Affinage

SORL1

Sortilin-related receptor · UniProt Q92673

Length
2214 aa
Mass
248.4 kDa
Annotated
2026-06-10
100 papers in source corpus 50 papers cited in narrative 50 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

SORL1/SORLA is a large multidomain type-I transmembrane sorting receptor that governs the intracellular trafficking of amyloid precursor protein (APP) and a broad set of other cargoes through the trans-Golgi network (TGN), endosomal, and cell-surface compartments, and its loss is a central driver of the endolysosomal pathology underlying Alzheimer's disease (PMID:16174740, PMID:17220890, PMID:34133918). Synthesized as a furin-cleaved proreceptor whose VPS10P domain becomes competent for ligand binding (PMID:11294867), SORLA binds APP directly through its complement-type repeat (CR) cluster to form a 1:1 complex, retains APP in the TGN, reduces its co-residence with BACE1, and thereby suppresses amyloidogenic processing to Aβ (PMID:16407538, PMID:16489755, PMID:25525276); its VPS10P domain additionally captures nascent Aβ and routes it to lysosomes for degradation (PMID:24523320). SORLA's itinerary is dictated by its cytoplasmic tail, which engages distinct adaptors—GGA1/2 via a ψ-ψ-X-X-φ motif, the retromer VPS26 subunit via a FANSHY sequence, PACS-1, AP-1/AP-2, and SNX27—such that retromer-mediated retrograde transport restrains APP processing while GGA-mediated anterograde transport directs Aβ to lysosomes (PMID:17646382, PMID:11821067, PMID:22279231, PMID:24001769, PMID:26377460, PMID:27466343). SORLA dimerizes via its 3Fn and VPS10P domains within retromer-positive endosomal tubules to promote APP recycling, and disruption of this dimerization or of receptor maturation by familial missense variants causes ER retention, reduced surface delivery, and increased Aβ (PMID:34922638, PMID:36652482, PMID:39226352, PMID:38244079). Beyond APP, SORLA functions as a general endosomal sorting hub that controls recycling and lysosomal targeting of TrkB, GLUA1, the insulin receptor, and HER2/HER3, and modulates GDNF/GFRα1, IL-6, and EphA4 signaling, while its shed ectodomain activates EGFR/ERK-dependent neurite outgrowth (PMID:23333276, PMID:23977241, PMID:27322061, PMID:31138794, PMID:35226190, PMID:32601248). Loss of SORLA—by knockout, CRISPR haploinsufficiency, or trafficking-defective variants—consistently produces early-endosome enlargement and endolysosomal and autophagic dysfunction in neurons, a phenotype that places APP, PSEN1, and SORL1 in a common endolysosomal pathway and that can be relieved by lowering APP (PMID:32492427, PMID:34133918, PMID:35226190). Truncating and missense SORL1 variants are causative for familial Alzheimer's disease through these loss-of-function mechanisms (PMID:24523320, PMID:34922638, PMID:39226352, PMID:38244079).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2001 High

    Establishing that SORLA is a functional endocytic receptor required showing it matures into a ligand-binding form; furin cleavage of the proreceptor was shown to activate the VPS10P domain for binding of neuropeptides, RAP, ApoE, and lipoprotein lipase.

    Evidence Furin cleavage and ligand-binding/endocytosis assays with surface-expression quantification

    PMID:11294867

    Open questions at the time
    • Did not connect receptor activation to a specific physiological cargo in vivo
    • Cell-surface vs. Golgi pool dynamics not mechanistically resolved
  2. 2002 Medium

    How SORLA tail is read by the sorting machinery was unknown; the cytoplasmic tail was shown to bind GGA1/GGA2 through a novel ψ-ψ-X-X-φ motif distinct from sortilin/MPR motifs, defining a basis for Golgi-endosome routing.

    Evidence Co-IP with site-directed mutagenesis of C-terminal residues

    PMID:11821067

    Open questions at the time
    • Functional consequence for cargo sorting not yet tested
    • Single-lab Co-IP without structural detail
  3. 2005 High

    The link between SORLA and APP was established by showing direct interaction and that SORLA redistributes APP to the Golgi, reducing Aβ, with brain Aβ elevated in knockout mice—establishing SORLA as an APP sorting receptor.

    Evidence Reciprocal Co-IP, colocalization, neuronal overexpression, SORLA-KO mouse

    PMID:16174740

    Open questions at the time
    • Binding interface not mapped
    • Mechanism of Aβ reduction (retention vs. degradation) unresolved
  4. 2006 High

    The molecular basis of SORLA's protective effect was refined by mapping the APP-binding site to the CR-cluster forming a 1:1 complex, and by demonstrating that SORLA reduces BACE1-APP co-residence and BACE-dependent cleavage.

    Evidence SPR and analytical ultracentrifugation of recombinant fragments; FRET and APP-shedding assays

    PMID:16407538 PMID:16489755

    Open questions at the time
    • In vivo relevance of stoichiometry not tested
    • Did not address adaptor-dependent trafficking
  5. 2006 High

    Whether SORLA itself is processed like other amyloid-pathway receptors was addressed by showing TACE shedding followed by γ-secretase cleavage releases a cytoplasmic domain that translocates to the nucleus and activates transcription.

    Evidence γ-secretase inhibitors, presenilin KO cells, NLS mutagenesis, reporter assays

    PMID:16531402

    Open questions at the time
    • Transcriptional target genes of the released domain not identified
    • Physiological role of nuclear signaling unknown
  6. 2007 High

    The trafficking logic was extended by showing SORLA retains APP in the TGN dependent on GGA and PACS-1, and that SORL1 knockdown mis-sorts APP into Aβ-generating compartments, linking expression level to amyloidogenesis and to genetic risk.

    Evidence Dominant-negative adaptors, fractionation, Aβ ELISA, siRNA, genetic association

    PMID:17220890 PMID:17855360

    Open questions at the time
    • Causality of intronic variants on expression not directly demonstrated
    • Adaptor hierarchy at distinct trafficking steps not separated
  7. 2007 High

    The adaptor repertoire controlling SORLA itinerary was defined by identifying the acidic-cluster-dileucine/GGA-binding motifs for Golgi-endosome transport and AP-2 endocytosis, with AP-1 essential for Golgi-endosome cycling and retromer (SNX1/Vps35) for endosomal retrieval.

    Evidence Chimeric receptors, AP-1 mu1-deficient cells, Co-IP, trafficking assays

    PMID:17646382

    Open questions at the time
    • Quantitative flux through each route not measured
    • Retromer recognition sequence not yet defined
  8. 2012 High

    The retromer-recognition determinant was identified as a FANSHY sequence bound by VPS26; mutating it redistributes SORLA away from the TGN and mis-sorts APP into amyloidogenic compartments without affecting APP binding, dissociating localization from cargo binding.

