Affinage

SCARB1

Scavenger receptor class B member 1 · UniProt Q8WTV0

Length
552 aa
Mass
60.9 kDa
Annotated
2026-04-28
100 papers in source corpus 33 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SCARB1 encodes SR-BI, a multiligand cell-surface scavenger receptor that mediates selective, bidirectional transfer of cholesterol esters, vitamin E, and carotenoids between lipoproteins and cells through a hydrophobic tunnel traversing its extracellular domain (PMID:24162852, PMID:9539787, PMID:16380385, PMID:28465440). In the liver, SR-BI is the principal receptor for selective HDL cholesteryl ester uptake, with its surface abundance controlled by PDZK1-dependent posttranscriptional stabilization, Nedd4-1-mediated ubiquitination at K500/K508, RBFOX2-regulated alternative splicing, and assembly into negatively cooperative, leucine-zipper-stabilized plasma membrane clusters (PMID:15767854, PMID:37863040, PMID:36536133, PMID:31231038, PMID:21254782). In endothelial cells SR-BI drives LDL transcytosis by recruiting DOCK4 via an eight-amino-acid cytoplasmic motif to activate RAC1, while in macrophages it mediates efferocytosis through phosphatidylserine binding and Src/PI3K/Rac1 signaling and regulates autophagy via PPARα–TFEB transcription and VPS34–Beclin-1 complex recruitment (PMID:31019307, PMID:26059978, PMID:33661763). SR-BI also functions as a host entry factor for HCV and Plasmodium sporozoites and as a receptor for silica particles that triggers inflammasome activation (PMID:20949066, PMID:18779053, PMID:28147282).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1995 High

    Establishing SR-BI as a specific receptor for anionic phospholipids resolved the question of whether class B scavenger receptors could recognize non-lipoprotein lipid ligands, opening the broader concept of SR-BI as a multiligand receptor.

    Evidence Direct binding and competition assays in transfected cells measuring PS and PI binding with quantitative Kd

    PMID:7541795

    Open questions at the time
    • Physiological relevance of anionic phospholipid binding in vivo not tested
    • No structural insight into lipid recognition domain
  2. 1996 High

    Demonstrating that SR-BI mediates endocytosis of apoptotic cells established its role beyond lipid transport as a phagocytic receptor, presaging later efferocytosis studies.

    Evidence Gain-of-function CHO transfection with apoptotic cell and liposome uptake assays

    PMID:8549669

    Open questions at the time
    • Signaling pathway downstream of apoptotic cell recognition unknown
    • In vivo relevance to atherosclerosis not addressed
  3. 1998 High

    Quantitative metabolic tracing in SR-BI-attenuated mice proved that hepatic SR-BI is the dominant receptor for selective HDL cholesteryl ester clearance in vivo, establishing its central role in reverse cholesterol transport.

    Evidence SR-BI att mice with 53% reduced expression; nondegradable radiolabeled HDL tracing showing proportional reduction in hepatic CE uptake

    PMID:9539787

    Open questions at the time
    • Structural basis of selective CE uptake unknown
    • Whether SR-BI mediates whole-particle HDL uptake or only selective lipid transfer not resolved
  4. 2001 High

    Two studies defined SR-BI's membrane context: caveolin-1 acts as a negative regulator of SR-BI-mediated selective CE uptake, and SR-BI is required for microvillar channel formation in adrenocortical cells, linking receptor function to plasma membrane ultrastructure.

    Evidence Caveolin-1 overexpression in multiple cell lines inhibiting CE uptake; electron microscopy of SR-BI-null adrenal glands lacking microvillar channels

    PMID:11683884 PMID:11907136

    Open questions at the time
    • Molecular mechanism by which SR-BI organizes microvillar channels undefined
    • Whether caveolin-1 regulation occurs in hepatocytes in vivo not established
  5. 2003 High

    SR-BI was shown to deliver HDL-associated estradiol to endothelial eNOS and to serve as a receptor for hypochlorite-modified LDL, broadening the ligand repertoire beyond native lipoproteins and linking SR-BI to vascular signaling.

    Evidence SR-BI null mice lacking HDL-estradiol-mediated vasodilation; CHO overexpression with antibody blocking confirming HOCl-LDL recognition

    PMID:12750408 PMID:12968020

    Open questions at the time
    • Structural determinants of estradiol transfer not identified
    • Whether oxidized LDL binding uses the same tunnel as CE uptake unknown
  6. 2005 High

    PDZK1 was identified as a PDZ-domain adaptor essential for hepatic SR-BI protein stability, and SR-BI was shown to mediate intestinal vitamin E and lipid absorption, extending its physiological role to the gut.

