variant impairs function.

    Evidence eNOS/migration/adhesion assays, ApoER2-knockout reendothelialization and neointima models, adenoviral apoE

    PMID:25197062

    Open questions at the time
    • Structural basis of ApoE3/E4 discrimination at receptor not resolved
    • Human variant studied functionally, not clinically
  24. 2014 Medium

    Showed neurotrophin signaling regulates ApoER2 proteolysis, with TrkA/TrkB activation inducing metalloproteinase-dependent shedding independent of MAPK/PI3K.

    Evidence TrkA/TrkB activation, metalloproteinase and pathway inhibitors, CTF immunoblot

    PMID:25233900

    Open questions at the time
    • Identity of the responsible sheddase not established
    • Downstream transcriptional consequence not measured
  25. 2014 High

    Established the O-linked sugar domain (exon 16) as a regulator of receptor cleavage and synaptic output, with its absence reducing cleavage and altering spine density and synaptic efficacy in vivo.

    Evidence Knock-in mice, cleavage assays, spine quantification, LTP electrophysiology, behavior

    PMID:25429077

    Open questions at the time
    • Mechanism by which cleavage controls synaptic strength not fully resolved
    • Sheddase responsible not identified here
  26. 2015 High

    Defined a synapse-to-nucleus pathway whereby Reelin-induced, γ-secretase-dependent ApoER2 ICD release activates neuronal enhancers governing memory.

    Evidence In vivo ChIP-seq, γ-secretase inhibition, ICD nuclear fractionation, behavior

    PMID:25892301

    Open questions at the time
    • Direct DNA-binding partners of the ICD not all identified
    • Distinction from CTF repressor role at RELN not reconciled
  27. 2015 Medium

    Extended ApoER2-Reelin signaling to peripheral nerve repair, showing the exon-19/proline-rich variant binds PAR3 and activates Rac1 via Tiam1 to drive Schwann cell migration.

    Evidence FRET Rac1 activation, Co-IP, siRNA, migration assay, nerve injury model

    PMID:26386179

    Open questions at the time
    • In vivo regeneration outcome not quantified
    • Single-lab study
  28. 2016 Medium

    Provided translational proof that correcting ApoER2 exon-19 splicing improves synaptic function and memory in AD mice and that this splicing is deregulated in AD patient brain.

    Evidence ASO treatment in AD mice, human postmortem splice analysis, electrophysiology, behavior

    PMID:26902204

    Open questions at the time
    • Mechanism linking exon-19 loss to AD pathology incompletely defined
    • Single-lab therapeutic study
  29. 2016 Medium

    Showed disease-linked presenilin-1 mutations disrupt ApoER2 processing and surface trafficking, connecting familial AD machinery to receptor biology.

    Evidence PS1 mutant cell lines, CTF immunoblot, surface biotinylation, γ-secretase inhibition

    PMID:27810638

    Open questions at the time
    • In vivo consequences of altered ApoER2 processing not tested
    • Single-lab cell study
  30. 2017 High

    Defined the activity-dependent control of synaptic ApoER2 by IDOL ubiquitination governing spine remodeling and LTP.

    Evidence IDOL-knockout neurons, spine imaging, LTP, barrel cortex plasticity, behavior

    PMID:28891791

    Open questions at the time
    • Signal that triggers IDOL action on ApoER2 not defined
    • Crosstalk with PCSK9 pathway not addressed
  31. 2017 High

    Identified GRIP1-bridged ApoER2-ephrinB2-AMPA receptor complexes required for activity-induced AMPA insertion and LTP.

    Evidence Co-IP, ephrinB2 Ser-9 knock-in mice, AMPA surface insertion, LTP

    PMID:28978486

    Open questions at the time
    • Upstream kinase for ephrinB2 Ser-9 not identified
    • Relationship to Reelin-Dab1 signaling not delineated
  32. 2017 High

    Resolved the structural basis of Reelin recognition and pH-triggered release, showing ApoER2 adopts a contracted-open conformation with an auxiliary low-affinity interface destabilized during endocytosis.

    Evidence X-ray crystallography of ectodomain-Reelin fragment complex with mutational and pH-dependent binding analysis

    PMID:28446613

    Open questions at the time
    • Structure of full-length signaling-competent cluster not solved
    • Conformations with other ligands unknown
  33. 2019 Medium

    Explained how ligand form dictates signaling, showing full-length Reelin rearranges pre-formed ApoER2 oligomers into higher-order clusters that trigger Dab1 phosphorylation whereas the central fragment does not.

    Evidence FLIM/FRET and fluorescence anisotropy of tagged receptors in HEK293 cells

    PMID:30873003

    Open questions at the time
    • Cluster stoichiometry in neurons not measured
    • Single-lab biophysical study
  34. 2019 Medium

    Linked ApoER2 to cell-cycle control in vascular smooth muscle, showing it is required for PP2A-CDC20 interaction, APC/C activity, and prevention of senescence.