    Evidence FANSHY mutagenesis, VPS26 knockdown, fractionation, Aβ ELISA, Co-IP

    PMID:22279231

    Open questions at the time
    • Did not separate retrograde vs. anterograde contributions to Aβ
    • In vivo confirmation pending at this stage
  9. 2012 Medium

    Adaptor specificity for the amyloid phenotype was sharpened by showing GGA1 (not GGA2/3) selectively governs LR11 endocytic trafficking and its modulation of APP processing, with BACE1 sorting determinants also implicated.

    Evidence Selective siRNA, GGA-site and BACE1 mutagenesis, Aβ ELISA

    PMID:22621900

    Open questions at the time
    • Single-lab study
    • Endogenous-level relevance not tested
  10. 2013 High

    Anterograde vs. retrograde routes were assigned distinct functions in vivo using PACS1-, retromer-, and GGA-binding mutant mice: PACS1/retromer disruption depletes TGN SORLA and enhances APP processing, while GGA disruption raises brain Aβ via failed anterograde lysosomal Aβ targeting.

    Evidence Transgenic mice with trafficking-mutant SORLA, brain Aβ and TGN localization assays

    PMID:23813966 PMID:24001769

    Open questions at the time
    • Molecular machinery of anterograde Aβ lysosomal delivery incompletely defined
    • Contribution of SORLA-independent PACS1 effects confounds interpretation
  11. 2014 High

    A direct Aβ-clearance function was established by showing the VPS10P domain binds nascent Aβ and routes it to lysosomes; a familial AD mutation impairs this binding, and SORLA overexpression lowers brain Aβ.

    Evidence Recombinant VPS10P binding, SORLA-overexpressing mice, lysosomal targeting, mutagenesis

    PMID:24523320

    Open questions at the time
    • Relative contribution of Aβ capture vs. APP retention to net Aβ lowering unquantified
    • Structural basis of VPS10P–Aβ binding unresolved
  12. 2015 High

    The two trafficking routes were definitively separated in vivo and the CR-cluster mechanism refined: retromer disruption enhances APP processing whereas GGA disruption raises Aβ through anterograde defects, and CR-domain integrity controls APP O-glycosylation that gates amyloidogenic processing.

    Evidence Trafficking-mutant transgenic mice; CR-deletion/mutant cell lines, glycosylation analysis, Aβ/sAPP ELISA

    PMID:25525276 PMID:26377460

    Open questions at the time
    • How glycosylation alters secretase access not mechanistically detailed
    • Single-lab glycosylation findings
  13. 2016 Medium

    SORLA's role as a general recycling receptor was extended by showing SNX27 forms a ternary complex with SORLA and APP that drives APP endosome-to-surface recycling and favors non-amyloidogenic cleavage in a SORLA-dependent manner.

    Evidence Co-IP, SNX27/SORLA double knockdown, APP recycling kinetics, surface cleavage products

    PMID:27466343

    Open questions at the time
    • Single-lab Co-IP
    • Structural basis of SNX27 tail recognition not defined
  14. 2020 High

    Whether SORL1 loss causes amyloid-independent organelle pathology was tested in isogenic hiPSC neurons: SORL1 depletion enlarges early endosomes and mis-localizes APP, and BACE inhibition fails to rescue endosome enlargement, demonstrating an APP-processing-independent endosomal defect that is neuron-specific.

    Evidence CRISPR SORL1 KO hiPSCs, endosome quantification, BACE inhibitor epistasis, neuron vs. microglia comparison

    PMID:32492427

    Open questions at the time
    • Cargo whose mis-trafficking drives enlargement not identified here
    • Mechanism of neuronal specificity unexplained
  15. 2021 High

    Gene-dosage and pathway placement were established by an isogenic WT/het/null series showing haploinsufficiency enlarges endosomes while complete loss adds lysosomal and autophagy defects, all relieved by APP-lowering ASO—placing PSEN1, APP, and SORL1 in one endolysosomal pathway.

    Evidence CRISPR truncation series in hiPSC neurons, endolysosomal/autophagy assays, APP ASO rescue

    PMID:34133918

    Open questions at the time
    • Why APP lowering rescues despite APP-independent endosome phenotype reported earlier remains to be reconciled
    • Lysosomal step affected not pinpointed
  16. 2021 High

    The loss-of-function mechanism of disease variants was defined by showing rare missense variants (R332W, S577P, R654W) impair receptor maturation and cause ER retention with increased Aβ at endogenous expression levels.

    Evidence Large variant screen in HEK293, CRISPR hiPSCs, ER retention and PM delivery assays, Aβ ELISA

    PMID:34922638

    Open questions at the time
    • Structural basis of misfolding per variant not fully resolved
    • Whether all variants act solely via ER retention untested
  17. 2022 High

    The cargo spectrum and synaptic consequences of SORL1 loss were broadened by showing impaired endosomal trafficking of GLUA1, TRKB, and APP with reduced surface recycling and diminished synaptic activity, reversible by increased SORL1.

    Evidence Isogenic hiPSC neurons with depletion/overexpression, trafficking and recycling assays, MEA, RNA-seq

    PMID:35226190

    Open questions at the time
    • Direct binding of SORLA to each cargo tail not all mapped
    • Link between specific cargo and synaptic deficit not isolated
  18. 2023 High

    The structural basis of SORLA function was advanced by crystallography showing dimerization via 3Fn and VPS10P domains in retromer-positive tubules, where a 3Fn-transmembrane-cytoplasmic fragment enhances retromer-dependent APP recycling and reduces Aβ.

    Evidence X-ray crystallography, AI modeling, domain-fragment dimerization and APP recycling assays

    PMID:36652482

    Open questions at the time
    • Full-length receptor dimer architecture not resolved
    • Regulation of dimerization in cells unclear
  19. 2024 High

    Dimerization was shown to be functionally essential and disease-relevant: the familial p.Y1816C variant impairs endosomal homodimerization, reducing surface trafficking and ectodomain shedding and enlarging endosomes, with rescue by the 3Fn-minireceptor.

    Evidence Family segregation, CRISPR hiPSC neurons, dimerization/trafficking/shedding assays, minireceptor rescue

    PMID:39226352

    Open questions at the time
    • Whether dimerization defect alone accounts for full neuronal phenotype untested
    • Therapeutic feasibility of minireceptor rescue in vivo unknown
  20. 2024 Medium

    An additional disease-variant mechanism was characterized by showing the familial p.R953C YWTD-domain variant causes ER retention with decreased maturation, shedding, and endosomal trafficking, reinforcing maturation defects as a recurrent loss-of-function route.

