Smooth Muscle LDL Receptor-Related Protein-1 Deletion Induces Aortic Insufficiency and Promotes Vascular Cardiomyopathy in Mice. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Hep I stimulates association of LRP with the Gαi2 subunit, and association is blocked by RAP and by peptides corresponding to the COOH terminus of Gαi2. (A) BAE cells were grown to near confluence and serum deprived overnight. Cells were then treated with 1 μM hep I for 0, 5, 10, 15, or 30 min and lysed. Cell lysates were immunoprecipitated with monoclonal anti-LRP antibody (8G1), separated by SDS-PAGE, and immunoblotted with mouse anti-Gαi2 antibodies. A representative immunoblot for LRP-associated Gαi2 is shown. Bands were analyzed using One-Dscan software (Scanalytics), and the fold change in LRP-Gαi2 association as compared with untreated conditions was determined. Equal loading of sample protein was assessed by protein staining with Ponceau S. *, P , 0.05; **, P , 0.01 (n = 3-5). (B) BAE cells were grown as in A, treated for 10 min with either DMEM, 100 nM hep I, 78 nM TSP, or 100 nM modified hep I and assayed for LRP-Gαi2 association as described in A. A representative immunoblot ...
Buy LRP1 elisa kit, Sheep Low-Density Lipoprotein Receptor-Related Protein 1 ELISA Kit-AAH72015.1 (MBS021833) product datasheet at MyBioSource, ELISA Kits
Ling, TY et al. (2004) Identification and characterization of the acidic pH binding sites for growth regulatory ligands of low density lipoprotein receptor-related protein-1. J. Biol. Chem. 279 38736-48 PubMed GONUTS page ...
PubMed Central Canada (PMC Canada) provides free access to a stable and permanent online digital archive of full-text, peer-reviewed health and life sciences research publications. It builds on PubMed Central (PMC), the U.S. National Institutes of Health (NIH) free digital archive of biomedical and life sciences journal literature and is a member of the broader PMC International (PMCI) network of e-repositories.
LDL receptor-related protein (LRP) is a multifunctional cell surface receptor that is expressed in many cell types. It is able to bind numerous structurally unrelated ligands. This thesis describes four novel functions of LRP in different cell types. β2-integrins are heterodimeric proteins present at the cell surface of leukocytes. They are ... read more involved in various processes, like leukocyte adhesion to the vascular wall. We reported that LRP directly bound to the α-subunit of β2-integrins. Upon activation, β2-integrins form clusters in rafts of monocytes to increase the avidity for its ligands. LRP was co-immunoprecipitated with β2-integrins in the raft fraction of both naïve and stimulated monocytes. In addition, LRP colocalized with β2-integrins in the clusters. Downregulation of LRP disrupted the β2-integrin clusters, which resulted in a decreased adhesion of monocytes to activated endothelium. These data indicate that LRP is required for optimal β2-integrin function. These ...
The alpha 2-macroglobulin (alpha 2M) receptor/low-density lipoprotein receptor-related protein (LRP) is important for the clearance of proteases, protease-inhibitor complexes, and various ligands associated with lipid metabolism. While the regulation of receptor function is poorly understood, the addition of high concentrations of the 39-kD receptor-associated protein (RAP) to cells inhibits the binding and/or uptake of many of these ligands. Previously, we (Kounnas, M.Z., R.E. Morris, M.R. Thompson, D.J. FitzGerald, D.K. Strickland, and C.B. Saelinger. 1992. J. Biol. Chem. 267:12420-12423) [corrected] showed that Pseudomonas exotoxin (PE) could bind immobilized LRP. Also, the addition of RAP blocked toxin-mediated cell killing. These findings suggested that PE might use LRP to gain entry into toxin-sensitive cells. Here we report on a strategy to select PE-resistant lines of Chinese hamster ovary cells that express altered amounts of LRP. An important part of this strategy is to screen ...
Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value | 1 × 10(-5)) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p | 1 × 10(-5)). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10(-10), odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535
3.3.co;2-i. PMID 11425005. Aldahmesh MA, Khan AO, Alkuraya H, Adly N, Anazi S, Al-Saleh AA, Mohamed JY, Hijazi H, Prabakaran S, Tacke M, Al-Khrashi A, Hashem M, Reinheckel T, Assiri A, Alkuraya FS. "Mutations in LRPAP1 Are Associated with Severe Myopia in Humans". Am J Hum Genet. 93: 313-20. doi:10.1016/j.ajhg.2013.06.002. PMC 3738831 . PMID 23830514. Aldahmesh MA, Khan AO, Alkuraya H, Adly N, Anazi S, Al-Saleh AA, Mohamed JY, Hijazi H, Prabakaran S, Tacke M, Al-Khrashi A, Hashem M, Reinheckel T, Assiri A, Alkuraya FS (2013). "Mutations in LRPAP1 are associated with severe myopia in humans". American Journal of Human Genetics. 93 (2): 313-20. doi:10.1016/j.ajhg.2013.06.002. PMC 3738831 . PMID 23830514. Willnow TE, Armstrong SA, Hammer RE, Herz J (1995). "Functional expression of low density lipoprotein receptor-related protein is controlled by receptor-associated protein in vivo". Proceedings of the National Academy of Sciences of the United States of America. 92 (10): 4537-41. ...
LRP5 - LRP5 (GFP-tagged) - Human low density lipoprotein receptor-related protein 5 (LRP5) available for purchase from OriGene - Your Gene Company.
Prolow-density lipoprotein receptor-related protein 1 precursor (LRP)(Alpha-2-macroglobulin receptor) (A2MR) (Apolipoprotein E receptor)(APOER) (CD91 antigen) [Contains: Low-density lipoprotein receptor-related protein 1 85 kDa subunit (LRP-85); Low-density lipoproteinreceptor-related protein 1 515 kDa subunit (LRP-515); Low-densitylipoprotein receptor-related protein 1 intracellular domain (LRPICD ...
Second immunoglobulin (Ig) domain of nectin-3 (also known as poliovirus receptor related protein 3), nectin-4 (poliovirus receptor related protein 4) and similar proteins. Ig2_Nectin-3-4_like: domain similar to the second immunoglobulin (Ig) domain of nectin-3 (also known as poliovirus receptor related protein 3) and nectin-4 (poliovirus receptor related protein 4). Nectin-3 and nectin-4 belong to the nectin family comprised of four transmembrane glycoproteins (nectins-1 through 4). Nectins are synaptic cell adhesion molecules (CAMs) which facilitate adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. Nectin-2 and nectin-3 localize at Sertoli-spermatid junctions where they form heterophilic trans-interactions between the cells that are essential for the formation and maintenance of the junctions and for spermatid development. Nectin-3 has also been shown to form a ...
Ulery PG, Beers J, Mikhailenko I, Tanzi RE, Rebeck GW, Hyman BT, Strickland DK. Modulation of beta-amyloid precursor protein processing by the low density lipoprotein receptor-related protein (LRP). Evidence that LRP contributes to the pathogenesis of Alzheimers disease ...
pep:known chromosome:VEGA66:19:3584828:3686556:-1 gene:OTTMUSG00000042195 transcript:OTTMUST00000110769 gene_biotype:protein_coding transcript_biotype:protein_coding gene_symbol:Lrp5 description:low density lipoprotein receptor-related protein 5 ...
Reagents, Tools and Custom Services for molecular biology, specializing in the fields of Nano-Antibody development (nAb), Cellular Reprogramming (iPSC), Genome Editing, Fluorescent Proteins, RNAi, Viral Packaging and Protein expression.
Reagents, Tools and Custom Services for molecular biology, specializing in the fields of Nano-Antibody development (nAb), Cellular Reprogramming (iPSC), Genome Editing, Fluorescent Proteins, RNAi, Viral Packaging and Protein expression.
Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene, low density lipoprotein-related protein 2 (LRP2) or megalin, is a multi-ligand endocytic receptor that is expressed in many different tissues but primarily in absorptive epithilial tissues such as the kidney. This glycoprotein has a large amino-terminal extracellular domain, a single transmembrane domain, and a short carboxy-terminal cytoplasmic tail. The extracellular ligand-binding-domains bind diverse macromolecules including albumin, apolipoproteins B and E, and lipoprotein lipase. The LRP2 protein is critical for the reuptake of numerous ligands, including lipoproteins, sterols, vitamin-binding proteins, and hormones. This protein also has a role in cell-signaling; extracellular ligands include parathyroid horomones and the morphogen sonic hedgehog while cytosolic ligands include MAP kinase scaffold proteins and JNK interacting proteins. Recycling of this membrane receptor ...
The cell surface receptor, low-density lipoprotein receptor-related protein 5 (LRP5) is a key regulator of bone mass and strength. LRP5 loss-of-function mutatio...
Maletínská, Lenka et al "Human Glioblastoma Cell Lines: Levels of Low-Density Lipoprotein Receptor and Low-Density Lipoprotein Receptor-related Protein." Cancer Research 60.8 (2000): 2300-2303. Web. 09 Aug. 2020. ...
Pietrzik CU, Yoon IS, Jaeger S, Busse T, Weggen S, Koo EH. FE65 constitutes the functional link between the low-density lipoprotein receptor-related protein and the amyloid precursor protein ...
The integration of lipoprotein-related or apolipoprotein-targeted nanoparticles as pharmaceutical carriers opens new therapeutic and diagnostic avenues in nanom
This gene encodes a high-affinity dickkopf homolog 1 (DKK1) transmembrane receptor that functionally cooperates with DKK1 to block wingless (WNT)/beta-catenin signaling. The encoded protein is a component of a membrane complex that modulates canonical WNT signaling through lipoprotein receptor-related protein 6 (LRP6). It contains extracellular kringle, WSC, and CUB domains. Alternatively spliced transcript variants encoding distinct isoforms have been observed for this gene. [provided by RefSeq, Jul 2008 ...
Complete information for LRP6 gene (Protein Coding), LDL Receptor Related Protein 6, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Complete information for LRPAP1 gene (Protein Coding), LDL Receptor Related Protein Associated Protein 1, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Gelatinase B/matrix metalloproteinase-9 (MMP-9), a key regulator and effector of immunity, contains a C-terminal hemopexin domain preceded by a unique linker sequence of ?64 amino acid residues. This linker sequence is demonstrated to be an extensively O-glycosylated (OG) domain with a compact three-dimensional structure. The OG and hemopexin domains have no influence on the cleavage efficiency of MMP-9 substrates. In contrast, the hemopexin domain contains a binding site for the cargo receptor low density lipoprotein receptor-related protein-1 (LRP-1). Furthermore, megalin/LRP-2 is identified as a new functional receptor for the hemopexin domain of MMP-9, able to mediate the endocytosis and catabolism of the enzyme. The OG domain is required to correctly orient the hemopexin domain for inhibition by TIMP-1 and internalization by LRP-1 and megalin. Therefore, the OG and hemopexin domains down-regulate the bioavailability of active MMP-9 and the interactions with the cargo receptors are proposed ...
Internalization of the urokinase-type plasminogen activator (uPA) requires two receptors, the uPA receptor (uPAR) and the low density lipoprotein receptor-related protein (LRP)/alpha2-macroglobulin (alpha2M) receptor. Here, we address whether protein kinases are involved in the internalization of uPA by human melanoma cells. Initially, we found that the internalization of uPA was significantly inhibited by the serine/threonine protein kinase inhibitors staurosporine, K-252a and H-89, but not by the tyrosine kinase inhibitors, genistein and lavendustin A. Internalization of uPA was also inhibited by a pseudosubstrate peptide for cAMP-dependent protein kinase (PKA), but not by a pseudosubstrate peptide for protein kinase C. We confirmed a requirement for PKA-activity and implicated a specific isoform by using an antisense oligonucleotide against the regulatory subunit RI alpha of PKA which suppresses PKA-I activity. Exposure of cells to this oligonucleotide led to a specific, dose-dependent ...