    Evidence Co-IP of ApoER2 with PP2A-C/CDC20, cell-cycle immunoblots, senescence assays, Lrp8-knockout mice

    PMID:31412739

    Open questions at the time
    • Mechanism coupling a surface receptor to mitotic APC/C unclear
    • Single-lab study
  35. 2018 High

    Resolved the molecular architecture of the pathogenic endothelial PP2A scaffold, showing the apoER2 tail recruits Dab2 (promoting PP2A catalytic-subunit methylation) and SHC1 (recruiting the scaffolding subunit) to dephosphorylate Akt/eNOS and drive thrombosis.

    Evidence Domain-specific mutational Co-IP, PP2A activity, mouse thrombosis, ApoER2-knockout

    PMID:29500169

    Open questions at the time
    • How antibody engagement initiates assembly structurally undefined
    • Therapeutic targetability not tested
  36. 2021 Medium

    Extended the apoER2-PP2A pathomechanism to pregnancy, implicating trophoblast apoER2-PP2A signaling in antiphospholipid-driven preeclampsia.

    Evidence Mouse antiphospholipid syndrome model, trophoblast genetics, PP2A activity, preeclampsia readouts

    PMID:34404233

    Open questions at the time
    • Trophoblast-specific receptor partners not fully mapped
    • Single-lab in vivo study
  37. 2021 High

    Revealed an unexpected role as a viral entry receptor, showing alphavirus E2-E1 glycoproteins engage ApoER2/VLDLR ligand-binding domains to mediate infection.

    Evidence Ectopic expression entry assays, VLP internalization, LBD-Fc blocking, mouse challenge

    PMID:34929721

    Open questions at the time
    • Relative ApoER2 vs VLDLR contribution in vivo not separated
    • Tissue tropism determinants unclear
  38. 2022 Medium

    Showed human APOER2 isoform diversity tunes CTF/ICD generation and synaptic function, with specific repeat deletions altering transmission via Mint1-mediated ICD release.

    Evidence Sequencing of 25 human isoforms, CTF immunoblot, ICD fractionation, Mint1 assay, knockout-rescue, mEPSC recordings

    PMID:35414534

    Open questions at the time
    • In vivo prevalence of disease-relevant isoforms unknown
    • Single-lab study
  39. 2023 Medium

    Established a high-affinity O-glycosylated ApoER2 variant mediating selenocysteine-lyase-independent selenium transport, refining how isoforms determine selenium handling.

    Evidence Variant characterization, SeP binding affinity, siRNA, 75Se uptake, Sec lyase and acidification inhibition

    PMID:37406814

    Open questions at the time
    • Physiological tissues using this pathway not defined
    • Single-lab study
  40. 2023 High

    Identified ApoER2 as a ferroptosis-resistance determinant in cancer, showing LRP8-mediated SELENOP uptake supplies selenocysteine for GPX4 translation in MYCN-amplified neuroblastoma.

    Evidence CRISPR activation screen, constitutive/inducible LRP8 knockout in xenografts, ferroptosis and GPX4 assays

    PMID:37435859

    Open questions at the time
    • Generalizability beyond low-system-Xc- cancers limited
    • Targetability for therapy not tested
  41. 2025 High

    Identified ApoER2 as a receptor for tick-borne encephalitis virus, showing direct E-glycoprotein binding mediates attachment/internalization and a soluble decoy protects mice.

    Evidence Genome-scale CRISPR screen, overexpression/knockdown, direct binding, decoy in cells and mouse challenge

    PMID:40993380

    Open questions at the time
    • Contribution to neurotropism in vivo not dissected
    • Receptor usage relative to other flavivirus receptors unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single receptor coordinates its mutually exclusive roles — Reelin signaling, broad-ligand transduction, selenium transport, viral entry, and cytoplasmic PP2A/cell-cycle scaffolding — through isoform choice, glycosylation, microdomain sorting, and ubiquitin/protease control remains unresolved.
  • No unified model of how isoform/glycosylation states partition signaling vs transport functions
  • Structures of full-length signaling clusters and ligand-specific conformations lacking
  • Direct nuclear partners of the ICD/CTF incompletely identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0038024 cargo receptor activity 4 GO:0060089 molecular transducer activity 4 GO:0060090 molecular adaptor activity 4 GO:0001618 virus receptor activity 2 GO:0008289 lipid binding 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005886 plasma membrane 4 GO:0005634 nucleus 3 GO:0005764 lysosome 3 GO:0005768 endosome 3
Pathway
R-HSA-109582 Hemostasis 4 R-HSA-112316 Neuronal System 4 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-382551 Transport of small molecules 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-1266738 Developmental Biology 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-5357801 Programmed Cell Death 2
Complex memberships
APC/C-CDC20 (PP2A) mitotic complexApoER2-NMDA receptor postsynaptic complexApoER2-ephrinB2-AMPA receptor (GRIP1) complexapoER2-Dab2-SHC1-PP2A endothelial complex