    Evidence Family segregation, ER retention, maturation/shedding, endosomal trafficking assays

    PMID:38244079

    Open questions at the time
    • Single-lab characterization
    • Structural consequence within YWTD domain not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SORLA's diverse cargo-sorting roles (APP, TrkB, GLUA1, insulin receptor, HER2/3) are coordinated, prioritized, and regulated within a single receptor remains unresolved, as does the structural basis of full-length receptor dimerization and the precise lysosomal step disrupted by complete loss.
  • No unified model of cargo selectivity
  • Full-length structure and regulated dimerization undefined
  • Tissue-specific cargo priorities unmapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0038024 cargo receptor activity 6 GO:0060090 molecular adaptor activity 4 GO:0008289 lipid binding 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005768 endosome 5 GO:0005764 lysosome 4 GO:0005794 Golgi apparatus 4 GO:0005886 plasma membrane 4 GO:0005634 nucleus 1
Pathway
R-HSA-1643685 Disease 6 R-HSA-9609507 Protein localization 6 R-HSA-162582 Signal Transduction 5 R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-9612973 Autophagy 1
Partners
APPBACE1EPHA4GGA1HER2PACS1SNX27VPS26
Complex memberships
SORLA-APP complexSORLA-HER2-HER3 trimeric complexretromer (VPS26-associated)