Midkine (MK or MDK) also known as neurite growth-promoting factor 2 (NEGF2) is a protein that in humans is encoded by the MDK gene. Midkine is a basic heparin-binding growth factor of low molecular weight, and forms a family with pleiotrophin (NEGF1, 46% homologous with MK). It is a nonglycosylated protein, composed of two domains held by disulfide bridges. It is a developmentally important retinoic acid-responsive gene product strongly induced during mid-gestation, hence the name midkine. Restricted mainly to certain tissues in the normal adult, it is strongly induced during oncogenesis, inflammation and tissue repair. MK is pleiotropic, capable of exerting activities such as cell proliferation, cell migration, angiogenesis and fibrinolysis. A molecular complex containing receptor-type tyrosine phosphatase zeta (PTPζ), low density lipoprotein receptor-related protein (LRP1), anaplastic leukemia kinase (ALK) and syndecans is considered to be its receptor. MK appears to enhance the angiogenic ...
TY - JOUR. T1 - FZD7 has a critical role in cell proliferation in triple negative breast cancer. AU - Yang, L.. AU - Wu, X.. AU - Wang, Y.. AU - Zhang, K.. AU - Wu, J.. AU - Yuan, Y. C.. AU - Deng, X.. AU - Chen, L.. AU - Kim, C. C.H.. AU - Lau, S.. AU - Somlo, G.. AU - Yen, Y.. PY - 2011/10/27. Y1 - 2011/10/27. N2 - Breast cancer is genetically and clinically heterogeneous. Triple negative breast cancer (TNBC) is a subtype of breast cancer that is usually associated with poor outcome and lack of benefit from targeted therapy. We used microarray analysis to perform a pathway analysis of TNBC compared with non-triple negative breast cancer (non-TNBC). Overexpression of several Wnt pathway genes, such as frizzled homolog 7 (FZD7), low density lipoprotein receptor-related protein 6 and transcription factor 7 (TCF7) was observed in TNBC, and we directed our focus to the Wnt pathway receptor, FZD7. To validate the function of FZD7, FZD7shRNA was used to knock down FZD7 expression. Notably, reduced ...
LRPAP1 is involved with trafficking of certain members of the LDL receptor family including LRP1 and LRP2.The alpha-2-macroglobulin receptor complex, as purified by affinity chromatography, contains 3 polypeptides: a 515-kD heavy chain, an 85-kD light chain, and a 39-kD associated protein.The deduced amino acid sequence contains a putative signal sequence that precedes the 323-residue mature protein. The sequence showed 73% identity with a rat protein reported to be a pathogenic domain of the Heymann nephritis antigen gp330 and 77% identity to a 44-kD mouse heparin-binding protein termed HBP-44. There are also similarities between MRAP and apolipoprotein E. Studies indicated that the molecule is present on the cell surface, forming a complex with the heavy and light chains of the alpha-2-macroglobulin receptor.
The low-density lipoprotein (LDL) receptor plays a central role in mammalian cholesterol metabolism, clearing lipoproteins which bear apolipoproteins E and B-100 from plasma. Mutations in this molecule are associated with familial hypercholesterolemia, a condition which leads to an elevated plasma cholesterol concentration and accelerated atherosclerosis. The N-terminal segment of the LDL receptor contains a heptad of cysteine-rich repeats that bind the lipoproteins. Similar repeats are present 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. The first repeat of the human LDL receptor has been expressed in Escherichia coli as a glutathione S-transferase fusion protein, and the cleaved and purified receptor module has been shown to fold to a single, fully oxidized form that is recognized by the monoclonal antibody ...
