CD59, an 18-20-kD complement inhibitor anchored to the membrane via glycosyl phosphatidylinositol (GPI), can induce activation of T cells and neutrophils upon cross-linking with antibody. GPI-anchored molecules cocluster in high mol wt detergent-resistant complexes containing tyrosine kinases that are implicated in the signaling pathway. Exogenous, incorporated GPI-anchored molecules are initially unable to induce activation, presumably because they are not associated with kinases. Here we demonstrate that erythrocyte-derived CD59 incorporated in a CD59-negative cell line acquires signaling capacity in a time-dependent manner. Confocal microscopy revealed an initial diffuse distribution of CD59 that became clustered within 2 h to give a pattern similar to endogenous GPI-anchored molecules. Gel filtration of detergent-solubilized cells immediately after incorporation revealed that CD59 was mainly monomeric, but after 3 h incubation all was in high mol wt complexes and had become associated with ...
A series of synthetic analogues of 1-d-(2-amino-2-deoxy-α-d-glucopyranosyl)-myo-inositol 1-(1,2-di-O-hexadecanoyl-sn-glycerol 3-phosphate), consisting of 7 variants of either the d-myo-inositol, d-GlcpN or the phospholipid components, were prepared and tested as substrates and inhibitors of GlcNAc-PI de-N-acetylase, a genetically validated drug target enzyme responsible for the second step in the glycosylphosphatidylinositol (GPI) biosynthetic pathway of Trypanosoma brucei. The d-myo-inositol in the physiological substrate was successfully replaced by cyclohexanediol and is still a substrate for T. brucei GlcNAc-PI de-N-acetylase. However, this compound became sensitive to the stereochemistry of the glycoside linkage (the β-anomer was neither substrate or inhibitor) and the structure of the lipid moiety (the hexadecyl derivatives were inhibitors). Chemistry was successfully developed to replace the phosphate with a sulphonamide, but the compound was neither a substrate or an inhibitor, ...
African sleeping sickness is a debilitating and often fatal disease caused by tsetse fly transmitted African trypanosomes. These extracellular protozoan parasites survive in the human bloodstream by virtue of a dense cell surface coat made of variant surface glycoprotein. The parasites have a repertoire of several hundred immunologically distinct variant surface glycoproteins and they evade the host immune response by antigenic variation. All variant surface glycoproteins are anchored to the plasma membrane via glycosylphosphatidylinositol membrane anchors and compounds that inhibit the assembly or transfer of these anchors could have trypanocidal potential. This article compares glycosylphosphatidylinositol biosynthesis in African trypanosomes and mammalian cells and identifies several steps that could be targets for the development of parasite-specific therapeutic agents. (C) 1999 Elsevier Science B.V. All rights reserved. ...
Our company is a supplier of ELISA kits. The price is fair. The pre-sale, in-sale and after-sale services are at your service. Provide free test service, please call us! Human glycophosphatidylinositol (GPI) enzyme-linked immunoassay (ELISA) Kit instruction manual This reagent is for research use only Purpose: This kit is used to determine the content of glycophosphatidylinositol (GPI) in human serum, plasma and related liquid samples. Experimental principle: This kit uses the double antibody sandwich method to determine the level of human glycophosphatidylinositol (GPI) in the specimen. Microporous plates were coated with purified human glycophosphatidylinositol (GPI) antibody to make solid-phase antibodies, and glycophosphatidylinositol (GPI) was added to the monoclonal antibody-coated microwells in turn, followed by HRP-labeled sugar Phosphatidylinositol (GPI) antibody binds to form an antibody-antigen-enzyme-labeled antibody complex. After thorough washing, the substrate TMB is added for ...
This gene encodes a protein that is involved in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor is a glycolipid found on many blood cells and serves to anchor proteins to the cell surface. This protein is expressed in the endoplasmic reticulum and transfers phosphoethanolamine (EtNP) to the first mannose of the GPI anchor. Two alternatively spliced variants, which encode an identical isoform, have been reported. [provided by RefSeq, Jul 2008 ...
Lenti ORF particles, PIGP (Myc-DDK tagged) - Human phosphatidylinositol glycan anchor biosynthesis, class P (PIGP), transcript variant 2 , 200 uL, |10^7 TU/mL, 200 µl.
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... , Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol.