Evidence

Reading pass · 50 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 SorLA/LR11 directly interacts with APP in vitro and in living cells, colocalizes with APP in endosomal and Golgi compartments, and acts as a sorting receptor that redistributes APP to the Golgi, reducing processing to Aβ. Ablation of SorLA in knockout mice increases brain Aβ levels. Co-immunoprecipitation, colocalization imaging, overexpression in neurons, SorLA-knockout mouse model Proceedings of the National Academy of Sciences of the United States of America High 16174740
2006 SorLA's cytoplasmic domain contains an acidic cluster-dileucine-like motif and a GGA-binding site that mediate Golgi-endosome transport and AP-2-dependent endocytosis. AP-1 adaptor complex is essential for SorLA transport between Golgi membranes and endosomes; SNX1 and Vps35 (retromer components) are engaged in retraction of the receptor from endosomes. Chimeric receptor constructs, AP-1 mu1-chain-deficient cells, co-immunoprecipitation, trafficking assays Molecular and cellular biology High 17646382
2007 SorLA acts as a retention factor for APP in trans-Golgi compartments/TGN, preventing release into processing pathways. Proper localization depends on functional interaction with adaptors GGA and PACS-1; aberrant targeting to the recycling compartment or plasma membrane causes faulty APP trafficking and increased amyloidogenic processing. Overexpression, dominant-negative adaptor proteins, subcellular fractionation, Aβ ELISA The Journal of biological chemistry High 17855360
2006 SorLA interacts with both APP (via cytoplasmic C99 domain) and BACE1 by co-immunoprecipitation, and reduces BACE-APP interactions in the Golgi as measured by FRET. Both full-length SorLA and a sorLA tail construct inhibited BACE-dependent APP cleavage, reducing secreted Aβ. Co-immunoprecipitation, FRET assay, APP-shedding assay, BACE overexpression The Journal of neuroscience : the official journal of the Society for Neuroscience High 16407538
2006 The binding site between SorLA and APP was mapped to the cluster of complement-type repeats (CR-cluster) in SorLA and the carbohydrate-linked domain of APP, forming a 1:1 stoichiometric complex, as determined by surface plasmon resonance and analytical ultracentrifugation of recombinant fragments. FRET assay, surface plasmon resonance, analytical ultracentrifugation of recombinant fragments Biochemistry High 16489755
2007 SORL1 directs trafficking of APP into recycling endosomal pathways; when SORL1 is underexpressed, APP is sorted into Aβ-generating compartments. Inherited SORL1 variants occur in intronic clusters that may regulate tissue-specific SORL1 expression. siRNA knockdown of SORL1, APP trafficking assay, genetic association study Nature genetics High 17220890
2001 SorLA is synthesized as a proreceptor cleaved by furin in late Golgi compartments, activating the Vps10p domain for ligand binding. Following activation, SorLA binds neuropeptides, receptor-associated protein, ApoE, and lipoprotein lipase, and mediates endocytosis; ~10% of full-length SorLA is expressed at the cell surface while the major pool resides in late Golgi. Furin cleavage assay, ligand binding assays, cell surface expression quantification, endocytosis assays The Journal of biological chemistry High 11294867
2002 The SorLA cytoplasmic tail binds adaptor proteins GGA1 and GGA2 via three critical C-terminal residues conforming to a novel motif (ψ-ψ-X-X-φ), distinct from the acidic cluster-dileucine motifs used by sortilin and mannose-6-phosphate receptors. Co-immunoprecipitation, mutagenesis of cytoplasmic tail residues FEBS letters Medium 11821067
2012 SorLA contains a FANSHY sequence in its cytoplasmic domain recognized by the VPS26 subunit of the retromer complex. Mutations in the VPS26 binding site redistribute SorLA to endosomes (away from TGN) without affecting APP binding, but cause APP mis-sorting into a non-Golgi compartment with increased amyloidogenic processing. Mutagenesis of FANSHY motif, VPS26 knockdown, subcellular fractionation, Aβ ELISA, co-immunoprecipitation The Journal of neuroscience : the official journal of the Society for Neuroscience High 22279231
2014 The VPS10P domain of SORLA binds nascent Aβ peptides and directs them to lysosomes for degradation. A familial AD mutation in SORL1 impairs this Aβ binding. SORLA overexpression in mice decreases brain Aβ levels via lysosomal targeting. Binding assay with recombinant VPS10P domain, SORLA-overexpressing mouse model, lysosomal targeting assay, site-directed mutagenesis Science translational medicine High 24523320
2010 ROCK2 (Rho-associated coiled-coil containing protein kinase 2) binds LR11/SorLA and phosphorylates it at serine 2206 in the cytoplasmic tail. ROCK2 inhibition reduces LR11 phosphorylation and ectodomain shedding while increasing intracellular LR11 levels. Phosphorylation at S2206 is required for LR11-mediated reduction of Aβ. 32P-labeling, LC-MS/MS identification of ROCK2 as binding partner, co-immunoprecipitation from human brain, ROCK inhibitor treatment, siRNA knockdown of ROCK2, S2206A mutagenesis, in vitro kinase assay The Journal of biological chemistry High 21147781
2013 SorLA acts as a sorting receptor for the GDNF/GFRα1 complex, directing it from the cell surface to endosomes and then to lysosomes for GDNF degradation while GFRα1 recycles, creating a GDNF clearance pathway. SorLA also targets RET for endocytosis but not degradation. SorLA-deficient mice display elevated GDNF levels, altered dopaminergic function, hyperactivity, and reduced anxiety. SorLA-deficient mouse model, co-immunoprecipitation, endocytosis/degradation assays, behavioral phenotyping Cell reports High 23333276
2011 SorLA regulates intracellular trafficking of lipoprotein lipase (LPL) by binding LPL under neutral and acidic conditions. SorLA expression redistributes LPL to endosomes and routes it to lysosomes for degradation, resulting in ~80% reduction of LPL activity in expressing cells. Co-immunoprecipitation, subcellular fractionation, LPL activity assay, immunofluorescence colocalization in primary neurons Journal of cell science Medium 21385844
2010 SORLA is expressed in epithelial cells of the thick ascending limb (TAL) of Henle's loop and functionally interacts with SPAK (Ste-20-related proline-alanine-rich kinase). SORLA deficiency causes missorting of SPAK, inability to phosphorylate NKCC2 cotransporter, and inability to reabsorb sodium and chloride during osmotic stress. SORLA-deficient mouse model, immunolocalization, co-immunoprecipitation of SORLA and SPAK, NKCC2 phosphorylation assays, renal ion transport measurements Molecular and cellular biology High 20385770
2013 SORLA is a sorting factor for the BDNF receptor TrkB, facilitating trafficking of TrkB between synaptic plasma membranes, post-synaptic densities, and cell soma. Loss of SORLA impairs neuritic transport of TrkB and blunts BDNF response in primary neurons; SORLA deficiency aggravates neuromotoric deficits in a Huntington's disease mouse model. SORLA KO neurons, live-cell imaging of TrkB trafficking, BDNF signaling assays, Huntington's disease mouse model cross PloS one Medium 23977241
2016 SORLA acts as a sorting factor for the insulin receptor (IR) in adipocytes, redirecting internalized IR from endosomes to the plasma membrane, thereby enhancing IR surface expression and strengthening insulin signal reception. Gene-dosage effects link SORLA expression to obesity and glucose tolerance in mouse models and human subjects. Mouse models with genetic loss or adipose-specific overexpression of SORLA, insulin receptor trafficking assay, co-immunoprecipitation, lipolysis assays The Journal of clinical investigation High 27322061
2015 Soluble LR11/SorLA (sLR11) suppresses thermogenesis in adipose tissue in a cell-autonomous manner via the BMP/TGFβ signaling pathway, reducing Smad phosphorylation. LR11-deficient mice are protected from diet-induced obesity with increased browning of white adipose tissue. LR11-KO mouse model, treatment of adipocytes with sLR11, Smad phosphorylation assay, metabolic phenotyping Nature communications High 26584636
2006 After TACE-mediated ectodomain shedding of SorLA, the remaining C-terminal membrane fragment is processed by γ-secretase, releasing the SorLA cytoplasmic domain and a SorLA β-peptide. The released cytoplasmic domain translocates to the nucleus (dependent on an intact NLS) and acts as a transcriptional activator in reporter gene assays. γ-secretase inhibitors, dominant-negative presenilin mutants, presenilin knockout cells, in vitro γ-secretase assay, EGFP fusion reporter, nuclear translocation imaging, reporter gene assay The Journal of biological chemistry High 16531402
