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GPI-linked protein

Li-Na Wang, Mei-Hua Gao, Bing Wang, Bei-Bei Cong, Shu-Chao Zhang
Cluster of differentiation 59 (CD59) is a glycosylphosphatidylinositol-anchored protein. Cross-linking of CD59 with specific monoclonal antibodies can cause a series of intracellular signal transduction events. However, the underlying molecular mechanisms are poorly understood. Linker for activation of T-cells (LAT) is a crucial adaptor protein in T-cell signaling, and its phosphorylation and palmitoylation are essential for its localization and function. In a previous study by the present authors, it was demonstrated that CD59 may be responsible for LAT palmitoylation, thereby regulating T-cell signal transduction...
April 2018: Oncology Letters
Ambadi Thody Sabareesan, M K Mathew, Jayant B Udgaonkar
The cellular prion protein (PrPC ), which is present ubiquitously in all mammalian neurons, is normally found to be linked to the cell membrane through a glycosylphosphatidylinositol (GPI) anchor. The conformational conversion of PrPC into misfolded and aggregated forms is associated with transmissible neurodegenerative diseases known as prion diseases. The importance of different misfolded conformations in prion diseases, and the mechanism by which prion aggregates induce neurotoxicity remain poorly understood...
March 4, 2018: Biochimica et Biophysica Acta
Michael B Langford, Jennifer E Outhwaite, Martha Hughes, David R C Natale, David G Simmons
Fetal growth and survival is dependent on the elaboration and propinquity of the fetal and maternal circulations within the placenta. Central to this is the formation of the interhaemal membrane, a multi-cellular lamina facilitating exchange of oxygen, nutrients and metabolic waste products between the mother and fetus. In rodents, this cellular barrier contains two transporting layers of syncytiotrophoblast, which are multinucleated cells that form by cell-cell fusion. Previously, we reported the expression of the GPI-linked cell surface protein LY6E by the syncytial layer closest to the maternal sinusoids of the mouse placenta (syncytiotrophoblast layer I)...
March 2, 2018: Scientific Reports
Huaimin Wang, Zhaoqianqi Feng, Steven J Del Signore, Avital A Rodal, Bing Xu
Despite the advancement of molecular imaging techniques, there is an unmet need of probes for directly imaging membrane dynamics of live cells. Here we report a novel type of active (or enzyme responsive) probes to directly image membrane dynamics of live cells with high spatial and temporal resolution over extended timescales and areas. Because lipid rafts enrich cholesterols and GPI-anchored enzymes (e.g., ectophosphatases), we design probes that consist of an enzymatic trigger, a fluorophore, and a cholesterol and exhibit high affinity for lipid rafts...
February 26, 2018: Journal of the American Chemical Society
Toktam Abbasnia, Ahmad Asoodeh, Gholamreza Habibi, Alireza Haghparast
BACKGROUND: Tropical theileriosis is widely distributed from North Africa to East Asia. It is a tick-borne disease caused by Theileria annulata, an obligate two-host intracellular protozoan parasite of cattle. Theileria annulata use leukocytes and red blood cells for completion of the life-cycle in mammalian hosts. The stage of Theileria annulata in monocytes and B lymphocytes of cattle is an important step in pathogenicity and diagnosis of the disease. Glycosylphosphatidylinositols (GPIs) are a distinct class of glycolipid structures found in eukaryotic cells and are implicated in several biological functions...
February 6, 2018: Parasites & Vectors
Rhiannon David, Emily Talbot, Bethany Allen, Amy Wilson, Usman Arshad, Ann Doherty
A recent flow cytometry-based in vivo mutagenicity assay involves the hemizygous phosphatidylinositol class A (Pig-a) gene. Pig-a forms the catalytic subunit of N-acetylglucosaminyltransferase required for glycophosphatidylinositol (GPI) anchor biosynthesis. Mutations in Pig-a prevent GPI-anchor synthesis resulting in loss of cell-surface GPI-linked proteins. The aim of the current study was to develop and validate an in vitro Pig-a assay in L5178Y mouse lymphoma cells. Ethyl methanesulfonate (EMS)-treated cells (186...
January 23, 2018: Archives of Toxicology
Kazuya Miyashita, Isamu Fukamachi, Manabu Nagao, Tatsuro Ishida, Junji Kobayashi, Tetsuo Machida, Kiyomi Nakajima, Masami Murakami, Michael Ploug, Anne P Beigneux, Stephen G Young, Katsuyuki Nakajima
BACKGROUND: Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1), a glycosylphosphatidylinositol (GPI)-anchored protein of capillary endothelial cells, transports lipoprotein lipase to the capillary lumen and is essential for the lipolytic processing of triglyceride-rich lipoproteins. OBJECTIVE: Because some GPI-anchored proteins have been detected in plasma, we tested whether GPIHBP1 is present in human blood and whether GPIHBP1 deficiency or a history of cardiovascular disease affected GPIHBP1 circulating levels...
November 1, 2017: Journal of Clinical Lipidology
Justyna Sobocińska, Paula Roszczenko-Jasińska, Monika Zaręba-Kozioł, Aneta Hromada-Judycka, Orest V Matveichuk, Gabriela Traczyk, Katarzyna Łukasiuk, Katarzyna Kwiatkowska
Lipopolysaccharide (LPS) is a component of the outer membrane of Gram-negative bacteria that induces strong proinflammatory reactions of mammals. These processes are triggered upon sequential binding of LPS to CD14, a GPI-linked plasma membrane raft protein, and to the TLR4/MD2 receptor complex. We have found earlier that upon LPS binding, CD14 triggers generation of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2 ], a lipid controlling subsequent proinflammatory cytokine production. Here we show that stimulation of RAW264 macrophage-like cells with LPS induces global changes of the level of fatty-acylated, most likely palmitoylated, proteins...
February 2018: Molecular & Cellular Proteomics: MCP
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
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
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
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
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
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
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
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
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
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
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
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
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