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 ApoER2 is present in postsynaptic densities of excitatory synapses where it forms a functional complex with NMDA receptors. Reelin signaling through ApoER2 enhances LTP through a mechanism requiring amino acids encoded by an alternatively spliced exon (exon 19) in the intracellular domain, which is required for Reelin-induced tyrosine phosphorylation of NMDA receptor subunits. Co-immunoprecipitation, postsynaptic density fractionation, alternative splicing analysis, LTP electrophysiology, behavioral learning/memory tasks in knock-in mice Neuron High 16102539
2000 ApoER2, but not VLDLR, binds JNK-interacting proteins (JIP-1 and JIP-2), which act as molecular scaffolds for the JNK signaling pathway. The ApoER2 binding domain on JIP-2 does not overlap with binding sites for MLK3, MKK7, and JNK, allowing ApoER2 to assemble a multiprotein complex containing Disabled-1 and JIPs at the neuronal cell surface. Co-immunoprecipitation, yeast two-hybrid, domain mapping The Journal of biological chemistry Medium 10827199
2003 Purified Reelin binds directly to ApoER2 and VLDLR to induce tyrosine phosphorylation of Disabled-1 (Dab1). ApoER2 shows greater Reelin-binding affinity than VLDLR. Complete absence of both receptors abolishes Reelin-induced Dab1 phosphorylation in cortical neurons. Purified Reelin binding assay, Dab1 phosphorylation immunoblot, genetic knockout mice, cortical neuron cultures Brain research. Molecular brain research High 12670700
2007 PCSK9 induces degradation of ApoER2 (as well as LDLR and VLDLR) either via cellular co-expression or re-internalization of secreted PCSK9. This degradation does not require PCSK9 catalytic activity and is directed to late endosomes/lysosomes. Membrane-bound PCSK9 chimeras are more efficient at degrading ApoER2 than secreted PCSK9. Cell co-expression, secreted protein re-internalization, lysosomal targeting assays, catalytically inactive mutant PCSK9, immunoblotting The Journal of biological chemistry High 18039658
2007 ApoER2 mediates selenium uptake from selenoprotein P (Sepp1) in the mouse testis. Sertoli cells express ApoER2 as the Sepp1 receptor; apoER2-deficient males show sharply reduced testis selenium and identical sperm defects to Sepp1-deficient males. Co-immunoprecipitation confirmed ApoER2-Sepp1 interaction. Sepp1 affinity chromatography, mass spectrometry, co-immunoprecipitation, ApoER2 knockout mice, in situ hybridization, immunocytochemistry, selenium measurement The Journal of biological chemistry High 17314095
2008 ApoER2 and Dab1 are required for postnatal chain migration of neuronal precursors from the subventricular zone to the olfactory bulb in a Reelin-independent manner. Mice lacking both ApoER2 and VLDLR, or Dab1, showed severely compromised chain formation and virtual absence of the rostral migratory stream. Genetic knockout mice, organotypic migration assay, immunohistochemistry, neuroanatomical analysis Proceedings of the National Academy of Sciences of the United States of America High 17494763
2008 Thrombospondin-1 (THBS-1) is a novel physiological ligand for ApoER2 and VLDLR. THBS-1 binds ApoER2 and VLDLR and induces phosphorylation of Dab1 but, unlike Reelin, does not induce Dab1 degradation or Akt phosphorylation. THBS-1 stabilizes neuronal precursor chains in the rostral migratory stream. Ligand binding assay, Dab1 phosphorylation immunoblot, THBS-1 knockout mice, subventricular zone explant cultures The EMBO journal High 18946489
2005 F-spondin interacts with ApoER2 through its thrombospondin domain binding to the ApoER2 ligand-binding domain. Full-length F-spondin increases ApoER2-APP co-immunoprecipitation, increases surface expression of both, promotes cleavage of APP and ApoER2, and decreases Aβ production in a RAP-inhibitable manner. Co-immunoprecipitation, surface biotinylation, RAP-inhibition assay, cell transfection, primary neuron cultures Molecular and cellular biology Medium 16227578
2008 Activated protein C (APC) binds directly and with high affinity (Kd ~30 nM) to ApoER2 (but not VLDLR) via a surface plasmon resonance-measured interaction. APC ligation of ApoER2 induces rapid phosphorylation of Dab1 Tyr-220 and Akt Ser-473, with downstream GSK3β Ser-9 phosphorylation via PI3K. siRNA knockdown of ApoER2 abolishes APC-induced Dab1 phosphorylation. Surface plasmon resonance, siRNA knockdown, phospho-specific immunoblotting, PI3K inhibitor, RAP blocking Proceedings of the National Academy of Sciences of the United States of America High 19116273
2010 The E3 ubiquitin ligase IDOL induces ubiquitination of ApoER2 and VLDLR on their cytoplasmic tails, leading to their degradation. LXR activation increases IDOL expression and decreases VLDLR levels in vivo. LXR activation reduces Reelin binding to VLDLR and Dab1 phosphorylation, functionally linking LXR and Reelin signaling. Ubiquitination assay, cell overexpression, siRNA knockdown, pharmacological LXR activation in mice, Dab1 phosphorylation immunoblot The Journal of biological chemistry High 20427281