2000 SorLA binds the neuropeptide head activator (HA) at the cell surface; HA stimulates metalloprotease-mediated ectodomain shedding of SorLA, translocation of SorLA from internal membranes to the cell surface, and enhanced SorLA synthesis. Blockade of SorLA shedding or antisense oligonucleotides against SorLA decreases HA-induced cell proliferation. HA-Sepharose pulldown, metalloprotease inhibitor treatment, SorLA antisense oligonucleotides, cell proliferation assay, immunostaining of SorLA subcellular localization Journal of cell science Medium 11082041
2001 LR11 overexpressed in hamster cells binds ApoE-rich lipoproteins (β-VLDL) with high affinity (similar to LDLR and VLDLR), internalizes and degrades bound β-VLDL, and promotes accumulation of cholesteryl esters and lipid droplets. RAP and β-VLDL compete for binding. Binding and internalization assays in LR11-transfected cells, cholesteryl ester assay, lipid droplet staining, competition assays with RAP Arteriosclerosis, thrombosis, and vascular biology Medium 11557679
2004 LR11 forms complexes with urokinase-type plasminogen activator receptor (uPAR) on the cell surface and inhibits LRP-mediated internalization of uPAR, resulting in increased uPAR surface localization. Both cell-anchored and secreted soluble LR11 bind uPAR. In smooth muscle cells, LR11 mediates enhanced migration through upregulation of surface uPAR levels. Neutralization of LR11 reduces cuff-induced intimal thickness in mice. Co-immunoprecipitation, uPAR internalization assay, migration assay, anti-LR11 antibody neutralization in vivo Circulation research Medium 14764453
2004 SorLA/LR11 binds components of the plasminogen-activating system (uPA, PAI-1, uPAR) and PDGF-BB similarly to LRP1, but mediates much slower internalization of bound ligand than LRP1. SorLA is substantially less efficient as a clearance receptor than LRP1, and can divert ligands from LRP1-mediated clearance. Binding assays in LRP1-deficient cells transfected with sorLA, ligand internalization rate measurements, competition assays The Biochemical journal Medium 15053742
2012 GGA1 specifically regulates LR11 endocytic trafficking; mutagenesis of the GGA-binding (DXXLL-like) motif in LR11 alters its endosomal distribution and its effects on APP trafficking and Aβ production. siRNA knockdown of GGA1 (but not GGA2 or GGA3) is necessary for both LR11 and BACE1 modulation of APP processing. BACE1-S498A mutation enhances BACE1 targeting to LR11-positive compartments and nullifies LR11-mediated Aβ reduction. siRNA knockdown of individual GGAs, GGA-binding site mutagenesis, Aβ ELISA, APP trafficking assay, BACE1 mutagenesis Molecular biology of the cell Medium 22621900
2013 Disruption of SORLA-PACS1 interaction (via transgenic mice expressing PACS1-binding-defective SORLA mutant) prevents SORLA/APP complexes from sorting to the TGN in neurons, increasing APP processing in the brain. Loss of PACS1 also impairs expression of cation-independent mannose-6-phosphate receptor and cathepsin B, providing a SORLA-independent mechanism for Aβ catabolism control. Transgenic mice expressing PACS1-binding mutant of SORLA, neuronal cell line knockdown, cathepsin B assay, APP processing assay Molecular and cellular biology High 24001769
2015 The SorLA CR-cluster (complement-type repeat domains) is essential for interaction with APP; deletion abolishes protection against APP processing. Mutation of fingerprint residues in CR-domains alters O-linked glycosylation of APP in the Golgi. These results identify CR-domain-mediated control of APP glycosylation as a mechanism by which SorLA protects APP from amyloidogenic processing. Stable SorLA CR-deletion and CR-mutant cell lines, co-immunoprecipitation, Aβ/sAPP ELISA, glycosylation analysis The Journal of biological chemistry Medium 25525276
2015 Distinct anterograde (GGA-mediated) and retrograde (retromer-mediated) SORLA trafficking routes serve discrete functions: retromer-binding disruption causes SORLA accumulation in endosomes and enhanced APP processing, while GGA-binding disruption does not affect APP processing but causes increased brain Aβ levels attributed to a defect in anterograde lysosomal targeting of Aβ. Transgenic mice expressing GGA-binding or retromer-binding mutant SORLA, brain Aβ measurement, APP processing assays, subcellular fractionation The Journal of neuroscience : the official journal of the Society for Neuroscience High 26377460
2016 SNX27 binds to the SORLA cytosolic tail to form a ternary complex with APP. SNX27 enhances cell surface SORLA and APP levels, and depletion of SNX27 or SORLA reduces APP endosome-to-cell surface recycling kinetics. SNX27 overexpression enhances non-amyloidogenic APP cleavage products in a SORLA-dependent manner. Co-immunoprecipitation, siRNA knockdown of SNX27/SORLA, APP recycling kinetics assay, surface APP cleavage product measurement The Journal of neuroscience : the official journal of the Society for Neuroscience Medium 27466343
2017 SORLA interacts with the EphA4 receptor tyrosine kinase and attenuates ephrinA1-induced EphA4 clustering and activation, limiting downstream EphA4 signaling in neurons. SORLA transgenic mice show decreased EphA4 activation and redistribution to postsynaptic densities with milder Aβ oligomer-induced deficits in LTP and memory. Active EphA4 levels in human AD brains are inversely correlated with SORLA/EphA4 association. Co-immunoprecipitation, EphA4 activation assay, SORLA transgenic mouse model, LTP and memory behavioral tests, human AD brain analysis The Journal of experimental medicine Medium 29114064
2019 SORLA co-precipitates with HER2 in cancer cells and promotes recycling of endosomal HER2 back to the plasma membrane via Rab4-dependent pathway. Depletion of SORLA triggers HER2 targeting to late endosomal/lysosomal compartments, impairs HER2-driven signaling, reduces in vivo tumor growth, and sensitizes cells to lysosome-targeting drugs. Co-immunoprecipitation, subcellular fractionation, SORLA siRNA depletion, Rab4-dependent trafficking assay, in vivo tumor growth assay Nature communications High 31138794
2020 SORL1 depletion in hiPSC-derived neurons (but not microglia) causes early endosome enlargement and altered localization of APP in early endosomes. BACE inhibition does not rescue endosome enlargement, demonstrating that this phenotype is independent of amyloidogenic APP processing. CRISPR-Cas9 SORL1 depletion in hiPSCs, endosome size quantification by confocal microscopy, BACE inhibitor treatment, cell-type-specific comparison (neurons vs. microglia) Cell reports High 32492427
2021 SORL1 truncating mutation causes haploinsufficiency and enlarged endosomes in human neurons. Complete loss of SORL1 causes additional defects in lysosome function and autophagy. Neuronal endolysosomal dysfunction from SORL1 loss is relieved by antisense oligonucleotide-mediated reduction of APP, placing PSEN1, APP, and SORL1 in a common pathway regulating the endolysosomal system. CRISPR-Cas9 truncating mutation in hiPSCs, isogenic WT/heterozygous/homozygous null neurons, endosome/lysosome functional assays, autophagy assay, APP-targeting antisense oligonucleotides Cell reports High 34133918
2022 Loss of SORL1 impairs endosomal trafficking of GLUA1, TRKB, and APP in hiPSC-derived neurons, increasing lysosomal targeting and reducing recycling endosome-to-cell surface delivery. SORL1 depletion reduces synaptic activity (measured by MEA). Increased SORL1 expression enhances endosomal recycling of APP and GLUA1. Isogenic hiPSC-derived neurons with SORL1 depletion or overexpression, confocal microscopy of endosomal trafficking, cell surface recycling and lysosomal degradation assays, MEA, RNA sequencing Cellular and molecular life sciences : CMLS High 35226190
2021 Rare SORL1 missense variants (R332W, S577P, R654W) cause impaired maturation and trafficking of the SorLA protein, with retention in the endoplasmic reticulum and reduced delivery to the plasma membrane and endosomal system. Expression of R332W and R654W in hiPSCs is associated with increased Aβ secretion, demonstrating a loss-of-function effect. Overexpression of 70 SorLA variants in HEK293 cells, CRISPR/Cas9-modified hiPSCs expressing endogenous variants, ER retention assay, plasma membrane delivery assay, Aβ ELISA, structural analysis Acta neuropathologica communications High 34922638