Endotoxin stimulates leukocytes to release cytokines that initiate septic shock in humans and animals. CD14, a glycosyl-phosphatidylinositol-anchored membrane glycoprotein, is an endotoxin receptor on leukocytes, and endotoxin binding to CD14 induces cytokine production. Here we show that glycosyl-phosphatidylinositol-anchored or integral membrane CD14 mediates identical cellular responses to endotoxin, including NF-kappa B activation and protein tyrosine phosphorylation. We also show that an anti-CD14 monoclonal antibody that does not block endotoxin binding to CD14 nonetheless inhibits cell activation by endotoxin. These findings suggest that binding of endotoxin to cell-surface CD14 is followed by subsequent interactions of the endotoxin-CD14 complex with additional membrane component(s) that enable transmembrane signaling. This function of CD14 may be prototypic for other members of the glycosyl-phosphatidylinositol-anchored family of proteins that do not play a primary role in signal ...
Longevity is correlated with stress resistance in many animal models. However, previous efforts through the boosting of the antioxidant defense system did not extend life span, suggesting that longevity related stress resistance is mediated by other uncharacterized pathways. We have developed a high-throughput platform for screening and rapid identification of novel genetic mutants in the mouse that are stress-resistant. Selection for resistance to stressors occurs in mutagenized mouse embryonic stem (ES) cells, which are carefully treated so as to maintain pluripotency for mouse production. Initial characterization of these mutant ES cells revealed mutations in Pigl, Tiam1, and Rffl, among others. These genes are implicated in glycosylphosphatidylinositol biosynthesis, NADPH oxidase function, and inflammation. These mutants: (1) are resistant to two different oxidative stressors, paraquat and the omission of 2-mercaptoethanol, (2) have reduced levels of endogenous reactive oxygen species (ROS),
Activated microglia are associated with deposits of aggregated proteins within the brains of patients with Alzheimers disease (AD), Parkinsons disease (PD) and prion diseases. Since the cytokines secreted from activated microglia are thought to contribute to the pathogenesis of these neurodegenerative diseases, compounds that suppress cytokine production have been identified as potential therapeutic targets. CD14 is a glycosylphosphatidylinositol (GPI)- anchored protein that is part of a receptor complex that mediates microglial responses to peptides that accumulate in prion disease (PrP82-146), AD (amyloid-β (Aβ)42) and PD (α-synuclein (αSN)). As some GPI-anchored proteins are released from cells by treatment with glimepiride, a sulphonylurea used for the treatment of diabetes, the effects of glimepiride upon CD14 expression and cytokine production from cultured macrophages were studied. RAW 264 cells and microglial cells were treated with glimepiride or phosphatidylinositol (PI)-phospholipase C
Elortza, Felix et al "Proteomic analysis of glycosylphosphatidylinositol-anchored membrane proteins." Molecular & Cellular Proteomics (2003): . Web. 06 July. 2020. ...
This Ebook aims to review basic understandings and give current opinions about several important aspects of glycosylphosphatidylinositol-anchored (GPI) protein biology from leading experts in this exciting and emerging field. The scope ranges from micro-domain localization and signaling to proteomics aspects, biophysical behavior through trans-cellular mobility to chemical synthesis of GPI mimics and finally modification of multi-scaled membrane surfaces and potential medical and biotech uses. The applied slant makes it very useful to the current state of knowledge. It is hoped that it will prove to be of considerable interest to students and researchers in this field.. ...
Aberrations in the glycosylphosphatidylinositol (GPI)-anchor biosynthesis pathway constitute a subclass of congenital disorders of glycosylation, and mutations in seven genes involved in this pathway have been identified. Among them, mutations in PIGV and PIGO, which are involved in the late stages of GPI-anchor synthesis, and PGAP2, which is involved in fatty-acid GPI-anchor remodeling, are all causative for hyperphosphatasia with mental retardation syndrome (HPMRS). Using whole exome sequencing, we identified novel compound heterozygous PIGO mutations (c.389C,A [p.Thr130Asn] and c.1288C,T [p.Gln430*]) in two siblings, one of them having epileptic encephalopathy. GPI-anchored proteins (CD16 and CD24) on blood granulocytes were slightly decreased compared with a control and his mother. Our patients lacked the characteristic features of HPMRS, such as facial dysmorphology (showing only a tented mouth) and hypoplasia of distal phalanges, and had only a mild elevation of serum alkaline phosphatase ...
