• The clearance of the FVIIIa heterodimer was inhibited by the alpha-2-macroglobulin receptor-associated protein (RAP), which is a universal ligand of the LDLR family. (nih.gov)
  • Other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement. (embl.de)
  • We recently demonstrated that low-density lipoprotein receptor-related protein 1 (LRP1) is required for cardiovascular development in zebrafish. (nih.gov)
  • Moreover, LRP1 knockdown results in increased PARP-1 activity and subsequent phosphorylation of both retinoblastoma protein and cyclin-dependent kinase 2, which function to promote cell cycle progression and angiogenesis. (nih.gov)
  • In experiments in cells and mice, blocking a protein called LRP1 stopped both normal and harmful forms of tau from spreading between neurons. (nih.gov)
  • Blocking LRP1 also stopped the uptake of a disease-related mutant form of tau as well as small clumps of tau, which form prior to the development of tau tangles. (nih.gov)
  • The team next identified two different parts of the tau protein that could bind to LRP1 and trigger the uptake of tau into cells. (nih.gov)
  • LRP1 performs many functions in the brain, so targeting the receptor directly wouldn't likely be a practical approach for developing drugs to block the spread of tau. (nih.gov)
  • Among the genes containing nonsense mutations were the zinc finger protein-coding gene ZNF480, the karyopherin alpha 1 gene KPNA1, the low-density lipoprotein receptor-related gene LRP1, and the ALS-like protein-coding gene ALS2CL. (genomeweb.com)
  • Studies have suggested that the deletion of LDL receptor-related protein 1 (LRP1) in adult neurons or glial cells could be beneficial and promote neuronal health. (uky.edu)
  • It may function to prevent ligand binding of receptors during protein processing events within endosomal compartments. (harvard.edu)
  • Versatility in ligand recognition by LDL receptor family proteins: advances and frontiers. (harvard.edu)
  • Structure of an LDLR-RAP complex reveals a general mode for ligand recognition by lipoprotein receptors. (harvard.edu)
  • The kinetics of human amyloid-β (hAβ) 40 were examined in the rat pursuant to intravenous and intracerebroventricular administration after pretreatment with calcitriol, the active vitamin D receptor ligand (6.4 nmol·kg −1 in 0.3 ml corn oil every other day for four intraperitoneal doses) to induce P-glycoprotein (P-gp) and enhance hAβ 40 brain efflux. (aspetjournals.org)
  • Specifically, it is unclear whether APP acts as a receptor, and if so what its ligand(s) may be. (elifesciences.org)
  • In order to be internalized, the receptor-ligand complex must first cluster into clathrin-coated pits. (embl.de)
  • 2011). but suppresses osteoclastic activities by inhibiting the receptor activator of nuclear factor-kappa B (RANK)/receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) system, nuclear factor-kappa B (NF-B), mitogen-activated protein kinase (MAPK), and calcium signaling cascades. (eprf.ca)
  • Low-density lipoprotein receptor-related protein 8 (LRP8), also known as apolipoprotein E receptor 2 (ApoER2), is a protein that in humans is encoded by the LRP8 gene. (wikipedia.org)
  • The RELN receptors apolipoprotein E receptor 2 (ApoER2) and very low-density lipoprotein receptor (VLDLR) are involved in lipid metabolism and expressed in the hypothalamus. (elsevierpure.com)
  • Reelin is a glycoprotein that is mainly secreted by Cajal-Retzius neurons in the marginal zone, playing essential roles in the formation of the layered neocortex via its receptors, apolipoprotein E receptor 2 (ApoER2) and very low density lipoprotein receptor (VLDLR). (elsevierpure.com)
  • These receptors function in signal transduction and endocytosis of specific ligands. (wikipedia.org)
  • This motif is important for binding intracellular adapter proteins and endocytosis. (wikipedia.org)
  • It is also speculated that this insert may diminish the function of ApoER2 in lipoprotein endocytosis by somehow disrupting the NPXY motif. (wikipedia.org)
  • Because mice lacking the gene for LRP2 exhibit a deficiency of proximal tubule reabsorption and a significant reduction of the number and size of organelles associated with endocytosis in the proximal tubule [ 9 ], LRP2 is thought to play central roles in reabsorption of proteins and endocytosis. (biomedcentral.com)
  • The receptor helps move its ligands from the cell surface into the cell (endocytosis), and is also involved in transporting the ligands of a related receptor called cubulin. (medlineplus.gov)
  • The LDL receptor binds LDL and transports it into cells by acidic endocytosis. (embl.de)