    Evidence PDZK1 KO mice with near-complete hepatic SR-BI protein loss despite normal mRNA; Caco-2 blocking and intestinal SR-BI transgenic mice for vitamin E uptake

    PMID:15767854 PMID:16380385

    Open questions at the time
    • Mechanism by which PDZK1 prevents SR-BI degradation not resolved
    • Whether intestinal SR-BI operates via the same selective uptake mechanism as hepatic SR-BI unclear
  7. 2006 High

    Kinetic studies demonstrated that the vast majority of SR-BI-mediated selective CE uptake occurs at the cell surface rather than via retroendocytosis, refining the mechanistic model of lipid transfer.

    Evidence Pulse-chase assay with biotinylated 125I-HDL3 showing HDL resecretion rate >30-fold slower than selective CE uptake

    PMID:16705213

    Open questions at the time
    • Whether surface-based transfer requires specific membrane domains not fully resolved
    • Structural basis of surface transfer mechanism unknown at this point
  8. 2008 High

    SR-BI was linked to innate immunity and infection: it supplies adrenal cholesterol for glucocorticoid synthesis during endotoxemia and clears hepatic LPS, and it serves as a dual host factor for Plasmodium liver invasion and intracellular development.

    Evidence SR-BI null mice with lethal endotoxic shock rescued by corticosterone; RNAi + overexpression + heterozygous mice for Plasmodium infection

    PMID:18064300 PMID:18779053

    Open questions at the time
    • Molecular mechanism of LPS clearance by SR-BI not defined
    • Whether Plasmodium exploits lipid transfer function or a separate binding site unresolved
  9. 2011 High

    Rigorous binding analysis established that SR-BI exhibits negatively cooperative HDL binding, implying functional receptor oligomerization at the membrane and explaining complex binding kinetics observed in earlier studies.

    Evidence Radiolabeled HDL binding with Scatchard analysis and infinite dilution dissociation rate method confirming negative cooperativity

    PMID:21254782

    Open questions at the time
    • Stoichiometry and structural arrangement of SR-BI oligomers unknown
    • Whether negative cooperativity extends to all ligand classes not tested
  10. 2012 High

    SR-BI in extraembryonic tissues was shown to mediate maternal-to-fetal cholesterol and later vitamin E transport required for neural tube closure, establishing a developmental role.

    Evidence SR-BI null embryos with exencephaly and reduced cholesterol; dietary vitamin E supplementation rescuing NTDs from 54% to 2%

    PMID:23221804 PMID:28701710

    Open questions at the time
    • Whether SR-BI transports other essential lipids during embryogenesis not examined
    • Human relevance of this developmental phenotype not established
  11. 2013 High

    Homology modeling from the LIMP-2 crystal structure combined with SR-BI mutagenesis revealed a hydrophobic tunnel traversing the extracellular domain through which cholesterol esters are transferred from lipoprotein to the plasma membrane, providing the first structural explanation for selective lipid uptake.

    Evidence LIMP-2 crystal structure; SR-BI homology model; tunnel-disrupting mutations abolishing CE uptake

    PMID:24162852

    Open questions at the time
    • No direct SR-BI crystal structure available
    • Dynamics of lipid transit through the tunnel not characterized
    • Whether all lipid ligands use the same tunnel unresolved
  12. 2015 High

    Mechanistic dissection of macrophage efferocytosis showed that SR-BI binds phosphatidylserine on apoptotic cells and signals through Src→PI3K→Rac1 to drive engulfment, with SR-BI hematopoietic deficiency causing increased atherosclerotic necrosis in vivo.

    Evidence SR-BI KO macrophages with pharmacological Src/PI3K/Rac1 inhibition; bone marrow transplantation in ApoE−/− and LDLR−/− mice

    PMID:26059978

    Open questions at the time
    • Whether SR-BI efferocytosis and lipid uptake functions are structurally separable unknown
    • Identity of co-receptors in efferocytosis signaling not defined
  13. 2017 High

    Multiple discoveries in 2017 revealed that endothelial SR-BI drives LDL transcytosis via DOCK4/RAC1 recruitment to its cytoplasmic tail promoting atherosclerosis, that SR-BI recognizes silica through an extracellular α-helix triggering inflammasome activation, and that SR-BI mediates carotenoid uptake and dynamin-dependent HDL transcytosis across brain endothelium.