2014 Activation of the α2A adrenergic receptor (α2AAR) signaling disrupts APP interaction with SorLA in cells and in mouse brain, reduces Golgi localization of APP, promotes APP distribution in endosomes, and increases β-secretase cleavage and Aβ generation. α2AAR genetic deficiency and pharmacological activation, APP-SorLA co-immunoprecipitation in cells and mouse brain, subcellular APP localization by immunofluorescence, Aβ ELISA Proceedings of the National Academy of Sciences of the United States of America Medium 25404298
2013 SORLA disruption of retromer binding results in SORLA accumulation in endosomes and depletion from TGN, with overall enhanced APP processing. Disruption of GGA interaction does not affect APP processing but increases brain Aβ, attributed to defect in anterograde lysosomal Aβ targeting. Mouse models expressing SORLA variants lacking retromer or GGA binding sites, brain Aβ measurement, TGN localization assay Journal of cell science Medium 23813966
2014 LR11/SorLA mediates cellular uptake of Aβ in an ApoE-isoform-dependent manner. Co-immunoprecipitation reveals apoE4 forms a stronger complex with LR11 than apoE3 or apoE2 (apoE4>apoE3>apoE2). ApoE4 most prominently accentuates LR11-mediated cellular uptake of extracellular Aβ in a coculture assay. Co-immunoprecipitation, cellular uptake assay with FAM-labeled Aβ in coculture, LR11 overexpression Biochemical and biophysical research communications Medium 25482438
2013 SorLA acts as an APP-sorting receptor distinct from sortilin: SorLA mainly colocalizes with APP in the soma and inhibits generation of all soluble APP products, whereas sortilin interacts with APP in neurites and promotes α-secretase cleavage. Both SorLA and sortilin bind soluble APP (sAPP) via the 6A domain and mediate its internalization to different compartments. Co-immunoprecipitation, subcellular colocalization imaging, sAPP binding/internalization assay, α-secretase cleavage assay The Journal of neuroscience : the official journal of the Society for Neuroscience Medium 23283322
2015 APP mutations in the YENPTY domain (Y682G) disrupt APP complex formation with SorLA, causing endo-lysosomal dysfunction and neuronal degeneration, and alter SorLA trafficking resulting in increased SorLA secretion. APP Y682G knock-in mouse model, co-immunoprecipitation of APP/SorLA, subcellular localization of SorLA, lysosomal function assay Frontiers in cellular neuroscience Medium 25904844
2020 Soluble SORLA (sSORLA) coprecipitates with EGF receptor (EGFR) in vitro, increases EGFR Y1173 phosphorylation, and activates ERK signaling and Fos transcription in neurons. sSORLA promotes neurite outgrowth and regeneration; pharmacological EGFR or ERK inhibition reverses these effects. Co-precipitation of sSORLA and EGFR, EGFR phosphorylation assay, ERK activation assay, pharmacological inhibitors, neurite outgrowth assay, RNAseq in SORLA transgenic mouse hippocampus The Journal of neuroscience : the official journal of the Society for Neuroscience Medium 32601248
2017 SorLA mediates cellular uptake of IL-6 and circulating IL-6R in astrocytes, interacts with membrane-bound IL-6R at the cell surface to downregulate IL-6 cis-signaling, and the shed SorLA ectodomain stabilizes IL-6 and facilitates its trans-signaling. Co-immunoprecipitation of SorLA and IL-6R, IL-6 and IL-6R uptake assay, IL-6 signaling assay, ectodomain shedding assay Molecular and cellular biology Medium 28265003
2016 CLF-1 has independent binding sites for CLC, CNTFRα, and SorLA. SorLA promotes downregulation of CNTFRα pool in stimulated cells via its endocytic receptor activity, and may bind and concentrate the tripartite soluble CLC:CLF-1:CNTFRα complex on cell membranes to facilitate gp130/LIFRβ signaling. Binding assays, co-immunoprecipitation, CNTFRα turnover assay, signaling assays with CLF-1 mutants Molecular and cellular biology Medium 26858303
2014 Tetraspanin CD9 modulates ADAM17-mediated shedding of LR11 on leukocyte surfaces. CD9 overexpression reduces sLR11 release; anti-CD9 antibody treatment or CD9 shRNA knockdown increases sLR11 shedding, which is blocked by a metalloprotease inhibitor. CD9 overexpression and shRNA knockdown, anti-CD9 neutralizing antibodies, metalloprotease inhibitor treatment, sLR11 ELISA, confocal colocalization Experimental & molecular medicine Medium 24699135
2006 N-linked oligosaccharides in the VPS10p domain of SorLA/LR11 are modified with terminal β1,4-linked GalNAc-4-SO4 in kidney and brain. Two sequences with basic amino acids within the Vps10p domain mediate recognition by GalNAcTIII and GalNAcTIV transferases. Biochemical isolation of oligosaccharides, co-expression of Vps10p domain with GalNAcTIII/IV, domain mutagenesis The Journal of biological chemistry Medium 17121844
2023 SORL1 loss in iPSC-derived neurons causes neuron-specific reduction in APOE and CLU protein levels and altered lipid profiles. Enhancement of retromer-mediated trafficking rescues tau phenotypes but not APOE levels. TGF-β/SMAD signaling is implicated in SORL1 function regulating APOE RNA levels in a SORL1-dependent manner. SORL1-null iPSC-derived neurons, astrocytes, microglia, endothelial cells; retromer enhancer treatment; SMAD pathway modulation; APOE/CLU protein quantification; RNA-seq Cell reports Medium 37611586
2023 SORLA dimerizes via its fibronectin-type-III (3Fn) and VPS10p domains within retromer-positive endosomal tubules. A SORLA fragment comprising 3Fn, transmembrane, and cytoplasmic domains forms dimers and enhances retromer-dependent APP recycling and decreases amyloidogenic processing. X-ray crystallography, AI-based structural modeling, SORLA domain fragment expression and dimerization assays, APP recycling assay, Aβ measurement Proceedings of the National Academy of Sciences of the United States of America High 36652482
2024 The SORL1 p.Y1816C variant impairs SORLA homodimerization in the endosome, leading to decreased trafficking to the cell surface and reduced sSORLA shedding. iPSC-derived neurons with engineered p.Y1816C have enlarged endosomes. The trafficking defect can be rescued by expression of the SORLA 3Fn-minireceptor. Segregation analysis in three families, CRISPR-engineered iPSC-derived neurons, dimerization assay, cell surface trafficking assay, sSORLA shedding measurement, endosome size quantification, 3Fn-minireceptor rescue Proceedings of the National Academy of Sciences of the United States of America High 39226352
2021 SorLA forms a trimeric complex with HER2 and HER3, attenuating lysosomal degradation of the HER2-HER3 dimer in a Rab4-dependent manner. Heregulin-mediated signaling supports SorLA transcription downstream of the MAPK pathway. SorLA loss compromises heregulin-induced proliferation and sensitizes anti-HER2 therapy-resistant breast cancer cells to neratinib. Co-immunoprecipitation of SorLA/HER2/HER3, SorLA siRNA depletion, Rab4 trafficking assay, heregulin signaling assay, cancer spheroid and zebrafish xenograft models Oncogene Medium 33420373
2022 SORL1 haploinsufficiency in Göttingen minipigs (via CRISPR-Cas9) phenocopies the preclinical in vivo AD profile seen with APP, PSEN1, and PSEN2 mutations, resulting in elevated Aβ and tau levels preceding amyloid plaque formation. CRISPR-Cas9 gene editing in minipigs, CSF and plasma biomarker measurements (Aβ, tau) Cell reports. Medicine Medium 36099918
2024 The familial AD SORL1 p.R953C variant, occurring in the YWTD-domain, causes retention of SORL1 in the endoplasmic reticulum, decreased receptor maturation and shedding, and impaired endosomal trafficking. Family segregation analysis, SORL1 variant functional characterization in cell lines, ER retention assay, maturation/shedding assay, endosomal trafficking assay Acta neuropathologica Medium 38244079
2013 The soluble form of LR11 (sLR11) regulates hypoxia-induced, uPAR-mediated adhesion of hematopoietic stem and progenitor cells (HSPCs) to stromal cells. Hypoxia induces HIF-1α binding to the LR11 promoter, increasing LR11 expression and sLR11 production. sLR11 co-immunoprecipitates with uPAR and enhances HSPC attachment; attachment is reduced by anti-uPAR antibodies. LR11-KO mouse HSPC adhesion assay, sLR11 treatment, anti-uPAR blocking, HIF-1α knockdown, HIF-1α ChIP at LR11 promoter, co-immunoprecipitation of LR11/uPAR The Journal of biological chemistry Medium 23486467