2010 Antiphospholipid antibodies (aPL) promote leukocyte-endothelial adhesion and thrombosis through ApoER2-dependent antagonism of eNOS. The mechanism involves β2GPI dimerization leading to attenuated eNOS Ser1179 phosphorylation via protein phosphatase 2A. ApoER2-/- mice are protected from aPL inhibition of eNOS, leukocyte adhesion, and thrombus formation in vivo. ApoER2 knockout mice, in vivo carotid conductance assay, eNOS phosphorylation immunoblot, PP2A activity assay, monocyte adhesion assay The Journal of clinical investigation High 21123944
2012 ApoER2 (LRP8) on endothelial cells serves as the receptor for cancer-secreted ApoE to suppress metastatic endothelial recruitment (MER) and angiogenesis. ApoE engagement of endothelial LRP8 (not LRP1) suppresses angiogenesis, and miRNAs that suppress ApoE promote metastasis via this pathway. In vivo selection, siRNA knockdown, locked nucleic acid miRNA inhibition, endothelial recruitment assays, xenograft metastasis models Cell Medium 23142051
2012 PCSK9 potentiates neuronal apoptosis by reducing ApoER2 protein levels. RNAi-mediated knockdown of PCSK9 increases ApoER2 levels and reduces neuronal apoptosis; knockdown of ApoER2 (but not VLDLR) reverses this protection. PCSK9 regulates neuronal apoptosis via ApoER2-associated ERK and JNK signaling independently of NMDA receptor function. RNAi knockdown, apoptosis assays (caspase-3, p-c-Jun), pharmacological signaling pathway inhibition, cerebellar granule neuron culture Cellular and molecular life sciences : CMLS Medium 22481440
2005 ApoER2 undergoes endocytosis via a clathrin-mediated pathway dependent on its cytoplasmic FxNPXY motif, which mediates binding to the adaptor protein Dab2. Dominant-negative eps15 and Dab2 decrease ApoER2 internalization. Lipid raft association of ApoER2 does not determine its endocytic pathway. Dominant-negative expression, nystatin treatment, clathrin inhibition, receptor internalization assay, co-immunoprecipitation with Dab2 Traffic (Copenhagen, Denmark) Medium 16101684
2009 ApoER2 and VLDLR have divergent receptor fates upon Reelin stimulation linked to their differential sorting to raft vs. non-raft membrane domains. VLDLR (non-raft) endocytoses and degrades Reelin via clathrin/endosome pathway without receptor degradation. ApoER2 (raft-resident) generates specific receptor fragments and is degraded via lysosomes, contributing to negative feedback loops. Chimeric receptor constructs, lipid raft fractionation, Reelin endocytosis assay, lysosomal degradation assay, immunoblotting The Journal of biological chemistry Medium 19948739
2009 Coagulation factor XI (FXI) is a ligand for platelet ApoER2. Platelet adhesion to FXI is abrogated by soluble recombinant ApoER2, RAP, or LDL-binding domain 1 or 2 of ApoER2. ApoER2-deficient murine platelets fail to adhere to FXI. Soluble FXI binds immobilized ApoER2 with an affinity of 61 nM. Platelet adhesion assay, ApoER2-deficient mice, surface plasmon resonance binding measurement, RAP inhibition, recombinant domain deletion mutants Arteriosclerosis, thrombosis, and vascular biology High 19661487
2005 β2-Glycoprotein I (β2GPI) binds platelet ApoER2 via domain V of dimeric β2GPI. Domain V deletion mutants lacking the phospholipid-insertion loop fail to bind ApoER2 or increase platelet adhesion to collagen, while domain I and II deletion mutants retain ApoER2 binding. Domain deletion mutants of β2GPI, immunoprecipitation, platelet adhesion assay in whole blood The Journal of biological chemistry Medium 16091370
2012 ApoER2 (LRP8) mediates Wnt/β-catenin signaling and controls osteoblast differentiation. LRP8 knockdown decreases β-catenin levels and suppresses Wnt-induced Axin2 transcription and osteoblast mineralization; LRP8 ectopic expression promotes Wnt-induced β-catenin accumulation and osteoblast differentiation. siRNA knockdown, ectopic overexpression, Wnt reporter assay, immunoblotting for β-catenin, osteoblast differentiation assay, KS483 osteoprogenitor cells Journal of bone and mineral research Medium 22589174
2015 Reelin binding to LRP8 triggers activation of a cohort of neuronal enhancers (LRN enhancers) via a synapse-to-nucleus pathway. This requires γ-secretase-dependent cleavage of LRP8 releasing its intracellular domain (ICD), which regulates synaptically generated signals. LRP8 ICD participates in transcriptional regulation of synaptic plasticity genes underlying memory formation. In vivo ChIP-seq enhancer mapping, γ-secretase inhibition, LRP8 ICD nuclear fractionation, mouse learning/memory behavioral assays, NMDA-receptor signaling assays Neuron High 25892301
2014 Sorting nexin 17 (SNX17) interacts with the NPxY endocytosis motif of ApoER2 via its FERM domain and stimulates ApoER2 recycling from early to recycling endosomes without affecting endocytic rate. SNX17 knockdown increases Reelin-induced ApoER2 degradation and reduces dendritic tree development and Reelin signaling in hippocampal neurons. GST pull-down, co-immunoprecipitation, ApoER2 recycling assay, siRNA knockdown, neuronal culture morphology, Dab1 phosphorylation assay PloS one Medium 24705369
2013 Clusterin binds directly to ApoER2 and VLDLR and is internalized by cells expressing either receptor. Clusterin binding triggers a Reelin-like signal, inducing Dab1 phosphorylation and PI3K/Akt and n-cofilin activation. Blocking clusterin in SVZ explants compromises cell proliferation and neuroblast chain formation. Ligand binding/internalization assay, Dab1 phosphorylation immunoblot, PI3K/Akt immunoblot, SVZ explant culture, clusterin blocking antibody The Journal of biological chemistry Medium 24381170