The low-density lipoprotein (LDL) receptor plays a central role in mammalian cholesterol metabolism, clearing lipoproteins which bear apolipoproteins E and B-100 from plasma. Mutations in this molecule are associated with familial hypercholesterolemia, a condition which leads to an elevated plasma cholesterol concentration and accelerated atherosclerosis. The N-terminal segment of the LDL receptor contains a heptad of cysteine-rich repeats that bind the lipoproteins. Similar repeats are present 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. The first repeat of the human LDL receptor has been expressed in Escherichia coli as a glutathione S-transferase fusion protein, and the cleaved and purified receptor module has been shown to fold to a single, fully oxidized form that is recognized by the monoclonal antibody ...
LRP1 is known to be a receptor for signal transmission and endocytosis. We formerly reported that LRP1 regulates WNT/β-catenin and protein kinase C signaling in chondrocytes and represses the hypertrophy of chondrocytes during endochondral ossification, and that LRP1 is co-localized with a ligand, CCN2, which conducts endochondral ossification, on chondrocytes. However, the role of LRP1 in endocytotic transport of CCN2 in chondrocytes is not yet understood. In the present study, we investigated the interaction between LRP1 and CCN2 during endocytotic trafficking.. RNAi-mediated knockdown of LRP1 in chondrocytic HCS-2/8 cells showed that the amount of exogenous CCN2 binding/incorporation was decreased in the LRP1 down-regulated cells. Importantly, we observed that CCN2 internalization in chondrocytes was dependent on clathrin and internalizated CCN2 was co-localized with an early or recycling endosome marker. Transcytosis of CCN2 through HCS-2/8 cells was confirmed by performing experiments with ...
The low-density lipoprotein receptor-related protein 4 (LRP4) is essential in muscle fibers for the establishment of the neuromuscular junction. Here, we show that LRP4 is also expressed by embryonic cortical and hippocampal neurons, and that downregulation of LRP4 in these neurons causes a reduction in density of synapses and number of primary dendrites. Accordingly, overexpression of LRP4 in cultured neurons had the opposite effect inducing more but shorter primary dendrites with an increased number of spines. Transsynaptic tracing mediated by rabies virus revealed a reduced number of neurons presynaptic to the cortical neurons in which LRP4 was knocked down. Moreover, neuron-specific knockdown of LRP4 by in utero electroporation of LRP4 miRNA in vivo also resulted in neurons with fewer primary dendrites and a lower density of spines in the developing cortex and hippocampus. Collectively, our results demonstrate an essential and novel role of neuronal LRP4 in dendritic development and ...
Context: Mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene cause rare syndromes characterized by altered bone mineral density (BMD). More common LRP5 variants may affect osteoporosis risk in the general population.. Objective: To generate large-scale evidence on whether 2 common variants ofLRP5 (Val667Met, Ala1330Val) and 1 variant of LRP6 (Ile1062Val) are associated with BMD and fracture risk.. Design and Setting: Prospective, multicenter, collaborative study of individual-level data on 37 534 individuals from 18 participating teams in Europe and North America. Data were collected between September 2004 and January 2007; analysis of the collected data was performed between February and May 2007. Bone mineral density was assessed by dual-energy x-ray absorptiometry. Fractures were identified via questionnaire, medical records, or radiographic documentation; incident fracture data were available for some cohorts, ascertained via routine surveillance methods, ...
0128]The LRP-1 or LRP-2 molecules are also useful as pharmacodynamic markers. As used herein, a "pharmacodynamic marker" is an objective biochemical marker which correlates specifically with drug effects. The presence or quantity of a pharmacodynamic marker is not related to the disease state or disorder for which the drug is being administered; therefore, the presence or quantity of the marker is indicative of the presence or activity of the drug in a subject. For example, a pharmacodynamic marker can be indicative of the concentration of the drug in a biological tissue, in that the marker is either expressed or transcribed or not expressed or transcribed in that tissue in relationship to the level of the drug. In this fashion, the distribution or uptake of the drug can be monitored by the pharmacodynamic marker. Similarly, the presence or quantity of the pharmacodynamic marker can be related to the presence or quantity of the metabolic product of a drug, such that the presence or quantity of ...
