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GPI-linked protein

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https://www.readbyqxmd.com/read/29098723/establishing-a-novel-pig-a-gene-mutation-assay-in-l5178ytk-mouse-lymphoma-cells
#1
Yiying Wang, Javier Revollo, Page McKinzie, Mason G Pearce, Azra Dad, Berran Yucesoy, Hans Rosenfeldt, Robert H Heflich, Vasily N Dobrovolsky
The X-linked Pig-a gene encodes an enzyme required for the biosynthesis of glycosyl phosphatidylinositol (GPI) anchors. Pig-a mutant cells fail to synthesize GPI and to express GPI-anchored protein markers (e.g., CD90) on their surface. Marker deficiency serves as a phenotypic indicator of Pig-a mutation in various in vivo assays. Here, we describe an in vitro Pig-a mutation assay in L5178YTk(+/-) mouse lymphoma cells, in which mutant-phenotype cells are measured by flow cytometry using a fluorescent anti-CD90 antibody...
November 2, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29075054/diagnosis-of-paroxysmal-nocturnal-hemoglobinuria-recent-advances
#2
REVIEW
Prabhu Manivannan, Ankur Ahuja, Hara Prasad Pati
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disorder with its protean clinical manifestations. This is due to partial or complete absence of 'glycophosphatidyl-inositol-anchor proteins' (GPI-AP). The main aim of this review is to highlight various diagnostic modalities available, basic principle of each test and recent advances in the diagnosis of PNH. Recently among various tests available, the flow cytometry has become 'the gold standard' for PNH testing. In order to overcome the difficulties encountered by the testing and research laboratories throughout the world, International Clinical Cytometry Society has come up with guidelines regarding the indications for testing, protocol for sample collection, processing, panel of antibodies as well as gating strategies to be used, how to interpret the test and reporting format to be used...
December 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/29020444/biologically-complex-planar-cell-plasma-membranes-supported-on-polyelectrolyte-cushions-enhance-transmembrane-protein-mobility-and-retain-native-orientation
#3
Han-Yuan Liu, Wei-Liang Chen, Christopher K Ober, Susan Daniel
Reconstituted supported lipid bilayers (SLB) are widely used as in vitro cell-surface models because they are compatible with a variety of surface-based analytical techniques. However, one of the challenges of using SLBs as a model of the cell surface is the limited complexity in membrane composition, including the incorporation of transmembrane proteins and lipid diversity that may impact the activity of those proteins. Additionally, it is challenging to preserve the transmembrane protein native orientation, function, and mobility in SLBs...
October 24, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28950949/g-protein-coupled-kinin-receptors-and-immunity-against-pathogens
#4
Julio Scharfstein, Pablo I P Ramos, Manoel Barral-Netto
For decades, immunologists have considered the complement system as a paradigm of a proteolytic cascade that, acting cooperatively with the immune system, enhances host defense against infectious organisms. In recent years, advances made in thrombosis research disclosed a functional link between activated neutrophils, monocytes, and platelet-driven thrombogenesis. Forging a physical barrier, the fibrin scaffolds generated by synergism between the extrinsic and intrinsic (contact) pathways of coagulation entrap microbes within microvessels, limiting the systemic spread of infection while enhancing the clearance of pathogens by activated leukocytes...
2017: Advances in Immunology
https://www.readbyqxmd.com/read/28930438/supported-planar-mammalian-membranes-as-models-of-in-vivo-cell-surface-architectures
#5
Han-Yuan Liu, Hannah Grant, Hung-Lun Hsu, Raya Sorkin, Filip Bošković, Gijs Wuite, Susan Daniel
Emerging technologies use cell plasma membrane vesicles or "blebs" as an intermediate to form molecularly complete, planar cell surface mimetics that are compatible with a variety of characterization tools and microscopy methods. This approach enables direct incorporation of membrane proteins into supported lipid bilayers without using detergents and reconstitution and preserves native lipids and membrane species. Such a system can be advantageous as in vitro models of in vivo cell surfaces for study of the roles of membrane proteins as drug targets in drug delivery, host-pathogen interactions, tissue engineering, and many other bioanalytical and sensing applications...