    Evidence Domain mutagenesis and DOCK4 interaction in endothelial monolayers; expression cloning and SR-BI KO for silica recognition; functional assays with WT vs. exon-4-deleted SCARB1 for carotenoid uptake; siRNA and pharmacological inhibitor panel for brain endothelial HDL transcytosis

    PMID:28147282 PMID:28465440 PMID:29163190 PMID:31019307

    Open questions at the time
    • Whether DOCK4-dependent transcytosis pathway operates in brain endothelium not tested
    • Crystal structure of SR-BI silica-binding helix not determined
    • Mechanism of carotenoid transfer through the tunnel not characterized
  14. 2019 High

    Single-molecule imaging revealed that SR-BI forms large metastable clusters at the plasma membrane via a C-terminal leucine zipper, and that multimerization prevents internalization and is essential for receptor function, unifying earlier observations of negative cooperativity and surface-based lipid transfer.

    Evidence Single-chain antibody live-cell imaging; single-molecule tracking; leucine zipper mutagenesis causing rapid internalization

    PMID:31231038

    Open questions at the time
    • Precise oligomeric stoichiometry not determined
    • How PDZK1 binding interfaces with cluster formation not resolved
  15. 2019 High

    HMGB1 nuclear translocation triggered by LDL requires SR-BI in endothelial cells, creating a positive feedback loop where HMGB1 stabilizes SREBP2 to increase SR-BI expression and sustain LDL transcytosis.

    Evidence siRNA knockdown, TIRF microscopy, endothelial HMGB1 KO mice with aortic LDL accumulation measurements

    PMID:33054399

    Open questions at the time
    • Whether this feedback loop operates in non-endothelial cells unknown
    • Direct physical interaction between HMGB1 and SR-BI not demonstrated
  16. 2021 High

    SR-BI was discovered to regulate macrophage autophagy through two mechanisms—PPARα-dependent TFEB transcription and direct recruitment of VPS34–Beclin-1 to autophagosomal cholesterol domains—explaining how SR-BI deficiency promotes foam cell formation and apoptosis.

    Evidence SR-BI KO macrophages; co-IP of VPS34–Beclin-1; VPS34 activity assays; Tfeb and Vps34 overexpression rescue

    PMID:33661763

    Open questions at the time
    • Whether autophagy regulation is specific to macrophages or general unknown
    • How SR-BI cholesterol domains are organized on autophagosomes not structurally resolved
  17. 2022 High

    RBFOX2-dependent alternative splicing of Scarb1 in the liver was identified as a regulatory layer altered in obesity, with splice-switching oligonucleotides rescuing hepatic lipid homeostasis, revealing a post-transcriptional control axis distinct from PDZK1-mediated protein stabilization.

    Evidence Enhanced iCLIP of RBFOX2 in mouse liver; RBFOX2 conditional KO; splice-switching oligonucleotides correcting Scarb1 isoform ratio

    PMID:36536133

    Open questions at the time
    • Functional difference between Scarb1 splice isoforms not fully characterized
    • Whether RBFOX2-mediated splicing is conserved in human liver not confirmed
  18. 2023 High

    Two studies refined SR-BI regulation: Nedd4-1 ubiquitinates SR-BI at K500/K508 to promote its degradation (counteracted by lipocalin-2), and intestinal FXR–bile acid signaling drives SR-BI expression in enterocytes to regulate chylomicron secretion.

    Evidence K500A/K508A knock-in mice and hepatocyte Lcn2 KO/OE for ubiquitination; intestinal SR-BI KO and FMT with bile acid quantification for FXR regulation

    PMID:37160898 PMID:37863040

    Open questions at the time
    • Whether other E3 ligases also target SR-BI unresolved
    • How ubiquitination at K500/K508 interfaces with leucine zipper-mediated clustering unknown
    • Whether FXR-driven intestinal SR-BI regulation affects systemic vitamin E status not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution crystal or cryo-EM structure of SR-BI itself—rather than a LIMP-2-based homology model—is needed to define the lipid tunnel geometry, explain ligand selectivity, and map the silica-binding and PS-binding interfaces.
  • No experimental SR-BI structure available
  • Structural basis of negative cooperativity and leucine zipper-mediated clustering unresolved
  • Whether the DOCK4-binding cytoplasmic motif and PDZK1-binding C-terminus create allosteric cross-talk is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 5 GO:0038024 cargo receptor activity 5 GO:0008289 lipid binding 4 GO:0060090 molecular adaptor activity 2
Localization
GO:0005886 plasma membrane 5 GO:0031410 cytoplasmic vesicle 3
Pathway
R-HSA-1430728 Metabolism 6 R-HSA-382551 Transport of small molecules 5 R-HSA-168256 Immune System 3 R-HSA-1643685 Disease 2 R-HSA-9612973 Autophagy 1
Partners
BECN1CAV1DOCK4NEDD4PDZK1RAC1RBFOX2VPS34