  • For example, retrograde vesicular transport from the Golgi to the ER is needed to retrieve resident ER proteins that have escaped from this compartment ( 25 ), and endocytosis can transport proteins from the cell surface to the TGN ( 2 ), which is the cellular location where the secretory and endocytic pathways converge ( 31 ). (rupress.org)
  • Binds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. (cusabio.com)
  • It binds the PSD-95 adapter protein, cross-linking ApoER2 and the NMDA receptors during the process of long-term potentiation, and is also bound specifically by JIP-2, an important interaction in the JNK signalling pathway. (wikipedia.org)
  • A membrane protein found in the rough endoplasm reticulum (ENDOPLASMIC RETICULUM, ROUGH) that binds to LDL-RECEPTOR RELATED PROTEINS. (harvard.edu)
  • The first of these is the canonical Wnt/β-catenin pathway ( 5 ), in which Wnt3a, a member of the Wnt ligands, binds to a frizzled receptor and the corresponding co-receptor of low-density lipoprotein receptor-related protein 6 (LRP6). (spandidos-publications.com)
  • It was shown previously that the low-density lipoprotein receptor-related protein (LRP), a member of the low-density lipoprotein receptor (LDLR) family, binds to coagulation factor VIII (FVIII) in vitro. (nih.gov)
  • We show that APP binds the Wnt ligands Wnt3a and Wnt5a and that this binding regulates APP protein levels. (elifesciences.org)
  • ER resident proteins contain a retrieval signal, the COOH-terminal tetrapeptide Lys-Asp-Glu-Leu (KDEL), 1 which binds to a membrane receptor in the cis -Golgi region and returns them to the ER. (rupress.org)
  • Binding to lipid and heparan sulfate proteoglycans (HSPG) induces apoE to adopt active conformations for binding to low-density lipoprotein receptor (LDLR) family. (nih.gov)
  • This confirmed that the faster clearance of the FVIIIa heterodimer involves a receptor(s) from the LDLR family, likely LRP. (nih.gov)
  • The low-density lipoprotein receptor (LDLR) is the major cholesterol-carrying lipoprotein of plasma, acting to regulate cholesterol homeostasis in mammalian cells. (embl.de)
  • This interaction with the two receptors activates intracellular processes that begin with the phosphorylation of Dab1, a tyrosine kinase phosphorylated protein which is encoded by the DAB1 gene. (wikipedia.org)
  • PI3K activation leads to inhibitory phosphorylation of the tau kinase glycogen synthase kinase 3 beta (GSK3B), which alters the activity of tau protein, a protein involved in stabilizing microtubules. (wikipedia.org)
  • The pathophysiology of adult MG is a reduced number of acetylcholine receptors (AChR) at the postsynaptic muscle membrane due to circulating anti-AChR antibodies[4] or, less commonly, to antibodies to muscle-specific tyrosine kinase (anti-MuSK), LRP4, and agrin. (medscape.com)
  • In other patients with MG, autoantibodies target muscle-specific kinase ( MuSK ) or low-density lipoprotein receptor-related protein 4. (medscape.com)
  • PAI-1 promoted the migration of microglial cells in culture via the low-density lipoprotein receptor-related protein (LRP) 1/Janus kinase (JAK)/signal transducer and activator of transcription (STAT)1 axis. (biomedcentral.com)
  • genes are found in the receptor tyrosine kinase-RAS (RTK-RAS) signaling pathway and p53 signaling pathway, respectively. (sanger.ac.uk)
  • This adipokine plays a role as a scaffold of newly formed collagen in myocardial remodelling after ischaemic injury and also stimulates angiogenesis by promoting cross-talk between AMP-activated protein kinase and Akt signalling in endothelial cells. (biovendor.com)
  • LRP2 (also designated as megalin or gp330) is one of the superfamily of low-density-lipoprotein receptors (LDLRs) [ 7 , 8 ]. (biomedcentral.com)
  • The LRP2 gene provides instructions for making a protein called megalin, which functions as a receptor. (medlineplus.gov)
  • These mutations are believed to result in the absence of functional megalin protein. (medlineplus.gov)
  • The features of Donnai-Barrow syndrome are probably caused by the inability of megalin to help absorb these ligands, disruption of biochemical signaling pathways, or other effects of the nonfunctional megalin protein. (medlineplus.gov)
  • Christensen EI, Birn H. Megalin and cubilin: multifunctional endocytic receptors. (medlineplus.gov)
  • Here we examine expression patterns of MT-I/II and its putative receptor megalin in rat retina. (edu.au)
  • Based on previous studies, an international team led by Drs. Jennifer Rauch and Kenneth Kosik from the University of California, Santa Barbara suspected that low-density lipoprotein receptors (LDLRs) might play a role in bringing tau into cells. (nih.gov)