2014 Apoer2 lacking exon 16 (O-linked sugar domain) shows reduced extracellular cleavage and consequently impaired γ-secretase-dependent release of the ApoER2 intracellular domain. Mice expressing this variant show increased ApoER2 abundance, altered hippocampal spine density, glutamate receptor abundance, and synaptic efficacy. Knock-in mice, proteolytic cleavage assay, spine density quantification, glutamate receptor immunoblot, hippocampal LTP electrophysiology, behavioral tests Science signaling High 25429077
2013 Presenilin 1 (PS1)/γ-secretase processes ApoER2 to generate an intracellular C-terminal fragment (CTF). The ApoER2 CTF binds to the RELN promoter region and suppresses reelin transcription at the transcriptional level. PS1 conditional knockout mice show increased ApoER2 and reelin protein levels. PS1 conditional knockout mice, luciferase reporter assay, nuclear fractionation, chromatin immunoprecipitation (ChIP), pharmacological γ-secretase inhibition FASEB journal High 24344333
2017 ApoER2 ectodomain adopts an intermediate contracted-open conformation when complexed with the signaling-competent Reelin fragment at neutral pH, different from LDLR. Crystallographic analysis identifies an auxiliary low-affinity binding interface; pH shift during endocytosis weakens this auxiliary interface and destabilizes the ligand-receptor complex, priming ligand release prior to internalization. X-ray crystallography of full-length ApoER2 ectodomain-Reelin fragment complex, mutational analysis, pH-dependent binding assays EMBO reports High 28446613
2018 The apoER2 cytoplasmic tail serves as a scaffold for aPL-induced assembly and activation of heterotrimeric PP2A in endothelial cells. Dab2 recruitment to the apoER2 NPXY motif promotes activating L309 methylation of the PP2A catalytic subunit by leucine methyl transferase-1. SHC1 recruits PP2A scaffolding subunit to the proline-rich apoER2 C-terminus, mediating inhibitory dephosphorylation of Akt and eNOS. This apoER2-Dab2-SHC1 complex underlies aPL-invoked thrombosis in mice. Co-immunoprecipitation, endothelial cell PP2A activity assay, site-specific mutational analysis of apoER2 domains, mouse thrombosis model, apoER2 knockout mice Blood High 29500169
2019 ApoER2 participates in APC (anaphase-promoting complex)/CDC20 complex formation during mitosis. In apoER2-deficient smooth muscle cells, PP2A-C fails to interact with CDC20, resulting in inactive APC and impaired cytokinesis abscission, leading to cell cycle arrest at metaphase/anaphase and premature cell senescence. Co-immunoprecipitation of apoER2 with PP2A catalytic subunit and CDC20, cell cycle protein immunoblotting, β-galactosidase senescence assay, p16INK4a immunofluorescence, Lrp8 knockout mice Arteriosclerosis, thrombosis, and vascular biology Medium 31412739
2009 The signaling motifs in the Apoer2 cytoplasmic domain are functionally dissociable from Sepp1 (selenoprotein P) uptake. Knock-in mice with signaling-impaired Apoer2 cytoplasmic domain mutations have normal brain and testis selenium concentrations, demonstrating that neurological defects in these mice result from disrupted Reelin signaling, not impaired selenium uptake. Knock-in mice with cytoplasmic domain mutations, selenium concentration measurement in tissues, neurological phenotyping, sperm motility analysis Biological chemistry High 19007311
2012 Long isoform selenoprotein P (Sepp1) is taken up by L8 myoblast cells via an apoER2-mediated mechanism requiring binding to heparin sulfate proteoglycans. siRNA knockdown of apoER2 (but not Lrp1) inhibits 75Se uptake from Sepp1. Lysosomal acidification is required for Sepp1 digestion and selenium utilization but not for Sepp1 uptake itself. siRNA knockdown, 75Se radiolabeled uptake assay, affinity chromatography with mass spectrometry, protamine/chlorate treatment, lysosomal acidification inhibition The Journal of biological chemistry High 22761431
2006 FE65 interacts with ApoER2 via its N-terminal PTB domain, acting as an intracellular bridge between ApoER2 and APP. Full-length FE65 increases surface expression of ApoER2, increases secreted APP and ApoER2 forms, and decreases Aβ production. Both PTB domains of FE65 must be present simultaneously for effects on APP/ApoER2 processing. Co-immunoprecipitation, surface protein biotinylation, live cell staining, COS7 cell transfection, Aβ ELISA The Journal of biological chemistry Medium 16638748
2007 ApoER2 expression increases APP association with lipid rafts, promotes gamma-secretase activity, and increases Aβ production while decreasing APP internalization. The increased Aβ production is dependent on the integrity of the NPxY endocytosis motif of ApoER2. ApoER2 physically interacts and co-localizes with APP. Co-immunoprecipitation, APP internalization rate assay, lipid raft fractionation, gamma-secretase activity assay, Aβ ELISA, NPxY motif mutagenesis Molecular neurodegeneration Medium 17620134