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 SR-BI (and CD36) are specific cell surface receptors for anionic phospholipids (phosphatidylserine and phosphatidylinositol), demonstrated by direct binding and ligand competition assays in transfected cells; PS liposome binding Kd ~15 µg phospholipid/ml. Direct binding and ligand competition assays in transfected cells The Journal of biological chemistry High 7541795
1996 SR-BI (SRB1) recognizes and mediates endocytosis of apoptotic cells as well as negatively charged liposomes, demonstrated in CHO transfectants constitutively expressing SRB1. CHO cell transfection, uptake assays with apoptotic cells and negatively charged liposomes Experimental cell research High 8549669
1998 Hepatic SR-BI is the major mediator of selective cholesterol ester (CE) uptake from HDL in vivo; mice with 53% reduced hepatic SR-BI expression showed 47% decrease in selective CE uptake by liver and 53% reduction in selective removal of HDL-CE from plasma, with corresponding 50–70% increase in plasma HDL cholesterol. Targeted promoter mutation (SR-BI att mice), metabolic studies with nondegradable radiolabeled HDL Proceedings of the National Academy of Sciences of the United States of America High 9539787
2001 SR-BI is predominantly associated with caveolae in CHO cells; overexpression of caveolin-1 inhibited SR-BI-dependent selective HDL cholesteryl ester uptake by 50–60% without altering HDL cell association, establishing caveolin-1 as a negative regulator of SR-BI-mediated selective CE uptake. Stable transfection of caveolin-1 in RAW/J774 cells and SR-BI CHO cells; adenoviral caveolin-1 overexpression; beta-cyclodextrin depletion experiments European journal of biochemistry High 11683884
2001 SR-BI is required for microvillar channel formation in adrenocortical cells in vivo; SR-BI-null mice lack microvillar channels and have thinner microvillar membranes, demonstrating SR-BI's role in plasma membrane ultrastructure organization. Electron microscopy comparison of Srb1+/+ and Srb1-/- mouse adrenal glands Journal of lipid research High 11907136
2003 HDL-associated estradiol stimulates endothelial NO synthase (eNOS) and promotes vasodilation in an SR-BI-dependent manner; this effect was absent in SR-BI null mice and required SR-BI for HDL-mediated estrogen delivery to eNOS. Ovariectomized and estrogen replacement mouse models; SR-BI null mice; vascular muscle strip relaxation assays The Journal of clinical investigation High 12750408
2003 SR-BI and CD36 are receptors for hypochlorite-modified LDL (HOCl-LDL); recognition is mediated by the protein moiety of HOCl-LDL, demonstrated by specific binding to CHO cells overexpressing CD36 and SR-BI and blocking by specific antibodies. Binding and competition assays in CHO cells overexpressing SR-BI or CD36; blocking antibody experiments; dynamic light scattering The Journal of biological chemistry High 12968020
2004 SR-BI localizes to membrane rafts devoid of caveolin-1 in HepG2 hepatoma cells; perturbation of membrane raft structure differentially affects LDL-CE and HDL-CE selective uptake; both LDL- and HDL-CE selective uptake occur via a retroendocytic pathway in HepG2 cells. Detergent-free sucrose gradient fractionation; cholesterol oxidase, sphingomyelinase, filipin, and beta-cyclodextrin treatment; retroendocytosis assays Journal of cell science High 15226391
2005 SR-BI mediates vitamin E (alpha- and gamma-tocopherol) intestinal absorption; anti-SR-BI antibodies and BLT-1 (SR-BI inhibitor) blocked up to 80% of vitamin E uptake in Caco-2 cells; SR-BI overexpression in mouse intestine increased gamma-tocopherol bioavailability 2.7-fold. Caco-2 TC-7 cell monolayer assays with antibody/inhibitor blocking; transgenic mice overexpressing intestinal SR-BI The Journal of biological chemistry High 16380385
2005 PDZK1 is a PDZ-domain adaptor protein that binds to the C-terminal cytoplasmic tail of SR-BI and controls its activity via a tissue-specific posttranscriptional mechanism; PDZK1-deficient mice display near-complete hepatic ablation of SR-BI protein despite normal SR-BI mRNA, resulting in elevated plasma cholesterol. PDZK1 knockout mice; hepatic SR-BI protein and mRNA analysis Current opinion in lipidology High 15767854
2006 SR-BI-mediated HDL retroendocytosis contributes minimally to selective CE uptake; the vast majority of SR-BI-dependent selective CE uptake occurs at the cell surface in both COS-7 and HepG2 cells, as HDL resecretion rate is >30-fold slower than selective CE uptake rate. Pulse-chase assay with biotinylated 125I-HDL3; quantitative measurement of HDL uptake and resecretion in SR-BI-expressing cells Journal of lipid research High 16705213
2006 Intestinal SR-BI overexpression accelerates absorption of both cholesterol and triglycerides in vivo, demonstrating SR-BI's functional role in intestinal lipid absorption. Transgenic mice overexpressing SR-BI in intestine; 14C-cholesterol and 3H-triolein absorption assays The Journal of biological chemistry High 16421100