  • Canonical Wnt signaling is initiated by the binding of Wnt proteins to their receptors, low-density lipoprotein-related protein 5 and 6 (LRP5/6) and frizzled proteins, leading to phosphatidylinositol (4,5)bisphosphate (PtdIns(4,5)P2) production, signalosome formation, and LRP phosphorylation. (harvard.edu)
  • LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. (nature.com)
  • Microbial infection) In case of HIV-1 infection, may function as a receptor for extracellular Tat in neurons, mediating its internalization in uninfected cells. (cusabio.com)
  • Using six recombinant proteins (F2-F7) for LRP2 and one for CD69, we detected autoAbs to LRP2 in sera of patients with rheumatoid arthritis (RA), systemic lupus erythematosus, Behçet's disease, systemic sclerosis, and osteoarthritis and then mapped autoepitopes by Western blotting. (biomedcentral.com)
  • Interestingly, the amino acid sequence of this main epitope (EKNLYWI) is highly homologous to a part (EKRLYWI) of low-density-lipoprotein-receptor-related protein 2 (LRP2). (biomedcentral.com)
  • Therefore, the generation of the anti-CD69 autoAbs may be related to that of the anti-LRP2 autoAbs. (biomedcentral.com)
  • Certain LRP2 gene polymorphisms have also been associated with increased levels of low-density lipoproteins (LDLs) and cholesterol in the blood. (medlineplus.gov)
  • Major involvement of low-density lipoprotein receptor-related protein 1 in the clearance of plasma free amyloid beta-peptide by the liver. (harvard.edu)
  • The Amyloid Precursor Protein (APP) and its homologues are transmembrane proteins required for various aspects of neuronal development and activity, whose molecular function is unknown. (elifesciences.org)
  • A defining hallmark of Alzheimer's disease is the accumulation of the amyloid-beta protein, otherwise known as "senile plaques," in the brain's cortex and hippocampus, where memory consolidation occurs. (sciencedaily.com)
  • Researchers have identified a novel protein which, when over-expressed, leads to a dramatic increase in the generation of the amyloid-beta protein. (sciencedaily.com)
  • The neurotoxic protein Aβ is derived when the amyloid precursor protein (APP) is "cut" by two enzymes, β-secretase (or BACE) and γ-secretase (or Presenilin complex. (sciencedaily.com)
  • Inhibiting the RANBP9 protein may offer an alternative approach to therapy, by preventing contact between APP and the enzyme that makes the cut essential to produce amyloid plaques. (sciencedaily.com)
  • In this study, we intraperitoneally injected amyloid precursor protein (APP)/presenilin‑1 (PS1) transgenic mice with rapamycin, a known activator of autophagy that inhibits mTOR. (spandidos-publications.com)
  • Alzheimer's disease (AD) is a progressive, irreversible neurodegenerative disease and is characterized by neuronal loss, neurofibrillary tangles (NFTs) of hyperphosphorylated Tau and amyloid β-peptide (Aβ) protein accumulation ( 1 , 2 ). (spandidos-publications.com)
  • Using gene profiling, we discovered that UFPs may induce vascular endothelial cells to express genes related to clotting. (nih.gov)
  • LDL receptor-related protein 1: unique tissue-specific functions revealed by selective gene knockout studies. (harvard.edu)
  • Real-time PCR on EDTA blood targeting the gene for the major outer membrane protein lip L32 of human pathogenic Leptospira spp. (cdc.gov)
  • Low-density lipoprotein receptor-related protein 8 gene polymorphisms and dementia. (cdc.gov)
  • Mutations in the LDL receptor gene cause familial hypercholesterolemia. (embl.de)
  • A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait. (nature.com)
  • Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. (nature.com)
  • A missense mutation A214T in the low-density lipoprotein receptor related protein 5 gene. (cdc.gov)
  • Adiponectin, also referred to as Acrp30, AdipoQ and GBP-28, is a recently discovered 244 aminoacid protein, the product of the apM1 gene, which is physiologically active and specifically and highly expressed in adipose cells. (biovendor.com)
  • However the DC activation induced by all treatments was completely inhibited when these cells were pretreated with a neutralizing antiboby directed against the HSP90/70 and CRT common receptor, CD91. (hal.science)
  • Another LDL family receptor, VLDLR, also interacts with reelin, and together these two receptors influence brain development and function. (wikipedia.org)