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease. Nature genetics 929 17220890
2005 Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein. Proceedings of the National Academy of Sciences of the United States of America 547 16174740
2004 Loss of apolipoprotein E receptor LR11 in Alzheimer disease. Archives of neurology 280 15313836
2006 The lipoprotein receptor LR11 regulates amyloid beta production and amyloid precursor protein traffic in endosomal compartments. The Journal of neuroscience : the official journal of the Society for Neuroscience 246 16452683
2012 Retromer binds the FANSHY sorting motif in SorLA to regulate amyloid precursor protein sorting and processing. The Journal of neuroscience : the official journal of the Society for Neuroscience 225 22279231
2007 Sorting by the cytoplasmic domain of the amyloid precursor protein binding receptor SorLA. Molecular and cellular biology 165 17646382
2007 SorLA/LR11 regulates processing of amyloid precursor protein via interaction with adaptors GGA and PACS-1. The Journal of biological chemistry 154 17855360
2006 Interaction of the cytosolic domains of sorLA/LR11 with the amyloid precursor protein (APP) and beta-secretase beta-site APP-cleaving enzyme. The Journal of neuroscience : the official journal of the Society for Neuroscience 154 16407538
2001 Activation and functional characterization of the mosaic receptor SorLA/LR11. The Journal of biological chemistry 151 11294867
2015 Coding mutations in SORL1 and Alzheimer disease. Annals of neurology 146 25382023
2006 Molecular dissection of the interaction between amyloid precursor protein and its neuronal trafficking receptor SorLA/LR11. Biochemistry 141 16489755
2014 Lysosomal sorting of amyloid-β by the SORLA receptor is impaired by a familial Alzheimer's disease mutation. Science translational medicine 135 24523320
2017 Contribution to Alzheimer's disease risk of rare variants in TREM2, SORL1, and ABCA7 in 1779 cases and 1273 controls. Neurobiology of aging 132 28789839
2011 Meta-analysis of the association between variants in SORL1 and Alzheimer disease. Archives of neurology 132 21220680
2006 LR11/SorLA expression is reduced in sporadic Alzheimer disease but not in familial Alzheimer disease. Journal of neuropathology and experimental neurology 130 16957580
2020 Depletion of the AD Risk Gene SORL1 Selectively Impairs Neuronal Endosomal Traffic Independent of Amyloidogenic APP Processing. Cell reports 129 32492427
2008 Loss of LR11/SORLA enhances early pathology in a mouse model of amyloidosis: evidence for a proximal role in Alzheimer's disease. The Journal of neuroscience : the official journal of the Society for Neuroscience 110 19036982
2017 Characterization of pathogenic SORL1 genetic variants for association with Alzheimer's disease: a clinical interpretation strategy. European journal of human genetics : EJHG 109 28537274
2022 The Alzheimer's gene SORL1 is a regulator of endosomal traffic and recycling in human neurons. Cellular and molecular life sciences : CMLS 103 35226190
2013 Sorting receptor SORLA--a trafficking path to avoid Alzheimer disease. Journal of cell science 98 23813966
2015 SORL1 rare variants: a major risk factor for familial early-onset Alzheimer's disease. Molecular psychiatry 97 26303663
2002 The sorLA cytoplasmic domain interacts with GGA1 and -2 and defines minimum requirements for GGA binding. FEBS letters 97 11821067
2019 SORL1 genetic variants and Alzheimer disease risk: a literature review and meta-analysis of sequencing data. Acta neuropathologica 94 30911827
2014 The Role of SORL1 in Alzheimer's Disease. Molecular neurobiology 93 24833601
2013 Sortilin and SorLA display distinct roles in processing and trafficking of amyloid precursor protein. The Journal of neuroscience : the official journal of the Society for Neuroscience 93 23283322
2007 Neuronal LR11/sorLA expression is reduced in mild cognitive impairment. Annals of neurology 85 17721864
2001 LR11, a mosaic LDL receptor family member, mediates the uptake of ApoE-rich lipoproteins in vitro. Arteriosclerosis, thrombosis, and vascular biology 81 11557679
2007 Omega-3 fatty acid docosahexaenoic acid increases SorLA/LR11, a sorting protein with reduced expression in sporadic Alzheimer's disease (AD): relevance to AD prevention. The Journal of neuroscience : the official journal of the Society for Neuroscience 80 18160637
2009 Reduction of SorLA/LR11, a sorting protein limiting beta-amyloid production, in Alzheimer disease cerebrospinal fluid. Archives of neurology 76 19364929
2021 SORL1 deficiency in human excitatory neurons causes APP-dependent defects in the endolysosome-autophagy network. Cell reports 75 34133918
2014 α(2A) adrenergic receptor promotes amyloidogenesis through disrupting APP-SorLA interaction. Proceedings of the National Academy of Sciences of the United States of America 69 25404298
1999 Neuronal localization of a novel mosaic apolipoprotein E receptor, LR11, in rat and human brain. Brain research 67 10375696
1982 Transformation-dependent alterations is glycoproteins of extracellular matrix of human fibroblasts. Characterization of GP250 and the collagen-like GP140. The Journal of biological chemistry 66 6292208
2006 SorLA signaling by regulated intramembrane proteolysis. The Journal of biological chemistry 64 16531402
2000 Ectodomain shedding, translocation and synthesis of SorLA are stimulated by its ligand head activator. Journal of cell science 64 11082041
2004 LR11, an LDL receptor gene family member, is a novel regulator of smooth muscle cell migration. Circulation research 63 14764453
2016 Risk factor SORL1: from genetic association to functional validation in Alzheimer's disease. Acta neuropathologica 61 27638701
2019 SORLA regulates endosomal trafficking and oncogenic fitness of HER2. Nature communications 60 31138794
2017 Trafficking in Alzheimer's Disease: Modulation of APP Transport and Processing by the Transmembrane Proteins LRP1, SorLA, SorCS1c, Sortilin, and Calsyntenin. Molecular neurobiology 60 29079999
2016 SORL1 mutations in early- and late-onset Alzheimer disease. Neurology. Genetics 59 27822510
1999 Expression of LR11, a mosaic LDL receptor family member, is markedly increased in atherosclerotic lesions. Arteriosclerosis, thrombosis, and vascular biology 59 10559012
2013 SorLA controls neurotrophic activity by sorting of GDNF and its receptors GFRα1 and RET. Cell reports 57 23333276
2011 SorLA regulates the activity of lipoprotein lipase by intracellular trafficking. Journal of cell science 56 21385844
2016 SNX27 and SORLA Interact to Reduce Amyloidogenic Subcellular Distribution and Processing of Amyloid Precursor Protein. The Journal of neuroscience : the official journal of the Society for Neuroscience 55 27466343
2015 Soluble LR11/SorLA represses thermogenesis in adipose tissue and correlates with BMI in humans. Nature communications 55 26584636
2002 Enhanced expression of the LDL receptor family member LR11 increases migration of smooth muscle cells in vitro. Circulation 55 11956127
2011 Association of the Alzheimer's gene SORL1 with hippocampal volume in young, healthy adults. The American journal of psychiatry 54 21730226
2012 GGA1-mediated endocytic traffic of LR11/SorLA alters APP intracellular distribution and amyloid-β production. Molecular biology of the cell 53 22621900
2019 Regulatory Roles of Sortilin and SorLA in Immune-Related Processes. Frontiers in pharmacology 50 30666202
2012 SORL1 and SIRT1 mRNA expression and promoter methylation levels in aging and Alzheimer's Disease. Neurochemistry international 50 22836009
2009 Expression of SORL1 and a novel SORL1 splice variant in normal and Alzheimers disease brain. Molecular neurodegeneration 49 19889229