2007 Macrophage SR-BI does not contribute to macrophage reverse cholesterol transport in vivo (unlike ABCA1 and ABCG1), demonstrated using SR-BI-deficient primary macrophages in an in vivo RCT assay. In vivo macrophage RCT assay using SR-BI-deficient primary macrophages transplanted into mice The Journal of clinical investigation High 17657311
2008 SR-BI is required for the antiinflammatory response to LPS-induced endotoxic shock through two mechanisms: (1) facilitating HDL cholesterol delivery to the adrenal gland for glucocorticoid synthesis (primary adrenal malfunction in SR-BI-null mice), and (2) mediating hepatic clearance of LPS. SR-BI-null mouse model; LPS and ACTH challenge; corticosterone supplementation rescue experiments; LPS plasma clearance assays The Journal of clinical investigation High 18064300
2008 SR-BI plays a dual role in Plasmodium liver infection: affecting both sporozoite invasion and intracellular parasite development; RNAi-mediated SR-BI silencing reduced P. berghei and P. falciparum infection in cell lines and in vivo. RNAi screening in Huh7 cells; SR-BI overexpression; in vivo silencing in mice; SR-BI(+/-) heterozygous mouse model; inhibition of SR-BI in human primary hepatocytes Cell host & microbe High 18779053
2010 PDZK1 interaction with the C-terminal cytoplasmic tail of SR-BI (specifically the final amino acid) is required for SR-BI's role in HCV entry; overexpression of the SR-BI C-terminal cytoplasmic tail (aa 479-509) but not a truncation lacking the last residue competed with PDZK1 and reduced HCV infection. Stable shRNA knockdown of PDZK1 in Huh-7 cells; GFP-tagged SR-BI C-terminus constructs; Co-IP/interaction assays; HCV infection susceptibility assays PLoS pathogens High 20949066
2011 SR-BI facilitates bidirectional cholesterol flux in macrophages (both efflux and influx from HDL) in non-lipid-loaded cells; SR-BI is present both on the cell surface and intracellularly; HDL CE selective uptake in bone marrow-derived macrophages is not SR-BI-dependent. Mouse bone marrow-derived macrophage culture; cholesterol efflux and influx assays; SR-BI-null macrophages Atherosclerosis Medium 21481393
2012 SR-BI mediates efferocytosis in macrophages via binding phosphatidylserine on apoptotic cells, triggering Src phosphorylation and membrane recruitment, leading to downstream PI3K and Rac1 activation for engulfment; SR-BI deficiency in hematopoietic cells causes severely defective efferocytosis and increased atherosclerotic lesion necrosis. Bone marrow transplantation in ApoE-/- and LDLR-/- mice; pharmacological inhibition of Src, PI3K, Rac1; SR-BI-/- macrophage efferocytosis assays in vitro and in vivo Journal of lipid research High 26059978
2013 Crystal structure of LIMP-2 informed homology modeling of SR-BI; mutagenesis of SR-BI revealed a tunnel (cavity) traversing the entire molecule through which cholesterol esters are delivered from bound lipoprotein to the outer leaflet of the plasma membrane, accounting for selective lipid transfer. Crystal structure of LIMP-2; homology modelling of SR-BI; SR-BI mutagenesis with functional CE uptake assays Nature High 24162852
2017 SR-B1 in endothelial cells mediates LDL transcytosis via direct LDL binding and an eight-amino-acid cytoplasmic domain that recruits the guanine nucleotide exchange factor DOCK4; DOCK4 couples LDL binding to SR-B1 with RAC1 activation for receptor internalization and LDL transport across the endothelium, promoting atherosclerosis. In vivo mouse studies; LDL co-localization with SR-B1 in endothelial vesicles; domain mutagenesis; DOCK4 interaction (recruitment assays); RAC1 activation assays; endothelial monolayer transcytosis assays Nature High 31019307
2017 SR-B1 is a silica receptor; through an extracellular alpha-helix, SR-B1 specifically recognizes amorphous and crystalline silica; SR-B1-mediated silica recognition is associated with caspase-1-mediated inflammasome activation in macrophages and monocytes. Functional expression cloning; SR-B1 genetic deletion and monoclonal antibody masking; caspase-1 activation assays in mouse macrophages and human PBMCs; in vivo pulmonary inflammation model Cell reports High 28147282
2017 SCARB1 is required for carotenoid uptake in birds; wild-type SCARB1 promotes cellular uptake of carotenoids, while a mutant isoform lacking exon 4 (due to splice donor site mutation) loses this function, causing absence of carotenoid coloration. Genetic mapping; biochemical analysis of carotenoids in tissues; functional uptake assays comparing wild-type and mutant SCARB1 isoforms Proceedings of the National Academy of Sciences of the United States of America High 28465440
2017 SR-BI mediates HDL transcytosis across brain microvascular endothelial cells in a dynamin-dependent but clathrin-, caveolin-, and PDZK1-independent manner; SR-BI knockdown significantly attenuated HDL internalization, and eNOS inhibition increased HDL internalization. Spinning-disc confocal and TIRF microscopy; siRNA knockdown of SR-BI, caveolin-1, PDZK1, clathrin heavy chain; pharmacological inhibition of eNOS and NO manipulation Frontiers in physiology High 29163190