Seven transmembrane receptors are divided into classic and atypical families. The former represents GPCRs, and the latter includes Frizzled (FZD). FZD is the receptor for Wnt, a family of highly conserved secreted glycoproteins (Cadigan and Nusse, 1997; Wodarz and Nusse, 1998). Until recently, it has been believed that these two receptor systems use distinct downstream signaling pathways; however, some recent studies have shown that two pathways might interact each other by sharing intermediate signaling components such as G proteins, GPCR kinase (GRKs), β-arrestins, Axins (axis inhibitor I), or scaffolding proteins such as Dvl family proteins (Force et al., 2007).. The canonical Wnt pathway is activated when Wnt proteins bind to FZD and low-density lipoprotein receptor-related protein 5/6 (LRP5/6) located on the plasma membrane, causing the receptors to activate Dvl family proteins, which are cytoplasmic signaling proteins (Moon, 2005). These series of events ultimately alter the level of ...
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Osteoporosis-pseudoglioma syndrome (OPPG; MIM 259770) is an autosomal recessive disorder characterized by early onset vision loss and osteoporosis. Reported eye findings include pseudoglioma, phthisis bulbi, microphthalmia, cataracts, absent anterior eye chambers and various vitreoretinal abnormalities. Individuals lacking vitreoretinal abnormalities may not have osteoporosis-pseudoglioma syndrome. Most patients are blind by 15 years of age. Bone fragility and severe osteoporosis resulting in spontaneous fractures, long bone deformities, short stature, kyphoscoliosis, pseudoarthrosis and platyspondyly have been described. Most cases of OPPG are caused by loss of function mutations in the low density lipoprotein receptor-related protein-5 gene (LRP5). DNA sequencing of the LRP5 gene will define mutations in more than 70% of cases. The findings in OPPG overlap with features of exudative vitreoretinopathy 4 (MIM 601813).. Read less ...
The involvement of circulating insulin-like growth factor I (IGF-I) in the beneficial effects of physical exercise on the brain makes this abundant serum growth factor a physiologically relevant neuroprotective signal. However, the mechanisms underlying neuroprotection by serum IGF-I remain primarily unknown. Among many other neuroprotective actions, IGF-I enhances clearance of brain amyloid β (Aβ) by modulating transport/production of Aβ carriers at the blood-brain interface in the choroid plexus. We found that physical exercise increases the levels of the choroid plexus endocytic receptor megalin/low-density lipoprotein receptor-related protein-2 (LRP2), a multicargo transporter known to participate in brain uptake of Aβ carriers. By manipulating choroid plexus megalin levels through viral-directed overexpression and RNA interference, we observed that megalin mediates IGF-I-induced clearance of Aβ and is involved in IGF-I transport into the brain. Through this dual role, megalin ...
Myasthenia gravis (MG) and the Lambert-Eaton myasthenic syndrome (LEMS) are the prototypical autoimmune channelopathies of the peripheral nervous system. The predominant neuromuscular junction antigenic targets are either postsynaptic (MG; nicotinic acetylcholine receptor (AChR)) or presynaptic (LEMS; voltage-gated calcium channels (VGCCs)). Over the last 35 years the development of active immunization, passive transfer models, and use of transgenic animals has greatly enhanced our understanding of the biology of these disorders. The search for other antibodies in previously seronegative MG cases has led to the recognition of antibodies against clustered AChRs, muscle-specific kinase (MuSK) and low density lipoprotein receptor-related protein 4 (Lrp4). The pathogenic mechanisms that underlie these newer serological subclasses of MG are not yet fully understood, but are likely to be different from AChR antibody-mediated disease. While many still would consider MG an antibody-mediated disorder, it is
PubMed Central Canada (PMC Canada) provides free access to a stable and permanent online digital archive of full-text, peer-reviewed health and life sciences research publications. It builds on PubMed Central (PMC), the U.S. National Institutes of Health (NIH) free digital archive of biomedical and life sciences journal literature and is a member of the broader PMC International (PMCI) network of e-repositories.