2016 SORLA facilitates insulin receptor signaling in adipocytes and exacerbates obesity. The Journal of clinical investigation 48 27322061
2016 Sorting receptor SORLA: cellular mechanisms and implications for disease. Cellular and molecular life sciences : CMLS 47 27832290
2010 Rho kinase II phosphorylation of the lipoprotein receptor LR11/SORLA alters amyloid-beta production. The Journal of biological chemistry 47 21147781
2004 The mosaic receptor sorLA/LR11 binds components of the plasminogen-activating system and platelet-derived growth factor-BB similarly to LRP1 (low-density lipoprotein receptor-related protein), but mediates slow internalization of bound ligand. The Biochemical journal 47 15053742
2010 SORLA/SORL1 functionally interacts with SPAK to control renal activation of Na(+)-K(+)-Cl(-) cotransporter 2. Molecular and cellular biology 46 20385770
2023 Cell-type-specific regulation of APOE and CLU levels in human neurons by the Alzheimer's disease risk gene SORL1. Cell reports 45 37611586
2008 The neuronal sortilin-related receptor gene SORL1 and late-onset Alzheimer's disease. Current neurology and neuroscience reports 44 18713574
2009 Implication of sex and SORL1 variants in italian patients with Alzheimer disease. Archives of neurology 43 19822782
2017 Identification and description of three families with familial Alzheimer disease that segregate variants in the SORL1 gene. Acta neuropathologica communications 42 28595629
2007 Association between genetic variants in sortilin-related receptor 1 (SORL1) and Alzheimer's disease in adults with Down syndrome. Neuroscience letters 40 17826910
2022 A genetically modified minipig model for Alzheimer's disease with SORL1 haploinsufficiency. Cell reports. Medicine 39 36099918
2014 ApoE-isoform-dependent cellular uptake of amyloid-β is mediated by lipoprotein receptor LR11/SorLA. Biochemical and biophysical research communications 39 25482438
2021 Brothers in arms: proBDNF/BDNF and sAPPα/Aβ-signaling and their common interplay with ADAM10, TrkB, p75NTR, sortilin, and sorLA in the progression of Alzheimer's disease. Biological chemistry 38 34619027
2015 Distinct Functions for Anterograde and Retrograde Sorting of SORLA in Amyloidogenic Processes in the Brain. The Journal of neuroscience : the official journal of the Society for Neuroscience 38 26377460
2017 SORLA attenuates EphA4 signaling and amyloid β-induced neurodegeneration. The Journal of experimental medicine 37 29114064
2014 SorLA complement-type repeat domains protect the amyloid precursor protein against processing. The Journal of biological chemistry 37 25525276
2011 Impact of SORL1 single nucleotide polymorphisms on Alzheimer's disease cerebrospinal fluid markers. Dementia and geriatric cognitive disorders 36 21997402
2015 Meta-analysis of the Association between Alzheimer Disease and Variants in GAB2, PICALM, and SORL1. Molecular neurobiology 35 26611835
2009 A study of the SORL1 gene in Alzheimer's disease and cognitive function. Journal of Alzheimer's disease : JAD 34 19584446
2022 Upregulated of ANXA3, SORL1, and Neutrophils May Be Key Factors in the Progressionof Ankylosing Spondylitis. Frontiers in immunology 33 35464477
2017 Dimerization leads to changes in APP (amyloid precursor protein) trafficking mediated by LRP1 and SorLA. Cellular and molecular life sciences : CMLS 33 28799085
2013 The SORL1 gene and convergent neural risk for Alzheimer's disease across the human lifespan. Molecular psychiatry 32 24166411
2013 SORLA-mediated trafficking of TrkB enhances the response of neurons to BDNF. PloS one 30 23977241
2013 SORLA-dependent and -independent functions for PACS1 in control of amyloidogenic processes. Molecular and cellular biology 30 24001769
2021 Impaired SorLA maturation and trafficking as a new mechanism for SORL1 missense variants in Alzheimer disease. Acta neuropathologica communications 29 34922638
2015 Y682G Mutation of Amyloid Precursor Protein Promotes Endo-Lysosomal Dysfunction by Disrupting APP-SorLA Interaction. Frontiers in cellular neuroscience 29 25904844
2006 Pitavastatin attenuates the PDGF-induced LR11/uPA receptor-mediated migration of smooth muscle cells. Biochemical and biophysical research communications 29 16919601
2017 SORL1 Variants Show Different Association with Early-Onset and Late-Onset Alzheimer's Disease Risk. Journal of Alzheimer's disease : JAD 27 28527213
2016 SORL1 gene, plasma biomarkers, and the risk of Alzheimer's disease for the Han Chinese population in Taiwan. Alzheimer's research & therapy 27 28034305
2014 Influence of genetic variants in SORL1 gene on the manifestation of Alzheimer's disease. Neurobiology of aging 26 25659857
2012 SORL1 genetic variants and cerebrospinal fluid biomarkers of Alzheimer’s disease. European archives of psychiatry and clinical neuroscience 25 22286501
2012 Circulating soluble LR11/SorLA levels are highly increased and ameliorated by chemotherapy in acute leukemias. Clinica chimica acta; international journal of clinical chemistry 24 22750733
2016 Cytokine-Like Factor 1, an Essential Facilitator of Cardiotrophin-Like Cytokine:Ciliary Neurotrophic Factor Receptor α Signaling and sorLA-Mediated Turnover. Molecular and cellular biology 23 26858303
2014 Tetraspanin CD9 modulates ADAM17-mediated shedding of LR11 in leukocytes. Experimental & molecular medicine 23 24699135
2013 An updated meta-analysis of the association between SORL1 variants and the risk for sporadic Alzheimer's disease. Journal of Alzheimer's disease : JAD 23 23948893
2012 Interrelations between CSF soluble AβPPβ, amyloid-β 1-42, SORL1, and tau levels in Alzheimer's disease. Journal of Alzheimer's disease : JAD 23 22045485
1998 Developmental regulation of LR11 expression in murine brain. DNA and cell biology 23 9726247
2024 A familial missense variant in the Alzheimer's disease gene SORL1 impairs its maturation and endosomal sorting. Acta neuropathologica 22 38244079
2013 The soluble form of LR11 protein is a regulator of hypoxia-induced, urokinase-type plasminogen activator receptor (uPAR)-mediated adhesion of immature hematological cells. The Journal of biological chemistry 22 23486467
2021 A feed-forward loop between SorLA and HER3 determines heregulin response and neratinib resistance. Oncogene 21 33420373
2020 Soluble SORLA Enhances Neurite Outgrowth and Regeneration through Activation of the EGF Receptor/ERK Signaling Axis. The Journal of neuroscience : the official journal of the Society for Neuroscience 21 32601248
2012 Sortilin and SorLA regulate neuronal sorting of trophic and dementia-linked proteins. Molecular neurobiology 21 22297619
2009 Sequence variation in SORL1 and dementia risk in Swedes. Neurogenetics 21 19653016
2006 N-linked oligosaccharides on the low density lipoprotein receptor homolog SorLA/LR11 are modified with terminal GalNAc-4-SO4 in kidney and brain. The Journal of biological chemistry 21 17121844
2017 SorLA in Interleukin-6 Signaling and Turnover. Molecular and cellular biology 20 28265003
2023 Dimerization of the Alzheimer's disease pathogenic receptor SORLA regulates its association with retromer. Proceedings of the National Academy of Sciences of the United States of America 19 36652482
2023 Pharmacologic enhancement of retromer rescues endosomal pathology induced by defects in the Alzheimer's gene SORL1. Stem cell reports 19 37949073
2014 SORL1 gene polymorphism association with late-onset Alzheimer's disease. Neuroscience letters 19 25450149
2024 The SORL1 p.Y1816C variant causes impaired endosomal dimerization and autosomal dominant Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America 18 39226352

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