  • We discovered that this protein interacts with three components involved in Aβ generation - LRP, APP and BACE1 - and appears to 'scaffold' them into a structure. (sciencedaily.com)
  • This protein associates with the NPXY motifs on the intracellular tails of ApoER2 and VLDLR. (wikipedia.org)
  • HFD-fed DIO mice exhibited decreased ApoER2 and VLDLR expression and increased RELN protein in the hypothalamus. (elsevierpure.com)
  • To gain insight into how Reelin signaling controls individual migrating neurons, we generated monoclonal antibodies against ApoER2 and VLDLR and examined the localization of Reelin receptors in the developing mouse cerebral cortex. (elsevierpure.com)
  • The unique topology precisely regulates apoE tertiary structure to permit only one possible conformational adaptation upon binding and provides a double security in preventing lipid-free and partially-lipidated apoE from premature binding to apoE receptors during receptor biogenesis. (nih.gov)
  • The most common subtype of autoantibody-mediated MG, comprising approximately 85% of patients , is characterised by autoantibodies against the nicotinic acetylcholine receptor ( AChR ). (medscape.com)
  • We previously reported that autoantibodies (autoAbs) to the main epitope on CD69 reacted to its homologous amino acid sequence in low-density-lipoprotein-receptor-related protein 2 (LPR2), a multiligand receptor for protein reabsorption. (biomedcentral.com)
  • In addition, as low‑density lipoprotein receptor‑related protein 6 (LRP6) is a receptor of DKK‑1 and DKK‑2 and their interaction on the cell surface inhibits Wnt/β‑catenin signaling, it was examined whether the exogenous DKK‑3 protein affects LRP6‑mediated Wnt/β‑catenin signaling. (spandidos-publications.com)
  • Background: Recent reports indicate the potential role of the stimulated by retinoic acid 6 (STRA6) protein in developing insulin resistance. (mdpi.com)
  • Adiponectin concentrations correlate negatively with glucose, insulin, triglyceride concentrations, liver fat content and body mass index and positively with high-density lipoprotein-cholesterol levels, hepatic insulin sensitivity and insulin-stimulated glucose disposal. (biovendor.com)
  • ApoER2 plays a critical role as a receptor in the reelin signalling pathway, which is important for brain development and postnatal function of the brain. (wikipedia.org)
  • GSK3β is also a pivotal regulator of the Wnt/β-catenin signalling pathway, which is closely related to the pathogenesis of AD ( 12 , 13 ). (spandidos-publications.com)
  • Cysteine-rich repeat in the low-density lipoprotein (LDL) receptor that plays a central role in mammalian cholesterol metabolism. (embl.de)
  • Certain bacteria and plants produce proteins that are able to enter and kill mammalian cells. (rupress.org)
  • Through binding of ApoER2 in the hippocampus, it plays a role in the NMDA receptor activation that is required for long-term potentiation, a mechanism by which two neurons gain a stronger, longer-lasting transmission due to simultaneous firing. (wikipedia.org)
  • Abnormal accumulations of a protein called tau can collect inside neurons, forming tangled threads and eventually causing cell death. (nih.gov)
  • A protein called tau plays an important role in maintaining the structure of normal neurons in the brain. (nih.gov)
  • These receptors sit on the outside of neurons, helping the cells to bring in cholesterol and other vital molecules. (nih.gov)
  • While scientific evidence supports the benefits of lowering low-density lipoprotein cholesterol (LDL-C) to help prevent heart disease, previous studies of cholesterol-lowering drugs have suggested a strong association between low levels of LDL-C and cancer risk. (sciencedaily.com)
  • These findings did not change when controlling for high-density lipoprotein (HDL) cholesterol levels. (sciencedaily.com)
  • All LDL receptor family proteins contain a cytoplasmic tail with at least one NPXY motif. (wikipedia.org)
  • ApoER2 is distinct from most other members of the LDL family of receptors due to a unique insert on its cytoplasmic tail. (wikipedia.org)
  • The fifth domain is the cytoplasmic tail that directs the receptor to clathrin-coated pits. (embl.de)
  • Wnt signaling serves an important role in disease development processes in adults ( 4 ), triggering at least two, perhaps three, pathways that employ Wnt receptors of the frizzled seven transmembrane classes. (spandidos-publications.com)
  • A recombinant protein of human full‑length DKK‑3 was used to investigate the exogenous effects of the protein in vitro in KPK1 human renal cell carcinoma cells. (spandidos-publications.com)