2014 ApoE3 binding to ApoER2 stimulates eNOS, promotes endothelial cell migration, and attenuates monocyte-endothelial adhesion in endothelial cells. ApoE4 does not stimulate eNOS or migration and selectively antagonizes ApoE3/ApoER2 actions, requiring the N-terminal to C-terminal interaction that distinguishes ApoE4 from ApoE3. The LRP8 R952Q variant is a loss-of-function variant of ApoER2 in endothelium; ApoER2-/- mice show decreased carotid reendothelialization and exaggerated neointima formation. eNOS activity assay, endothelial cell migration assay, monocyte adhesion assay, ApoER2 knockout mouse carotid reendothelialization, neointima formation model, adenoviral apoE expression Proceedings of the National Academy of Sciences of the United States of America High 25197062
2017 The E3 ubiquitin ligase IDOL determines synaptic ApoER2 protein levels in response to neuronal activation and regulates dendritic spine morphogenesis. IDOL-dependent ApoER2 ubiquitination modulates filopodia initiation and synapse maturation. IDOL knockout in neurons causes ApoER2 overexpression, impaired activity-dependent spine remodeling, and defective LTP. IDOL knockout neurons, ApoER2 protein level immunoblot, dendritic spine imaging, hippocampal LTP electrophysiology, experience-dependent barrel cortex plasticity assay, learning/memory behavioral tests eLife High 28891791
2017 GRIP1 binds ApoER2 and bridges a complex including ApoER2, ephrinB2, and AMPA receptors at the postsynapse. Neuronal activity induces ApoER2-ephrinB2 association; phosphorylation of ephrinB2 Ser-9 is essential for complex stability. In vivo mutation of ephrinB2 Ser-9 disrupts the complex, eliminates ApoER2 downstream signaling, and impairs activity-induced AMPA receptor insertion and LTP. Co-immunoprecipitation, knock-in ephrinB2 Ser-9 mutant mice, AMPA receptor surface insertion assay, hippocampal LTP electrophysiology, compound genetics Cell reports High 28978486
2016 Antisense oligonucleotide (ASO)-mediated correction of ApoER2 exon 19 splicing in Alzheimer's disease mice improves synaptic function and learning/memory. The balance of ApoER2 exon 19 splicing is deregulated in AD patient postmortem brain tissue. Exon 19 is required for ApoER2 signaling. ASO treatment in AD transgenic mice, splice variant analysis in human postmortem brain, synaptic function electrophysiology, Morris water maze behavioral testing EMBO molecular medicine Medium 26902204
2016 Presenilin-1 (PS1) mutations alter ApoER2 processing and trafficking. PS1 mutation R278I impairs γ-secretase cleavage of ApoER2 at baseline and after Reelin treatment. PS1 L282V mutation reduces cell-surface levels of ApoER2 without affecting total levels, indicating a trafficking defect. PS1 M146V permits accumulation of ApoER2 CTFs after Reelin treatment. PS1 mutant cell lines, ApoER2 CTF immunoblot, cell-surface protein biotinylation, γ-secretase inhibitor treatment, Reelin stimulation Neurobiology of aging Medium 27810638
2015 ApoER2 and Reelin are expressed in regenerating peripheral nerves and regulate Schwann cell migration. Reelin activates Rac1 at the leading edge of Schwann cells (detected by FRET). ApoER2 exon-19-containing splice variant (with proline-rich insert) binds PAR3. Tiam1, a Rac1-specific GEF, is required for Reelin-induced Schwann cell migration, and PAR3 associates with Tiam1 and ApoER2. FRET experiments for Rac1 activation, co-immunoprecipitation of ApoER2-PAR3, siRNA knockdown of Tiam1/PAR3/ApoER2, Schwann cell migration assay, peripheral nerve injury model Molecular and cellular neurosciences Medium 26386179
2019 ApoER2 homo- and hetero-oligomers are formed in the absence of Reelin. Full-length Reelin binding rearranges ApoER2 homo-oligomers into higher-order receptor clusters, which leads to Dab1 phosphorylation. Binding of the central Reelin fragment does not increase cluster size and does not induce Dab1 phosphorylation, but can induce ApoER2 hetero-oligomerization with VLDLR without triggering the canonical signal. Time-resolved fluorescence anisotropy, fluorescence lifetime imaging microscopy (FLIM), FRET, HEK293 cells expressing tagged receptors Frontiers in molecular neuroscience Medium 30873003
2021 VLDLR and ApoER2 (LRP8) are functional entry receptors for multiple alphaviruses including Semliki forest virus, eastern equine encephalitis virus, and Sindbis virus. The alphavirus E2-E1 glycoproteins interact with the ligand-binding domains of VLDLR and ApoER2. VLDLR LBD-Fc fusion protein blocks virus infection in cell culture and protects mice from lethal challenge. Ectopic receptor expression facilitating viral entry, virus-like particle internalization assay, LBD-Fc blocking experiments, mouse lethal challenge model Nature High 34929721
2023 LRP8 is a key determinant protecting MYCN-amplified neuroblastoma cells from ferroptosis by mediating selenoprotein P (SELENOP) uptake to supply selenocysteine required for GPX4 translation. Genetic deletion of LRP8 causes ferroptosis due to insufficient selenocysteine supply; this dependency is specific to cells with low expression of alternative selenium uptake pathways (system Xc-). CRISPR activation screen, LRP8 knockout (constitutive and inducible) in orthotopic xenografts, ferroptosis assays, GPX4 immunoblot, selenium uptake assay EMBO molecular medicine High 37435859