Complete information for PIGA gene (Protein Coding), Phosphatidylinositol Glycan Anchor Biosynthesis Class A, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
An implanted intervertebral prosthesis includes first and second components adapted to attach to a first vertebra and a second vertebra, respectively, that define an intervertebral space. The prosthesis includes a first anchor structure on the first component adapted to enter a grove formed in the first vertebra, and a second anchor structure on the second component adapted to enter a grove formed in the second vertebra. The first anchor structure is offset from the second anchor structure to provide separation of the grooves to preserve vertebral thickness and avoid vertebral splitting. The offset anchor structures can be symmetrically disposed about a midline of the prosthesis or asymmetrically disposed about the midline. In some embodiments, the offset anchor structures comprise elongate anchors shaped as fins or keels. In other embodiments, the offset anchor structures comprise rows of pillars disposed in rows.
We investigated the influence of a glycosylphosphatidylinositol (GPI) anchor on the ectodomain of the influenza hemagglutinin (HA) by replacing the wild type (wt) transmembrane and cytoplasmic domains with a GPI lipid anchor. GPI-anchored HA (GPI-HA) was transported to the cell surface with equal efficiency and at the same rate as wt-HA. Like wt-HA, cell surface GPI-HA, and its ectodomain released with the enzyme PI-phospholipase C (PI-PLC), were 9S trimers. Compared to wt-HA, the GPI-HA ectodomain underwent additional terminal oligosaccharide modifications; some of these occurred near the receptor binding pocket and completely inhibited the ability of GPI-HA to bind erythrocytes. Growth of GPI-HA-expressing cells in the presence of the mannosidase I inhibitor deoxymannojirimycin (dMM) abrogated the differences in carbohydrate modification and restored the ability of GPI-HA to bind erythrocytes. The ectodomain of GPI-HA produced from cells grown in the presence or absence of dMM underwent ...
This gene encodes an enzyme involved in glycosylphosphatidylinositol-anchor biosynthesis. The encoded protein, which is localized to the endoplasmic reticulum, is involved in transferring ethanoloamine phosphate to mannose 2 of glycosylphosphatidylinositol species H7 to form species H8. Allelic variants of this gene have been associated with intellectual disability, hypotonia, and early-onset seizures. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016 ...
Many proteins are associated with the outer layer of the cell membrane through a posttranslationally added glycosyl phosphatidylinositol (GPI) anchor. The functional significance of this type of protein linkage is unclear, although it results in increased lateral mobility, sorting to the apical surface of the cell, reinsertion into cell membranes, and possibly cell signaling. Here evidence is presented that GPI-linked proteins can undergo intermembrane transfer in vivo. GPI-linked proteins expressed on the surface of transgenic mouse red blood cells were transferred in a functional form to endothelial cells in vivo. This feature of GPI linkage may be potentially useful for the delivery of therapeutic proteins to vascular endothelium ...
Strains of Escherichia coli persist within the human gut as normal commensals, but are frequent pathogens and can cause recurrent infection. Here we show that, in contrast to E. coli subjected to opsonic interactions stimulated by the hosts immune response, E. coli that bind to the macrophage surface exclusively through the bacterial lectin FimH can survive inside the cell following phagocytosis. This viability is largely due to the attenuation of intracellular free-radical release and of phagosome acidification during FimH-mediated internalization, both of which are triggered by antibody-mediated internalization. This different processing of non-opsonized bacteria is supported by morphological evidence of tight-fitting phagosomes compared with looser, antibody-mediated phagosomes. We propose that non-opsonized FimH-expressing E. coli co-opt internalization of lipid-rich microdomains following binding to the FimH receptor, the glycosylphosphatidylinositol-linked protein CD48, because (1) the sterol
In a biracial population of older adults, we have characterized the epidemiological and genetic associations of sCD14, as well as relationships of this inflammatory biomarker to incident CVD and mortality. Baseline sCD14 was correlated positively with EA ethnicity, female sex, traditional CVD risk factors (smoking, hypertension, diabetes mellitus), and other inflammatory biomarkers (IL-6, CRP, fibrinogen), and negatively correlated with BMI. We identified 2 genomewide significant sCD14-associated loci, the CD14 structural locus on chromosome 5q21 and a novel missense variant of PIGC, which encodes an enzyme required for the first step in GPI anchor biosynthesis. We also showed that sCD14 predicts incident CVD and mortality in older adults.. Using a combined GWAS and fine-mapping approach, we identified intra- and interpopulation allelic heterogeneity at the CD14 locus, including 2 new CD14 variants associated with lower sCD14 levels. The significant, nonredundant variants at the CD14 locus ...