2019 SR-B1 undergoes multimerization into large metastable clusters at the plasma membrane through its C-terminal leucine zipper domain; multimerization prevents receptor internalization and is required for plasmalemmal retention and SR-B1 function; disrupting actin polymerization or mutating the leucine zipper impairs multimerization and causes rapid internalization. Single-chain variable fragment (ScFv) antibody for live-cell imaging; single-molecule tracking; C-terminal domain mutagenesis; actin disruption experiments; sucrose density gradient fractionation Developmental cell High 31231038
2019 LDL-induced nuclear translocation of endothelial HMGB1 requires SR-BI; endothelial HMGB1 regulates LDL transcytosis by prolonging the half-life of SREBP2, which drives SR-BI expression, forming a positive feedback loop. siRNA knockdown; TIRF microscopy for LDL transcytosis measurement; HMGB1 overexpression; inhibitor studies; SREBP2 half-life measurements; endothelial-specific HMGB1 KO mice with aortic LDL accumulation assay Arteriosclerosis, thrombosis, and vascular biology High 33054399
2020 Macrophage SR-BI deficiency reduces free cholesterol-induced macrophage apoptosis through upregulation of apoptosis inhibitor of macrophage (AIM); AIM protects SR-BI-deficient macrophages from free cholesterol-induced apoptosis, promoting atherosclerotic plaque growth. Macrophage-specific SR-BI KO mice (Lysm-Cre x SR-B1f/f); bone marrow transplantation into Ldlr-/- mice; in vitro free cholesterol-induced apoptosis assays; AIM expression analysis Cardiovascular research High 31119270
2021 Macrophage SR-BI regulates autophagy by: (1) enhancing PPARα-dependent TFEB transcription, and (2) localizing to autophagosomes where it forms cholesterol domains and recruits the VPS34-Beclin-1 complex; SR-BI deficiency reduces VPS34 activity and autophagy, increasing foam cell formation and apoptosis. SR-BI KO macrophages; atherosclerotic aorta analysis; PPARα/TFEB pathway dissection; co-immunoprecipitation of VPS34-Beclin-1 with SR-BI; VPS34 activity assays; Tfeb and Vps34 overexpression rescue experiments The Journal of clinical investigation High 33661763
2022 The RNA splicing factor RBFOX2 regulates Scarb1 alternative splicing in the liver; decreased RBFOX2 function in diet-induced obesity causes a Scarb1 isoform switch that alters hepatocyte lipid homeostasis; splice-switching oligonucleotides targeting this network alleviate obesity-induced liver inflammation. Enhanced iCLIP of RBFOX2 in mouse liver; RBFOX2 conditional KO; splice-switching oligonucleotides; lipoprotein profiling Nature metabolism High 36536133
2023 Hepatocyte lipocalin-2 (Lcn2) regulates hepatic SR-BI by blocking Nedd4-1-mediated SR-BI ubiquitination at K500 and K508, thereby preventing SR-BI degradation and improving HDL metabolism and alleviating atherogenesis. Hepatocyte-specific Lcn2 OE and KO mice; Nedd4-1 and SR-BI deletion mice; SR-BI K500A/K508A knock-in mutation mice; ubiquitination assays; HDL metabolic studies Developmental cell High 37863040
2023 Intestinal FXR activation by bile acids (chenodeoxycholic acid) stimulates SR-B1 expression in enterocytes; resveratrol intervention represses jejunal SR-B1 via gut microbiome-dependent reduction of bile acid levels and FXR activity, thereby inhibiting chylomicron secretion. Intestinal mucosa-specific SR-B1-/- mice; fecal microbiota transplantation; Caco-2 cell treatment; bile acid quantification; chylomicron secretion assays Nature communications High 37160898
2011 SR-BI exhibits negatively cooperative binding of HDL (and LDL); Scatchard and nonlinear least-squares analysis of 125I-HDL binding across an expanded ligand concentration range demonstrated two independent binding site classes or negative cooperativity, ruled out by the infinite dilution dissociation rate method which confirmed negative cooperativity. Radiolabeled HDL binding assays; Scatchard analysis; infinite dilution dissociation rate method; nonlinear least-squares model fitting Biochemistry High 21254782
2012 SR-BI null mice exhibit high prevalence of exencephaly in embryos, associated with reduced cholesterol content in SR-BI-/- embryos; SR-BI is expressed in extraembryonic tissues (parietal yolk sac trophoblast cells) and mediates maternal-fetal cholesterol transport required for neural tube closure. SR-BI-null mouse intercrosses; embryo cholesterol measurement; immunolocalization of SR-BI in extraembryonic tissues; embryonic phenotype analysis Human molecular genetics High 23221804
2017 SR-BI in yolk sac trophoblast giant cells mediates maternal provision of vitamin E to the embryo during neural tube closure; SR-BI-/- embryos have very low vitamin E content; maternal alpha-tocopherol supplementation prevented neural tube defects in SR-BI-/- embryos from 54% to 2%. SR-BI-/- mouse model; embryonic vitamin E measurement; ROS measurements; dietary supplementation rescue; gene expression analysis (Pax3, Alx1, Alx3) Scientific reports High 28701710