In the vascular compartment, in response to local thrombosis, the serine protease tissue-type plasminogen activator (tPA) converts fibrin-bound plasminogen into active plasmin, leading to fibrin blood clot degradation.1 Accumulating evidence also indicate that apart from this fibrinolytic activity, tPA plays critical roles in the brain parenchyma, including the control of some cognitive processes in the healthy brain as well as neuronal survival after injuries to the central nervous system.2,3. In the brain parenchyma, tPAs substrates or interaction partners are multiple, thus extending its mode of action below the sole activation of plasminogen. Indeed, the interaction between tPA and the low-density lipoprotein receptor-related protein, the N-methyl-d-aspartate receptor (NMDAR), annexin II in glial cells, and/or neurons activates cell signaling processes that result in different outcomes depending on the physiological or pathological contexts. This complexity is for instance illustrated by ...
Cartilage degradation in osteoarthritis (OA) is now well established to be the result of elevated proteinase activities, with the key enzymes being aggrecanases and collagenases. Their activities are not readily detected in normal cartilage, but they are greatly upregulated under pathological conditions, such as rheumatoid arthritis (RA) and OA, at the levels of transcription, epigenetic modification, posttranscriptional regulation by microRNAs, activation of pro-enzymes and inhibition by endogenous inhibitors. Recently, I have discovered an additional regulatory mechanism in that many of the key matrix-degrading metalloproteinases are rapidly endocytosed and degraded by chondrocytes in healthy cartilage, and this process is mediated by the endocytic receptor, low-density lipoprotein receptor-related protein 1 (LRP1) on the cell surface. However, under inflammatory conditions, or in OA cartilage, the LRP1 is proteolytically shed from the cell surface, which impairs the endocytic pathway. This ...
The Wnt family of growth factors and components of their signalling pathways have diverse roles in development and disease. Wnt signalling influences many aspects of embryonic patterning, cell proliferation as well as the maintenance and differentiation of stem cells, and is critical in axis formation (figure 1b; reviewed in Moon et al. 2004; Kohn & Moon 2005; Clevers 2006). In the absence of the so-called canonical Wnt signalling (Wnt/β-catenin), β-catenin is rapidly sequestered in a cytoplasmic degradation complex containing axin, the adenomatous polyposis tumour suppressor protein (APC) and the serine threonine kinase GSK-3β. GSK-3 phosphorylation of β-catenin targets the latter for proteasomal degradation (figure 1b). Wnt binding to its co-receptors Frizzled and LRP5/6 (low-density lipoprotein receptor-related protein) activates a cytoplasmic phosphoprotein (Dishevelled, Dsh) which downregulates GSK-3 and inhibits the degradation of β-catenin. Stabilized β-catenin protein interacts ...
Without appropriate signaling by the Sonic hedgehog (SHH) pathway, the forebrain does not develop correctly; in humans, this leads to holoprosencephaly. Loss or reduced activity of Megalin, also known as lipoprotein receptor-related protein 2 (LRP2), produces phenotypes similar to holoprosencephaly in humans. LRP2 binds two morphogens implicated in forebrain development, BMP4 and SHH. Christ et al. set out to determine which of these binding partners was important for the effects of LRP2 in early forebrain specification. LRP2 was detected at embryonic day 7.5 (E7.5) at the apical side of the developing neural plate and became progressively restricted to the midline by E10.5. In situ hybridization at E8.0 for Shh and Six3, which mutually regulate each others expression, showed that Six3 was reduced in the prospective forebrain area of lrp2-knockout mice. Although Shh was present in the prechordal plate that specifies the rostral diencephalon ventral midline (RDVM), which are the cells that will ...