This gene encodes an enzyme involved in glycosylphosphatidylinositol-anchor biosynthesis. The encoded protein, which is localized to the endoplasmic reticulum, is involved in transferring ethanoloamine phosphate to mannose 2 of glycosylphosphatidylinositol species H7 to form species H8. Allelic variants of this gene have been associated with intellectual disability, hypotonia, and early-onset seizures. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016] ...
A cold acclimation-responsive glycosylphosphatidylinositol-anchored protein (GPI-AP) influences the acquisition of freezing tolerance in Arabidopsis. 10th International Plant Cold Hardiness Seminar (Poznan, Poland ...
GPI-anchored surface proteins mediate many important functions, including transport, signal transduction, adhesion, and protection against complement. They cluster into glycolipid-based membrane domains and caveolae, plasmalemmal vesicles involved in the transcytosis and endocytosis of these surface proteins. However, in lymphocytes, neither the characteristic flask shaped caveolae nor caveolin, a transmembrane protein typical of caveolae, have been observed. Here, we show that the GPI-anchored CD59 molecule on Jurkat T cells is internalized after cross-linking, a process inhibited by nystatin, a sterol chelating agent. Clustered CD59 molecules mostly accumulate in non-coated invaginations of the lymphocyte membrane before endocytosis, in marked contrast with the pattern of CD3-TCR internalization. Cytochalasin H blocked CD59 internalization in lymphocytes, but neither CD3 internalization nor transferrin uptake. Confocal microscopy analysis of F-actin distribution within lymphocytes showed that ...
Insect-transmitted protozoan parasites cause widespread and debilitating diseases in man and domestic livestock throughout the tropics. Examples of diseases caused by trypanosomatid parasites include African sleeping sickness (caused by Trypanosoma brucei and transmitted by tsetse flies), Chagas disease (caused by Trypanosoma cruzi) and kala-azar, espundia and oriental sore (caused by the Leishmania). There are no vaccines against these diseases and most of the available drug treatments are toxic and/or ineffective.. Parasite surface molecules must protect the organisms and enable them to identify, and interact with, cells of both the insect vector and the animal host. Many trypanosomatid parasite surface molecules are either glycosylphosphatidylinositol (GPI) anchored glycoproteins or GPI-related glycolipids (Fig.1).. The parasite GPI biosynthetic pathway, and the pathways that assemble the sugar nucleotides that fuel it and the protein O- and N-glycosylation pathways, are validated targets for ...
Here you can find information to the course "Struktur und Reaktivität organische und bioorganische Verbindungen" at the Humboldt University. [more] ...
GPI Transamidase Subunit; Involved In Attachment Of Glycosylphosphatidylinositol (GPI) Anchors To Proteins; May Have A Role In Recognition Of The Attachment Signal Or Of The Lipid Portion Of GPI
Complete information for PIGV gene (Protein Coding), Phosphatidylinositol Glycan Anchor Biosynthesis Class V, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Glycosyl-phosphatidylinositol molecules of the parasite and the host - Volume 108 Issue S1 - M. A. J. Ferguson, J. S. Brimacombe, S. Cottaz, R. A. Field, L. S. Güther, S. W. Homans, M. J. McConville, A. Mehlert, K. G. Milne, J. E. Ralton, Y. A. Roy, P. Schneider, N. Zitzmann
The protein encoded by this gene plays a role in the maturation of glycosylphosphatidylinositol (GPI) anchors on GPI-anchored proteins. Defects in this gene have been associated with hyperphosphatasia with mental retardation syndrome 3. [provided by RefSeq, Oct 2016 ...
The proposal that GPI-anchored proteins form a heterodimeric membrane protein is novel. Previous work and current theories suggest that GPI-anchored glycoproteins are introduced into the plasma membrane as monomers, possibly in lipid shells, which then cluster in lipid rafts (Anderson and Jacobson, 2002; Harris and Siu, 2002). In some cases, this clustering can result in lateral associations, leading to dimer formation and the subsequent creation of higher-order oligomeric complexes. The Dictyostelium adhesion molecule gp80 oligomerizes in lipid rafts (Harris et al., 2001), and axonin-1 is thought to form an adhesion lattice by homophilic cis and trans interactions (Freigang et al., 2000; Kunz et al., 2002). The typical size and stability of lipid rafts is contentious, but recent proposals that rafts are less than 5 nm in size and contain three to four GPI-anchored proteins of more than one molecular species are particularly interesting and fit well with our data (Sharma et al., 2004). ...