2009 Splice variants of ApoER2 with different numbers of ligand-binding type A (LA) repeats (LA1237 vs. LA12378) differ in Reelin-binding affinity. LA8 and Reelin repeat 8 (RR8) interfere with the interaction between the central Reelin fragment and ApoER2. Proteolytic cleavage of Reelin and alternative splicing of ApoER2 contribute to fine regulation of Reelin signaling. Quantitative binding assay between Reelin isoforms/fragments and ApoER2 splice variants, monoclonal antibody specificity, primary cortical neuron signaling assays Neuroscience research Medium 19167437
2025 LRP8 is a receptor for tick-borne encephalitis virus (TBEV). LRP8 downregulation reduces TBEV infection in human cells and overexpression enhances it. LRP8 binds directly to the TBEV E glycoprotein and mediates viral attachment and internalization. An LRP8-based soluble decoy blocked TBEV infection in human cell lines and neuronal cells and protected mice from lethal challenge. Genome-scale CRISPR-Cas9 screen, LRP8 overexpression/knockdown, direct LRP8-E glycoprotein binding assay, viral attachment/internalization assay, LRP8 soluble decoy in cell culture and mouse lethal challenge Nature High 40993380
2014 NGF-induced TrkA activation in PC12 cells induces ApoER2 proteolytic processing via metalloproteinase activity, independently of MAPK and PI3K. In primary cortical neurons, BDNF (TrkB ligand) also regulates ApoER2 proteolysis. Reelin regulates proteolysis of its own receptor ApoER2 but does not affect p75NTR processing. TrkA/TrkB activation in cell lines and primary neurons, metalloproteinase inhibitors, MAPK/PI3K pharmacological inhibition, ApoER2 shedding/CTF immunoblot BMC neuroscience Medium 25233900
2022 Human APOER2 isoforms lacking different numbers of ligand-binding repeats generate differential amounts of C-terminal fragments (CTFs) in response to ApoE peptide. Isoform Δex5-8 generates the highest CTF; Δex4-6 generates the lowest. Differential CTF generation correlates with proteolytic release of the transcriptionally active ICD (mediated via Mint1 adaptor). Loss of mouse Apoer2 decreases miniature excitatory event frequency; rescue with human APOER2-FL or Δex4-6 (but not Δex5-8) restores this frequency. Identification of 25 human APOER2 isoforms by gene-specific PCR sequencing, CTF immunoblot, ICD nuclear fractionation, Mint1 interaction assay, Apoer2 knockout neurons with lentiviral rescue, miniature EPSC recordings The Journal of neuroscience Medium 35414534
2023 An ApoER2 variant with a highly glycosylated O-linked sugar domain has a high affinity for SeP (Kd = 0.67 nM) in Jurkat cells. This high-affinity variant mediates selenium transport via SeP through a selenocysteine lyase-independent pathway, in contrast to the Sec lyase-dependent degradation pathway in low-affinity cells. Acidification of intracellular vesicles is necessary for selenium transport via SeP in both cell types. ApoER2 variant characterization, SeP binding affinity measurement, siRNA knockdown, 75Se uptake assay, selenocysteine lyase inhibition, lysosomal acidification inhibition The Journal of biological chemistry Medium 37406814
2013 Dab1 mediates colocalization of multi-adaptor CIN85 with ApoER2 in neurons. Stimulation with active Reelin fragment recruits CIN85 to plasma membrane domains where it colocalizes with ApoER2 and Dab1, then moves to EEA1-labeled early endosomes. Tyrosine phosphorylation of Dab1 strengthens its binding to CIN85. Co-immunoprecipitation, immunofluorescence colocalization, Reelin stimulation, endosome marker co-localization, phospho-Dab1 binding assay Genes to cells Medium 23506116
2021 ApoER2 (apoER2) activation by PP2A in trophoblasts driven by antiphospholipid antibodies promotes preeclampsia in a mouse model of antiphospholipid syndrome, demonstrating ApoER2-PP2A signaling in trophoblasts as a mechanistic driver of preeclampsia pathogenesis. Mouse model of antiphospholipid syndrome, trophoblast-specific genetic approaches, PP2A activity assays, preeclampsia phenotypic readouts 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 395 18039658
2005 Modulation of synaptic plasticity and memory by Reelin involves differential splicing of the lipoprotein receptor Apoer2. Neuron 385 16102539
2012 Convergent multi-miRNA targeting of ApoE drives LRP1/LRP8-dependent melanoma metastasis and angiogenesis. Cell 347 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 185 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 161 21123944
2007 Divergent roles of ApoER2 and Vldlr in the migration of cortical neurons. Development (Cambridge, England) 136 17913789
2015 LRP8-Reelin-Regulated Neuronal Enhancer Signature Underlying Learning and Memory Formation. Neuron 133 25892301
2012 PCSK9 regulates neuronal apoptosis by adjusting ApoER2 levels and signaling. Cellular and molecular life sciences : CMLS 120 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 119 20427281
2021 VLDLR and ApoER2 are receptors for multiple alphaviruses. Nature 112 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 82 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 75 28292942
2011 Similarities and differences in structure, expression, and functions of VLDLR and ApoER2. Molecular neurodegeneration 75 21554715
2018 The Reelin Receptors Apolipoprotein E receptor 2 (ApoER2) and VLDL Receptor. International journal of molecular sciences 73 30304853