October 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28861787/analysis-of-cellular-prion-protein-endoproteolytic-processing
#6
Victoria Lewis
Like numerous proteins of various structural and functional classes, the glycosylphosphatidylinositol (GPI)-anchored cellular prion protein (PrP(C)) has been recognized to undergo endoproteolytic processing for decades, a phenomenon observed in various cultured cell lines, as well as human and several animal tissue extracts. Despite this, the physiological significance of PrP(C) proteolytic cleavage has not yet been entirely elucidated. Experimental evidence suggests independent normal biological functions of the full-length and truncated PrP(C) species, as well as probable links of endoproteolysis to prion disease transmission susceptibility, pathogenesis, and toxicity...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28838671/biochemical-characterization-of-prions
#7
Michele Fiorini, Matilde Bongianni, Salvatore Monaco, Gianluigi Zanusso
Prion disease or transmissible spongiform encephalopathies are characterized by the presence of the abnormal form of the prion protein (PrP(Sc)). The pathological and transmissible properties of PrP(Sc) are enciphered in its secondary and tertiary structures. Since it's well established that different strains of prions are linked to different conformations of PrP(Sc), biochemical characterization of prions seems a preliminary but reliable approach to detect, analyze, and compare prion strains. Experimental biochemical procedures might be helpful in distinguishing PrP(Sc) physicochemical properties and include resistance to proteinase K (PK) digestion, insolubility in nonionic detergents, PK-resistance under denaturing conditions and sedimentation properties in sucrose gradients...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28830553/immunogenicity-of-glycosylphosphatidylinositol-anchored-micronemal-antigen-in-natural-plasmodium-vivax-exposure
#8
Siriruk Changrob, Jin-Hee Han, Kwon-Soo Ha, Won Sun Park, Seok-Ho Hong, Patchanee Chootong, Eun-Taek Han
BACKGROUND: Plasmodium vivax is the most geographically widespread malaria species and codominates with Plasmodium falciparum, the deadliest form of the malaria parasite. For the last few years, the number of vivax malaria cases has increased, but vivax malaria is still considered a neglected disease. During the blood stages of their life cycle, P. vivax parasites export several hundred proteins into host red blood cells. Some of these exported proteins have been discovered and studied for use as a blood-stage malaria vaccine...
August 22, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28739265/role-of-adam10-in-intestinal-crypt-homeostasis-and-tumorigenesis
#9
Peter J Dempsey
A disintegrin and metalloproteinases (ADAMs) are a family of mSultidomain, membrane-anchored proteases that regulate diverse cellular functions, including cell adhesion, migration, proteolysis and other cell signaling events. Catalytically-active ADAMs act as ectodomain sheddases that proteolytically cleave type I and type II transmembrane proteins and some GPI-anchored proteins from the cellular surface. ADAMs can also modulate other cellular signaling events through a process known as regulated intramembrane proteolysis (RIP)...
November 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28694219/hepatic-abca1-deficiency-is-associated-with-delayed-apolipoprotein-b-secretory-trafficking-and-augmented-vldl-triglyceride-secretion
#10
Mingxia Liu, Soonkyu Chung, Gregory S Shelness, John S Parks
ATP binding cassette transporter A1 (ABCA1) is a membrane transporter that facilitates nascent HDL formation. Tangier disease subjects with complete ABCA1 deficiency have <5% of normal levels of plasma HDL, elevated triglycerides (TGs), and defective vesicular trafficking in fibroblasts and macrophages. Hepatocyte-specific ABCA1 knockout mice (HSKO) have a similar lipid phenotype with 20% of normal plasma HDL levels and a two-fold elevation of plasma TGs due to hepatic overproduction of large, triglyceride-enriched VLDL...
October 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28676667/eimeria-tenella-protein-trafficking-differential-regulation-of-secretion-versus-surface-tethering-during-the-life-cycle
#11
V Marugan-Hernandez, E Long, D Blake, C Crouch, F Tomley
Eimeria spp. are intracellular parasites that have a major impact on poultry. Effective live vaccines are available and the development of reverse genetic technologies has raised the prospect of using Eimeria spp. as recombinant vectors to express additional immunoprotective antigens. To study the ability of Eimeria to secrete foreign antigens or display them on the surface of the sporozoite, transiently transfected populations of E. tenella expressing the fluorescent protein mCherry, linked to endogenous signal peptide (SP) and glycophosphatidylinositol-anchor (GPI) sequences, were examined...