GPAA1 antibody (glycosylphosphatidylinositol anchor attachment protein 1 homolog (yeast)) for IHC-P, WB. Anti-GPAA1 pAb (GTX115131) is tested in Human, Mouse samples. 100% Ab-Assurance.
Devices, methods and kits for restricting a portion of a GI tract by tightening tissue are provided. The devices, methods and kits can be used to treat GERD or obesity. The devices, methods, and kits do not require the formation of plications in tissue walls and may result in faster application, reduced surgical trauma, reduced risk, and reduced cost. The devices comprise a plurality of tissue-engageable anchors coupled to a tether. Each anchor is secured to a tissue wall of the GI tract. The anchors are secured to the tissue wall in a manner that may minimize tissue damage. The tether is configured to be cinched to draw the anchors together, which in turn draws the tissue secured to the anchors together, thereby tightening tissue to restrict a portion of the GI tract.
Clone REA810 recognizes the mouse granulocyte-differentiation antigen-1 (Gr-1) antigen, also known as Ly-6G, a 21-25 kDa, GPI-anchored cell surface protein. Cross-reactivity of Gr-1 with Ly-6C was not detected on hematopoietic cells that express Ly-6C and are negative for Ly-6G. Gr-1 is expressed on mature granulocytes in bone marrow and peripheral tissues. The Anti-Gr-1 antibody also stains monocytes transiently during their differentiation in bone marrow and at low levels plasmacytoid dendritic cells in lymphoid tissues. Additional information: Clone REA810 displays negligible binding to Fc receptors. - USA
MDGA1 overexpression lysate, 0.1 mg. Transient overexpression lysate of MAM domain containing glycosylphosphatidylinositol anchor 1 (MDGA1)
WordFez is a plugin for bilingual (French-English) posts. It is seamlessly integrated into WordPress using a TinyMCE plugin.. It will add 2 extra buttons in the WYSIWYG interface for French and English language. Each button inserts 2 anchors to surround each language. The anchors are labeled by small flags ...
THE home pennant has been run up to the masthead of several of the warships that have been cruising in different parts of the world for the past three years. Usually, only a small whip is placed on the fore truck, and when the anchors are weighed and the long pennant is run up, it means that the ship is to return to the home station ...
The CD16 antigen exists both as a glycosyl-phosphatidylinositol (GPI)-anchored protein in polymorphonuclear cells and as a transmembrane protein in NK cells.
Glycosylphosphatidylinositols (GPIs) are glycolipids described as toxins of protozoan parasites due to their inflammatory properties in mammalian hosts characterized by the production of interleukin (IL)-1, IL-12 and tumor necrosis factor (TNF)-α. In the present work, we studied the cytokines produced by antigen presenting cells in response to ten different GPI species extracted from Babesia divergens, responsible for babesiosis. Interestingly, B. divergens GPIs induced the production of anti-inflammatory cytokines (IL-2, IL-5) and of the regulatory cytokine IL-10 by macrophages and dendritic cells. In contrast to all protozoan GPIs studied until now, GPIs from B. divergens did not stimulate the production of TNF-α and IL-12, leading to a unique Th1/Th2 profile. Analysis of the carbohydrate composition of the B. divergens GPIs indicated that the di-mannose structure was different from the evolutionary conserved tri-mannose structure, which might explain the particular cytokine profile they ...
Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal bone marrow disorder, resulting from an acquired, somatic X-linked mutation of the PIG-A gene in an hematopoietic stem cell. Absence of PIG-A function in a cell prevents synthesis of the glycosylphosphatidylinositol (GPI) moiety, which anchors many different types of proteins to the cell membrane. Intravascular red cell destruction, the hallmark of the disorder, is caused by susceptibility of the abnormal erythrocyte to complement-mediated lysis; this sensitivity is due to lack of CD59, a potent inhibitor of the late components of complement and reactive lysis. In vitro studies from this laboratory have demonstrated transfer of GPI-linked proteins, CD55 and CD59, from normal to deficient cells and transfer is associated with resistance to hemolysis. Patients with PNH frequently require transfusion as their standard care. In addition, patients with all blood groups requiring transfusion will often receive compatible group O blood. Group O ...