2002 Dentate granule cells in reeler mutants and VLDLR and ApoER2 knockout mice. Experimental neurology 72 12093079
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
2023 LRP8-mediated selenocysteine uptake is a targetable vulnerability in MYCN-amplified neuroblastoma. EMBO molecular medicine 67 37435859
2018 Antiphospholipid antibodies induce thrombosis by PP2A activation via apoER2-Dab2-SHC1 complex formation in endothelium. Blood 66 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) 63 16101684
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
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 57 22589174
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
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 49 22761431
2014 Differential splicing and glycosylation of Apoer2 alters synaptic plasticity and fear learning. Science signaling 44 25429077
2018 Targeting LRP8 inhibits breast cancer stem cells in triple-negative breast cancer. Cancer letters 42 30227220
2008 The Reelin receptors Apoer2 and Vldlr coordinate the patterning of Purkinje cell topography in the developing mouse cerebellum. PloS one 40 18301736
2007 Platelets express three different splice variants of ApoER2 that are all involved in signaling. Journal of thrombosis and haemostasis : JTH 40 17470198
2014 Sorting nexin 17 regulates ApoER2 recycling and reelin signaling. PloS one 38 24705369
2013 ApoER2 processing by presenilin-1 modulates reelin expression. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 36 24344333
2016 Interfering of the Reelin/ApoER2/PSD95 Signaling Axis Reactivates Dendritogenesis of Mature Hippocampal Neurons. Journal of cellular physiology 33 27653801
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 31 31412739
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) 31 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 30 33779882
2020 Genome-scale CRISPR activation screening identifies a role of LRP8 in Sorafenib resistance in Hepatocellular carcinoma. Biochemical and biophysical research communications 30 32312520
2023 Role of Lipid Rafts on LRP8 Signaling Triggered by Anti-β2-GPI Antibodies in Endothelial Cells. Biomedicines 29 38137358
2019 SFRS11 Loss Leads to Aging-Associated Cognitive Decline by Modulating LRP8 and ApoE. Cell reports 27 31269452
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 26 26386179
2013 ApoER2 and VLDLr are required for mediating reelin signalling pathway for normal migration and positioning of mesencephalic dopaminergic neurons. PloS one 26 23976984
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
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
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
2018 PCSK9: A potential regulator of apoE/apoER2 against inflammation in atherosclerosis? Clinica chimica acta; international journal of clinical chemistry 23 29727700
2012 Reelin together with ApoER2 regulates interneuron migration in the olfactory bulb. PloS one 23 23209795
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 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
2015 Convergent Lines of Evidence Support LRP8 as a Susceptibility Gene for Psychosis. Molecular neurobiology 20 26637325
2007 The reelin receptors VLDLR and ApoER2 regulate sensorimotor gating in mice. Neuropharmacology 20 17261317
2025 LRP8 is a receptor for tick-borne encephalitis virus. Nature 19 40993380
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 19 37406814
2017 GRIP1 Binds to ApoER2 and EphrinB2 to Induce Activity-Dependent AMPA Receptor Insertion at the Synapse. Cell reports 19 28978486
2016 Presenilin 1 mutations influence processing and trafficking of the ApoE receptor apoER2. Neurobiology of aging 19 27810638
2009 Splicing variations in the ligand-binding domain of ApoER2 results in functional differences in the binding properties to Reelin. Neuroscience research 19 19167437
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 19 19846452
2017 Structural basis for ligand capture and release by the endocytic receptor ApoER2. EMBO reports 18 28446613
2009 Differential functions of the Apoer2 intracellular domain in selenium uptake and cell signaling. Biological chemistry 18 19007311
2023 ApoER2-Dab1 disruption as the origin of pTau-associated neurodegeneration in sporadic Alzheimer's disease. Acta neuropathologica communications 17 38093390
2021 Protein Phosphatase 2A Activation Via ApoER2 in Trophoblasts Drives Preeclampsia in a Mouse Model of the Antiphospholipid Syndrome. Circulation research 17 34404233
2013 Contributions of VLDLR and LRP8 in the establishment of retinogeniculate projections. Neural development 17 23758727
2017 Clusterin signals via ApoER2/VLDLR and induces meiosis of male germ cells. American journal of translational research 16 28386352
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
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
2020 LRP8 activates STAT3 to induce PD-L1 expression in osteosarcoma. Tumori 14 33054597
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
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
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

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