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 The class B scavenger receptors SR-BI and CD36 are receptors for anionic phospholipids. The Journal of biological chemistry 485 7541795
2007 Macrophage ABCA1 and ABCG1, but not SR-BI, promote macrophage reverse cholesterol transport in vivo. The Journal of clinical investigation 478 17657311
2017 SR-B1: A Unique Multifunctional Receptor for Cholesterol Influx and Efflux. Annual review of physiology 310 29125794
2006 Role of apoA-I, ABCA1, LCAT, and SR-BI in the biogenesis of HDL. Journal of molecular medicine (Berlin, Germany) 297 16501936
1998 Targeted mutation reveals a central role for SR-BI in hepatic selective uptake of high density lipoprotein cholesterol. Proceedings of the National Academy of Sciences of the United States of America 263 9539787
2019 SR-B1 drives endothelial cell LDL transcytosis via DOCK4 to promote atherosclerosis. Nature 261 31019307
2013 Structure of LIMP-2 provides functional insights with implications for SR-BI and CD36. Nature 242 24162852
1996 CLA1, a novel gene required for chloroplast development, is highly conserved in evolution. The Plant journal : for cell and molecular biology 224 8653115
2005 Scavenger receptor class B type I (SR-BI) is involved in vitamin E transport across the enterocyte. The Journal of biological chemistry 195 16380385
2005 Differential effects of HDL subpopulations on cellular ABCA1- and SR-BI-mediated cholesterol efflux. Journal of lipid research 193 16061948
2017 SR-BI: A Multifunctional Receptor in Cholesterol Homeostasis and Atherosclerosis. Trends in endocrinology and metabolism: TEM 162 28259375
2000 The role of the high-density lipoprotein receptor SR-BI in cholesterol metabolism. Current opinion in lipidology 157 10787173
2008 SR-BI protects against endotoxemia in mice through its roles in glucocorticoid production and hepatic clearance. The Journal of clinical investigation 131 18064300
1996 SRB1, a class B scavenger receptor, recognizes both negatively charged liposomes and apoptotic cells. Experimental cell research 130 8549669
2008 Host scavenger receptor SR-BI plays a dual role in the establishment of malaria parasite liver infection. Cell host & microbe 128 18779053
2003 HDL-associated estradiol stimulates endothelial NO synthase and vasodilation in an SR-BI-dependent manner. The Journal of clinical investigation 125 12750408
2004 The role of scavenger receptor class B type I (SR-BI) in lipid trafficking. defining the rules for lipid traders. The international journal of biochemistry & cell biology 120 14592533
2015 Macrophage SR-BI mediates efferocytosis via Src/PI3K/Rac1 signaling and reduces atherosclerotic lesion necrosis. Journal of lipid research 117 26059978
2016 Targeting the SR-B1 Receptor as a Gateway for Cancer Therapy and Imaging. Frontiers in pharmacology 108 28018216
2017 SR-BI Mediated Transcytosis of HDL in Brain Microvascular Endothelial Cells Is Independent of Caveolin, Clathrin, and PDZK1. Frontiers in physiology 101 29163190
2006 Accelerated lipid absorption in mice overexpressing intestinal SR-BI. The Journal of biological chemistry 100 16421100
2017 High-density lipoprotein receptor SCARB1 is required for carotenoid coloration in birds. Proceedings of the National Academy of Sciences of the United States of America 94 28465440
2017 SR-B1 Is a Silica Receptor that Mediates Canonical Inflammasome Activation. Cell reports 88 28147282