Where do you work, what is your position and who is your advisor?. I work in the Department of Molecular Genetics at the University of Toronto. I am a Postdoc in Dr. Leah Cowens Laboratory.. Tell me about the project youre working on.. With GlycoNet, I am working on a translational project to develop a new broad-spectrum antifungal drug that kills pathogenic fungi, including species of Candida, Cryptococcus, and Aspergillus. Our compound, gepinacin, targets fungal glycosylphosphatidylinositol anchor biosynthesis, inhibiting growth and altering the fungal cell surface to expose immunostimulatory glycans. This project aims to improve pharmacokinetics of our scaffold by exploring SAR of gepinacin analogs, and to demonstrate efficacy in an animal model of candidiasis. Alongside this work, Im studying into the roles of fungal GPI-anchored proteins in host-pathogen interactions. Other than glycomics, what areas of research do you think is important in advancing healthcare?. Ill be very ...
GPI transamidase component PIG-T is an enzyme that in humans is encoded by the PIGT gene. This gene encodes a protein that is involved in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor is a glycolipid found on many blood cells and serves to anchor proteins to the cell surface. This protein is an essential component of the multisubunit enzyme, GPI transamidase. GPI transamidase mediates GPI anchoring in the endoplasmic reticulum, by catalyzing the transfer of fully assembled GPI units to proteins. PIGT has been shown to interact with PIGK and GPAA1. GRCh38: Ensembl release 89: ENSG00000124155 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000017721 - Ensembl, May 2017 "Human PubMed Reference:". "Mouse PubMed Reference:". Vainauskas S, Menon AK (Apr 2005). "Endoplasmic reticulum localization of Gaa1 and PIG-T, subunits of the glycosylphosphatidylinositol transamidase complex". J Biol Chem. 280 (16): 16402-9. doi:10.1074/jbc.M414253200. PMID 15713669. "Entrez Gene: ...
Once suspected, the diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) is straightforward when flow cytometric analysis of the peripheral blood reveals a population of glycosyl phosphatidylinositol anchor protein-deficient cells. But PNH is clinically heterogeneous, with some patients having a disease process characterized by florid intravascular, complement-mediated hemolysis, whereas in others, bone marrow failure dominates the clinical picture with modest or even no evidence of hemolysis observed.
Blood 1998 Dec 1;92(11):4439-45 Abstract quote Hemolytic anemia is a major feature of paroxysmal nocturnal hemoglobinuria (PNH). Intravascular red blood cell (RBC) destruction is caused by increased sensitivity of the abnormal erythrocyte to complement-mediated lysis, due to the GPI absence of a membrane-bound glycosylphosphatidylinositol (GPI)-linked protein, which functions as an inhibitor of reactive lysis (CD59). Both in vivo and in vitro models have suggested the feasibility of cell-to-cell transfer of GPI proteins, and patients with hemolysis could potentially benefit from transfer of CD59 to their deficient erythrocytes. We studied the ability of RBC components prepared from outdated packed RBC collections, as well as high-density lipoprotein (HDL) preparations, rich in CD55 and CD59, to promote protein transfer, as assessed by flow cytometry, immunoblotting, and susceptibility to complement-mediated lysis. By flow cytometry, CD55 and CD59 were present on RBC-derived microvesicles that ...
1516 Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver, and the third most common cause of cancer-related mortality. Currently, there are not effective treatments for HCCs that cannot be removed by surgery. Work from our laboratory and from other groups has demonstrated that glypican-3 (GPC3) is expressed by most HCCs (~ 75 %), while it is undetectable in hepatocytes from normal liver and benign liver disease. GPC3 is a member of the glypican family. Glypicans are heparan sulfate proteoglycans that are bound to the exocytoplasmic surface of the plasma membrane through a glycosyl-phosphatidylinositol anchor. Experimental evidence accumulated during the last few years indicates that glypicans regulate the activity of several signaling pathways, including those triggered by Wnts, Hedgehogs, BMPs and FGFs. This regulatory activity is based on the ability of glypicans to facilitate or inhibit the interaction of these ligands with their signaling receptors. Our ...