  • We noted up-regulation of genes related to coagulation [tissue factor ( F3 ) and coagulation factor II receptor-like 2 ( F2RL2 )] and differential regulation of genes related to F3 signaling ( FOS, JUN, and NFKBIA ). (nih.gov)
  • Down the road, some of the genes identified in the study may also prove useful in schizophrenia screening, researchers noted, though they conceded that more research is needed to see how findings from the current study relate to other schizophrenia cases. (genomeweb.com)
  • genes, which are involved in the Wingless-related integration site (Wnt) signaling pathway. (sanger.ac.uk)
  • ApoER2 is a cell surface receptor that is part of the low-density lipoprotein receptor family. (wikipedia.org)
  • A cancer cell viability assay confirmed the anti‑proliferative effects of exogenous DKK‑3 protein, which was consistent with a suppressed Wnt/β‑catenin signaling cascade. (spandidos-publications.com)
  • In cerebrospinal fluid, cell counts and protein concentration were within reference limits, but intrathecal IgG production was evident. (cdc.gov)
  • PAI-1 plays a dual role in the regulation of cell migration through differential interactions with its binding partners such as uPA, tPA, vitronectin, and low-density lipoprotein receptor-related protein (LRP)1. (biomedcentral.com)
  • The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself. (cusabio.com)
  • RANBP9 is one of the proteins we identified that interacted with this LRP segment, but one that had never before been associated with disease-related neuronal changes," said Kang. (sciencedaily.com)
  • This insert allows for protein interactions that are unable to occur with other LDL receptors. (wikipedia.org)
  • Secretion entails transport of the proteins from the ER, via the Golgi stack and the TGN, to secretory vesicles that ultimately fuse with the plasma membrane to complete protein export. (rupress.org)
  • Unfolding of the RAP-D3 helical bundle facilitates dissociation of RAP-receptor complexes. (harvard.edu)
  • Together, these complexes make up approximately 0.01% of total serum protein. (biovendor.com)
  • 7. Cathepsin D protein levels in colorectal tumors: divergent expression patterns suggest complex regulation and function. (nih.gov)
  • As such, a small molecule drug that can reduce the RANBP9 protein levels could offer an effective treatment for Alzheimer's disease. (sciencedaily.com)
  • The levels of PAI-1 mRNA and protein expression were increased by lipopolysaccharide and interferon-γ stimulation in both microglia and astrocytes. (biomedcentral.com)
  • Paradoxically, adipose tissue-expressed adiponectin levels are inversely related to the degree of adiposity. (biovendor.com)
  • Low-density lipoprotein receptor-related protein-1 (LRP-1), but not p-glycoprotein, may be involved in α-Syn efflux and lipopolysaccharide (LPS)-induced inflammation could increase α-Syn uptake by the brain by disrupting the BBB. (nih.gov)
  • Low-density lipoprotein receptor-related protein catabolizes Factor VIII and Factor VIIIa using different modes of interaction. (nih.gov)
  • Microbial infection) Acts as a receptor for hepatitis C virus in hepatocytes, but not through a direct interaction with viral proteins. (cusabio.com)
  • suggesting the intriguing possibility that APP may itself be a receptor for Wnt family member. (elifesciences.org)
  • 17. The zinc finger protein OZF (ZNF146) is overexpressed in colorectal cancer. (nih.gov)
  • By controlling access to the brain, the blood-brain barrier (BBB) restricts the entry of proteins and potential drugs to cerebral tissues. (aspetjournals.org)
  • LDL-Receptor Related Protein-Associated Protein" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (harvard.edu)
  • As an ancient and highly conserved protein, APP and its homologs are found across animal species in both vertebrates and invertebrates ( Shariati and De Strooper, 2013 ). (elifesciences.org)
  • Alpha-synuclein (α-Syn), a small protein with multiple physiological and pathological functions, is one of the dominant proteins found in Lewy Bodies, a pathological hallmark of Lewy body disorders, including Parkinson's disease (PD). (nih.gov)
  • The role of the multi-domain protein, RANBP9, suggests a possible new therapeutic target for Alzheimer's disease," said David E. Kang, PhD, assistant professor of neurosciences at UC San Diego and director of this study. (sciencedaily.com)
  • In LDL receptors, the class A domains form the binding site for LDL and calcium. (embl.de)
  • Numerous familial hypercholestorolemia mutations of the LDL receptor alter the calcium coordinating residue of LDL-A domains or other crucial scaffolding residues. (embl.de)