The canonical Wnt/beta-catenin pathway plays a key role in the regulation of bone remodeling in mice and humans. Two transmembrane proteins that are involved in decreasing the activity of this pathway by binding to extracellular antagonists, such as Dickkopf 1 (Dkk1), are the low-density lipoprotein receptor related protein 5 (Lrp5) and Kremen 2 (Krm2). Lrp 5 deficiency (Lrp5(-/-)) as well as osteoblast-specific overexpression of Krm2 in mice (Col1a1-Krm2) result in severe osteoporosis occurring at young age. In this study, we analyzed the influence of Lrp5 deficiency and osteoblast-specific overexpression of Krm2 on fracture healing in mice using flexible and semi-rigid fracture fixation. We demonstrated that fracture healing was highly impaired in both mouse genotypes, but that impairment was more severe in Col1a1-Krm2 than in Lrp5(-/-) mice and particularly evident in mice in which the more flexible fixation was used. Bone formation was more reduced in Col1a1-Krm2 than in Lrp5(-/-) mice, ...
Neurotoxic amyloid β peptide (Aβ) accumulates in the brains of individuals with Alzheimer disease (AD). The APOE4 allele is a major risk factor for sporadic AD and has been associated with increased brain parenchymal and vascular amyloid burden. How apoE isoforms influence Aβ accumulation in the brain has, however, remained unclear. Here, we have shown that apoE disrupts Aβ clearance across the mouse blood-brain barrier (BBB) in an isoform-specific manner (specifically, apoE4 had a greater disruptive effect than either apoE3 or apoE2). Aβ binding to apoE4 redirected the rapid clearance of free Aβ40/42 from the LDL receptor-related protein 1 (LRP1) to the VLDL receptor (VLDLR), which internalized apoE4 and Aβ-apoE4 complexes at the BBB more slowly than LRP1. In contrast, apoE2 and apoE3 as well as Aβ-apoE2 and Aβ-apoE3 complexes were cleared at the BBB via both VLDLR and LRP1 at a substantially faster rate than Aβ-apoE4 complexes. Astrocyte-secreted lipo-apoE2, lipo-apoE3, and ...
Gong Y, Slee RB, Fukai N, Rawadi G, Roman-Roman S, Reginato AM, Wang H, Cundy T, Glorieux FH, Lev D, Zacharin M, Oexle K, Marcelino J, Suwairi W, Heeger S, Sabatakos G, Apte S, Adkins WN, Allgrove J, Arslan-Kirchner M, Batch JA, Beighton P, Black GC, Boles RG, Boon LM, Borrone C, Brunner HG, Carle GF, Dallapiccola B, De Paepe A, Floege B, Halfhide ML, Hall B, Hennekam RC, Hirose T, Jans A, Jüppner H, Kim CA, Keppler-Noreuil K, Kohlschuetter A, LaCombe D, Lambert M, Lemyre E, Letteboer T, Peltonen L, Ramesar RS, Romanengo M, Somer H, Steichen-Gersdorf E, Steinmann B, Sullivan B, Superti-Furga A, Swoboda W, van den Boogaard MJ, Van Hul W, Vikkula M, Votruba M, Zabel B, Garcia T, Baron R, Olsen BR, Warman ML. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell. 2001 Nov 16; 107(4):513-23. PMID: 11719191. ...
gi,74761016,sp,Q96NY8.1,PVRL4_HUMAN RecName: Full=Poliovirus receptor-related protein 4; AltName: Full=Ig superfamily receptor LNIR; AltName: Full=Nectin-4; Contains: RecName: Full=Processed poliovirus receptor-related protein 4; Flags: ...
Human Receptor Associated Protein (RAP) is a protein that interacts with the low density lipoprotein (LDL) receptor-related protein and facilitates its proper folding and localization by preventing the binding of ligands. The stable mutant form of human