2004 Localization and regulation of SR-BI in membrane rafts of HepG2 cells. Journal of cell science 81 15226391
2001 Role of scavenger receptors SR-BI and CD36 in selective sterol uptake in the small intestine. Biochemistry 75 11560515
2021 Macrophage SR-BI modulates autophagy via VPS34 complex and PPARα transcription of Tfeb in atherosclerosis. The Journal of clinical investigation 64 33661763
2001 Caveolin-1 negatively regulates SR-BI mediated selective uptake of high-density lipoprotein-derived cholesteryl ester. European journal of biochemistry 64 11683884
2003 Class B scavenger receptors CD36 and SR-BI are receptors for hypochlorite-modified low density lipoprotein. The Journal of biological chemistry 62 12968020
2012 Macrophage SR-BI regulates LPS-induced pro-inflammatory signaling in mice and isolated macrophages. Journal of lipid research 59 22589557
1999 Influence of the HDL receptor SR-BI on atherosclerosis. Current opinion in lipidology 59 10680042
2011 Scavenger receptor SR-BI in macrophage lipid metabolism. Atherosclerosis 57 21481393
2004 Population-based study of SR-BI genetic variation and lipid profile. Atherosclerosis 56 15186961
2014 Rutaecarpine suppresses atherosclerosis in ApoE-/- mice through upregulating ABCA1 and SR-BI within RCT. Journal of lipid research 55 24908654
2007 Cellular SR-BI and ABCA1-mediated cholesterol efflux are gender-specific in healthy subjects. Journal of lipid research 52 18057374
2002 SR-BI is required for microvillar channel formation and the localization of HDL particles to the surface of adrenocortical cells in vivo. Journal of lipid research 49 11907136
2004 Ontogeny, immunolocalisation, distribution and function of SR-BI in the human intestine. Journal of cell science 47 14676281
2009 rs5888 variant of SCARB1 gene is a possible susceptibility factor for age-related macular degeneration. PloS one 46 19806217
2010 The SR-BI partner PDZK1 facilitates hepatitis C virus entry. PLoS pathogens 45 20949066
2005 Regulation of SR-BI-mediated high-density lipoprotein metabolism by the tissue-specific adaptor protein PDZK1. Current opinion in lipidology 42 15767854
2016 Targeting SR-BI for Cancer Diagnostics, Imaging and Therapy. Frontiers in pharmacology 41 27729859
2009 Hepatic SR-BI, not endothelial lipase, expression determines biliary cholesterol secretion in mice. Journal of lipid research 40 19252221
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2013 Upregulation of caveolin-1 and SR-B1 in mice with non-alcoholic fatty liver disease. Hepatobiliary & pancreatic diseases international : HBPD INT 36 24322749
2007 Severely altered cholesterol homeostasis in macrophages lacking apoE and SR-BI. Journal of lipid research 36 17299204
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2011 Intestinal SR-BI is upregulated in insulin-resistant states and is associated with overproduction of intestinal apoB48-containing lipoproteins. American journal of physiology. Gastrointestinal and liver physiology 34 21546579
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2014 Identification of conserved residues in hepatitis C virus envelope glycoprotein E2 that modulate virus dependence on CD81 and SRB1 entry factors. Journal of virology 29 24990994
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2019 Loss of SR-BI Down-Regulates MITF and Suppresses Extracellular Vesicle Release in Human Melanoma. International journal of molecular sciences 15 30823658