July 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28674079/nuclear-cd24-drives-tumor-growth-and-is-predictive-of-poor-patient-prognosis
#12
Jason E Duex, Charles Owens, Ana Chauca-Diaz, Garrett M Dancik, Lauren A Vanderlinden, Debashis Ghosh, Mariah Z Leivo, Donna E Hansel, Dan Theodorescu
Elevated tumor expression of the cell surface GPI-linked CD24 protein signals poor patient prognosis in many tumor types. However, some cancer cells selected to be negative for surface CD24 (surCD24(-)) still retain aggressive phenotypes in vitro and in vivo Here, we resolve this apparent paradox with the discovery of biologically active, nuclear CD24 (nucCD24) and finding that its levels are unchanged in surCD24(-) cells. Using the complementary techniques of biochemical cellular fractionation and immunofluorescence, we demonstrate a signal for CD24 in the nucleus in cells from various histologic types of cancer...
September 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28660664/engaging-ly-6a-sca-1-triggers-lipid-raft-dependent-and-independent-responses-in-cd4-t-cell-lines
#13
Melissa A Lang, Sultan A Jenkins, Phillip Balzano, Adeyinka Owoyele, Akshay Patel, Anil K Bamezai
INTRODUCTION: The lymphocyte antigen 6 (Ly-6) supergene family encodes proteins of 12-14 kda in molecular mass that are either secreted or anchored to the plasma membrane through a glycosyl-phosphatidylinisotol (GPI) lipid anchor at the carboxy-terminus. The lipidated GPI-anchor allows localization of Ly-6 proteins to the 10-100 nm cholesterol-rich nano-domains on the membrane, also known as lipid rafts. Ly-6A/Sca-1, a member of Ly-6 gene family is known to transduce signals despite the absence of transmembrane and cytoplasmic domains...
June 28, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28616799/dolichol-phosphate-mannose-synthase-a-glycosyltransferase-with-unity-in-molecular-diversities
#14
REVIEW
Dipak K Banerjee, Zhenbo Zhang, Krishna Baksi, Jesús E Serrano-Negrón
N-glycans provide structural and functional stability to asparagine-linked (N-linked) glycoproteins, and add flexibility. Glycan biosynthesis is elaborative, multi-compartmental and involves many glycosyltransferases. Failure to assemble N-glycans leads to phenotypic changes developing infection, cancer, congenital disorders of glycosylation (CDGs) among others. Biosynthesis of N-glycans begins at the endoplasmic reticulum (ER) with the assembly of dolichol-linked tetra-decasaccharide (Glc3Man9GlcNAc2-PP-Dol) where dolichol phosphate mannose synthase (DPMS) plays a central role...
August 2017: Glycoconjugate Journal
https://www.readbyqxmd.com/read/28581210/reduced-cell-surface-levels-of-gpi-linked-markers-in-a-new-case-with-pigg-loss-of-function
#15
Jin James Zhao, Jonatan Halvardson, Alexej Knaus, Patrik Georgii-Hemming, Peter Baeck, Peter M Krawitz, Ann-Charlotte Thuresson, Lars Feuk
Glycosylphosphatidylinositol (GPI) is a glycolipid that tethers more than 150 different proteins to the cell surface. Aberrations in biosynthesis of GPI anchors cause congenital disorders of glycosylation with clinical features including intellectual disability (ID), seizures, and facial dysmorphism. Here, we present two siblings with ID, cerebellar hypoplasia, cerebellar ataxia, early-onset seizures, and minor facial dysmorphology. Using exome sequencing, we identified a homozygous nonsense variant (NM_001127178...