陣發性夜間血紅素尿症(paroxysmal nocturnal haemoglobinuria, PNH)是一種罕見的造血幹細胞疾病,因後天基因突變而造成[1]。一般來說,正常紅血球的細胞膜上有幾種保護性蛋白質,例如:蛋白衰變加速因子(decay accelerating factor, CD55)以及溶解細胞膜抑制物(membrane inhibitor of reactive lysis, CD59),使紅血球不會因補體(免疫系統的一部分)的攻擊而破裂[1]。然而,PNH患者因為在X染色體上的phosphatidylinositol glycan A (PIG-A)基因發生突變,造成某些醣脂質,例如glycosylphosphatidylinositols (GPI)無法形成,而使紅血球上的保護性蛋白質無法藉著GPI結合在紅血球的細胞膜上[1]。紅血球沒有這些蛋白質的保護就容易因人體內補體系統的攻擊而破裂,引起持續、慢性的血管內溶血性疾病,這也是造成疾病症狀及後續嚴重併發症的原因[2-4 ...
GPI-Anchored Proteins. The majority of eukaryotic cell membrane proteins have hydrophobic amino acids stretches that consists of a transmembrane polypeptide chain, which embeds the proteins into phospholipids double layer of the membrane [18]. GPI anchored proteins are membrane bound proteins. Several proteins are linked to the outer cell membrane leaflet by GPI anchor. This structure involves three key elements: a core containing a phosphatidylinositol (PI) moiety, one glucosamine and three mannose molecules and one ethanolamine phosphate unit [19]. A peptide bond links the C-terminus of the protein polypeptide to the last moiety. The GPI-anchor is created in the endoplasmic reticulum and attached to the polypeptide post-translational by a transaminase enzyme [20-21]. Molecular Genetic Background. Until date, all PNH patients have had genetic mutations in an X-linked gene known as PIG-A [22, 23,9]. The PIG-A gene product is initially required in the assembly of GPI anchors [24]. Consequently, a ...
Lien vers Pubmed [PMID] - 15337781. J. Cell Biol. 2004 Aug;166(5):743-53. Listeria monocytogenes uptake by nonphagocytic cells is promoted by the bacterial invasion proteins internalin and InlB, which bind to their host receptors E-cadherin and hepatocyte growth factor receptor (HGF-R)/Met, respectively. Here, we present evidence that plasma membrane organization in lipid domains is critical for Listeria uptake. Cholesterol depletion by methyl-beta-cyclodextrin reversibly inhibited Listeria entry. Lipid raft markers, such as glycosylphosphatidylinositol-linked proteins, a myristoylated and palmitoylated peptide and the ganglioside GM1 were recruited at the bacterial entry site. We analyzed which molecular events require membrane cholesterol and found that the presence of E-cadherin in lipid domains was necessary for initial interaction with internalin to promote bacterial entry. In contrast, the initial interaction of InlB with HGF-R did not require membrane cholesterol, whereas downstream ...
The tectorial membrane is an extracellular matrix lying over the apical surface of the auditory epithelium. Immunofluorescence studies have suggested that some proteins of the avian tectorial membrane, the tectorins, may be unique to the inner ear (Killick, R., C. Malenczak, and G. P. Richardson. 1992. Hearing Res. 64:21-38). The cDNA and deduced amino acid sequences for chick beta-tectorin are presented. The cDNA encodes a protein of 36,902.6 D with a putative signal sequence, four potential N-glycosylation sites, 13 cysteines, and a hydrophobic COOH terminus. Western blots of two-dimensional gels using antibodies to a synthetic peptide confirm the identity of the cDNA. Southern and Northern analysis suggests that beta-tectorin is a single-copy gene only expressed in the inner ear. The predicted COOH terminus is similar to that of glycosylphosphatidylinositol-linked proteins, and antisera raised to this region react with in vitro translation products of the cDNA clone but not with mature ...
Clone REA465 recognizes the human CD157 antigen, a glycosylphosphatidylinositol (GPI) linked protein, which is also known as bone marrow stromal antigen 1 (BST-1) or cyclic ADP-ribose hydrolase 2. CD157, a member of the CD38 gene family, is an NAD-metabolizing ectoenzyme and a signaling molecule, which synthesizes the second messengers cyclic ADP-ribose and nicotinate-adenine dinucleotide phosphate, former a second messenger that elicits calcium release from intracellular stores. It is mainly expressed by cells of the myeloid lineage, bone marrow stroma, and vascular endothelium. CD157 is also expressed by ovarian cancer epithelium and by peritoneal mesothelial cells, where it is implicated in tumor dissemination. Further, it is endowed with receptor-like features observed in different cell types and transduces signals by interacting with transmembrane partner molecules, a strategy shared by other GPI-anchored molecules. CD157 is involved in neutrophil polarization, adhesion, and motility and controls