June 5, 2017: Human Mutation
https://www.readbyqxmd.com/read/28576860/coordination-of-heparan-sulfate-proteoglycans-with-wnt-signaling-to-control-cellular-migrations-and-positioning-in-caenorhabditis-elegans
#16
Kristian Saied-Santiago, Robert A Townley, John D Attonito, Dayse S da Cunha, Carlos A Díaz-Balzac, Eillen Tecle, Hannes E Bülow
Heparan sulfates (HS) are linear polysaccharides with complex modification patterns, which are covalently bound via conserved attachment sites to core proteins to form heparan sulfate proteoglycans (HSPGs). HSPGs regulate many aspects of the development and function of the nervous system, including cell migration, morphology, and network connectivity. HSPGs function as cofactors for multiple signaling pathways, including the Wnt-signaling molecules and their Frizzled receptors. To investigate the functional interactions among the HSPG and Wnt networks, we conducted genetic analyses of each, and also between these networks using five cellular migrations in the nematode Caenorhabditis elegans We find that HSPG core proteins act genetically in a combinatorial fashion dependent on the cellular contexts...
August 2017: Genetics
https://www.readbyqxmd.com/read/28518050/acetylcholinesterase-provides-new-insights-into-red-blood-cell-ageing-in-vivo-and-in-vitro
#17
Joames K Freitas Leal, Merel J W Adjobo-Hermans, Roland Brock, Giel J C G M Bosman
BACKGROUND: During its 120 days sojourn in the circulation, the red blood cell (RBC) remodels its membrane. Acetylcholinesterase (AChE) is a glycosylphosphatidylinositol (GPI)-linked enzyme that may serve as a marker for membrane processes occurring this ageing-associated remodelling process. MATERIALS AND METHODS: Expression and enzymatic activity of AChE were determined on RBCs of various ages, as obtained by separation based on volume and density (ageing in vivo), and on RBCs of various times of storage in blood bank conditions (ageing in vitro), as well as on RBC-derived vesicles...
May 2017: Blood Transfusion, Trasfusione del Sangue
https://www.readbyqxmd.com/read/28490634/inflammatory-cytokines-down-regulate-the-barrier-protective-prostasin-matriptase-proteolytic-cascade-early-in-experimental-colitis
#18
Marguerite S Buzza, Tierra A Johnson, Gregory D Conway, Erik W Martin, Subhradip Mukhopadhyay, Terez Shea-Donohue, Toni M Antalis
Compromised gastrointestinal barrier function is strongly associated with the progressive and destructive pathologies of the two main forms of irritable bowel disease (IBD), ulcerative colitis (UC), and Crohn's disease (CD). Matriptase is a membrane-anchored serine protease encoded by suppression of tumorigenicity-14 (ST14) gene, which is critical for epithelial barrier development and homeostasis. Matriptase barrier-protective activity is linked with the glycosylphosphatidylinositol (GPI)-anchored serine protease prostasin, which is a co-factor for matriptase zymogen activation...
June 30, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28484166/molecular-genetics-biochemistry-and-biology-of-pnh
#19
Taroh Kinoshita
Paroxysmal nocturnal hemoglobinuria (PNH) manifests by clonal expansion of mutant hematopoietic stem cells (HSCs) bearing a somatic mutation in the X-linked PIGA gene. PIGA mutations cause defective biosynthesis of GPI and cell surface deficiency of GPI-anchored proteins such as DAF and CD59, leading to intravascular hemolysis and thrombosis. These two major symptoms of PNH can be controlled by eculizumab, an anti-C5 monoclonal antibody. Bone marrow failure, the third major symptom of PNH, is autoimmune-mediated and contributes to the clonal expansion of GPI-defective HSCs by selectively attacking GPI-positive wild-type HSCs...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28473293/moesin-and-merlin-regulate-urokinase-receptor-dependent-endothelial-cell-migration-adhesion-and-angiogenesis
#20
Bernard Degryse, Mishan Britto, Chun Xu Shan, Robert G Wallace, Keith D Rochfort, Philip M Cummins, Gerardene Meade, Ronan P Murphy
The glycosyl-phosphatidyl-inositol (GPI)-anchored urokinase receptor (uPAR) has no intracellular domain, but nevertheless initiates signalling through proximal interactions with other membrane receptors including integrins. The relationships between uPAR and ezrin/radixin/moesin (ERM) proteins, moesin and merlin have never been explored. Moesin and merlin are versatile membrane-actin links and regulators of receptors signalling, respectively. We show that uPAR controls moesin and merlin, which propagate uPAR-initiated signals and modulate integrin functions, thereby regulating uPAR activity...
July 2017: International Journal of Biochemistry & Cell Biology
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