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GPI-linked protein

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https://www.readbyqxmd.com/read/28332730/multicenter-validation-of-a-simplified-method-for-paroxysmal-nocturnal-hemoglobinuria-screening
#1
Arianna Gatti, Luigi Del Vecchio, Massimo Geuna, Matteo G Della Porta, Bruno Brando
According to the most credited and validated international guidelines, testing peripheral blood for the diagnosis of PNH is best accomplished with four color, two tubes or five to six color, single tube flow cytometric (FCM) procedures, with the demonstration of the deficiency of at least two GPI-linked surface proteins in two different cell subsets to corroborate the diagnosis (1-7). Each one of these state-of-the-art techniques ensure a high degree of sensitivity (i.e. down to 0.01% PNH granulocyte or red cell clones) with a high level of standardization and good reproducibility...
March 23, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28327575/analysis-of-exome-data-for-4293-trios-suggests-gpi-anchor-biogenesis-defects-are-a-rare-cause-of-developmental-disorders
#2
Alistair T Pagnamenta, Yoshiko Murakami, John M Taylor, Consuelo Anzilotti, Malcolm F Howard, Venessa Miller, Diana S Johnson, Shereen Tadros, Sahar Mansour, I Karen Temple, Rachel Firth, Elisabeth Rosser, Rachel E Harrison, Bronwen Kerr, Niko Popitsch, Taroh Kinoshita, Jenny C Taylor, Usha Kini
Over 150 different proteins attach to the plasma membrane using glycosylphosphatidylinositol (GPI) anchors. Mutations in 18 genes that encode components of GPI-anchor biogenesis result in a phenotypic spectrum that includes learning disability, epilepsy, microcephaly, congenital malformations and mild dysmorphic features. To determine the incidence of GPI-anchor defects, we analysed the exome data from 4293 parent-child trios recruited to the Deciphering Developmental Disorders (DDD) study. All probands recruited had a neurodevelopmental disorder...
March 22, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28272426/post-translational-modifications-in-prp-expand-the-conformational-diversity-of-prions-in-vivo
#3
Patricia Aguilar-Calvo, Xiangzhu Xiao, Cyrus Bett, Hasier Eraña, Katrin Soldau, Joaquin Castilla, K Peter R Nilsson, Witold K Surewicz, Christina J Sigurdson
Misfolded prion protein aggregates (PrP(Sc)) show remarkable structural diversity and are associated with highly variable disease phenotypes. Similarly, other proteins, including amyloid-β, tau, α-synuclein, and serum amyloid A, misfold into distinct conformers linked to different clinical diseases through poorly understood mechanisms. Here we use mice expressing glycophosphatidylinositol (GPI)-anchorless prion protein, PrP(C), together with hydrogen-deuterium exchange coupled with mass spectrometry (HXMS) and a battery of biochemical and biophysical tools to investigate how post-translational modifications impact the aggregated prion protein properties and disease phenotype...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28187452/pign-gene-expression-aberration-is-associated-with-genomic-instability-and-leukemic-progression-in-acute-myeloid-leukemia-with-myelodysplastic-features
#4
Emmanuel K Teye, Abigail Sido, Ping Xin, Niklas K Finnberg, Prashanth Gokare, Yuka I Kawasawa, Anna C Salzberg, Sara Shimko, Michael Bayerl, W Christopher Ehmann, David F Claxton, Witold B Rybka, Joseph J Drabick, Hong-Gang Wang, Thomas Abraham, Wafik S El-Deiry, Robert A Brodsky, Raymond J Hohl, Jeffrey J Pu
Previous studies have linked increased frequency of glycosylphosphatidylinositol-anchor protein (GPI-AP) deficiency with genomic instability and the risk of carcinogenesis. However, the underlying mechanism is still not clear. A randomForest analysis of the gene expression array data from 55 MDS patients (GSE4619) demonstrated a significant (p = 0.0007) correlation (Pearson r =-0.4068) between GPI-anchor biosynthesis gene expression and genomic instability, in which PIGN, a gene participating in GPI-AP biosynthesis, was ranked as the third most important in predicting risk of MDS progression...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28161389/detailed-expression-profile-of-all-six-glypicans-and-their-modifying-enzyme-notum-during-chick-embryogenesis-and-their-role-in-dorsal-ventral-patterning-of-the-neural-tube
#5
Kawakeb Saad, Anthony Otto, Susanne Theis, Niki Kennerley, Andrea Munsterberg, Graham Luke, Ketan Patel
Vertebrate development is orchestrated by secreted signalling molecules that regulate cell behaviour and cell fate decisions during early embryogenesis. The activity of key signalling molecules including members of Hedgehog, Bone Morphogenetic Proteins and Wnt families are regulated by Glypicans, a family of GPI linked polypeptides. Glypicans either promote or inhibit the action of signalling molecules and add a layer of complexity that needs to be understood in order to fully decipher the processes that regulate early vertebrate development...
April 20, 2017: Gene
https://www.readbyqxmd.com/read/28151558/whole-transcriptome-sequencing-identifies-increased-cxcr2-expression-in-pnh-granulocytes
#6
Kohei Hosokawa, Sachiko Kajigaya, Keyvan Keyvanfar, Wangmin Qiao, Yanling Xie, Angelique Biancotto, Danielle M Townsley, Xingmin Feng, Neal S Young
The aetiology of paroxysmal nocturnal haemoglobinuria (PNH) is a somatic mutation in the X-linked phosphatidylinositol glycan class A gene (PIGA), resulting in global deficiency of glycosyl phosphatidylinositol-anchored proteins (GPI-APs). This study applied RNA-sequencing to examine functional effects of the PIGA mutation in human granulocytes. CXCR2 expression was increased in GPI-AP(-) compared to GPI-AP(+) granulocytes. Macrophage migration inhibitory factor, a CXCR2 agonist, was significantly higher in plasma of PNH patients...
February 1, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28148964/cellular-prion-protein-is-present-in-mitochondria-of-healthy-mice
#7
Robert Faris, Roger A Moore, Anne Ward, Brent Race, David W Dorward, Jason R Hollister, Elizabeth R Fischer, Suzette A Priola
Cellular prion protein (PrP(C)) is a mammalian glycoprotein which is usually found anchored to the plasma membrane via a glycophosphatidylinositol (GPI) anchor. PrP(C) misfolds to a pathogenic isoform PrP(Sc), the causative agent of neurodegenerative prion diseases. The precise function of PrP(C) remains elusive but may depend upon its cellular localization. Here we show that PrP(C) is present in brain mitochondria from 6-12 week old wild-type and transgenic mice in the absence of disease. Mitochondrial PrP(C) was fully processed with mature N-linked glycans and did not require the GPI anchor for localization...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28062795/silac-based-proteomics-of-primary-human-kidney-cells-reveals-a-novel-link-between-male-sex-hormones-and-impaired-energy-metabolism-in-diabetic-kidney-disease
#8
Sergi Clotet, Maria Jose Soler, Marta Riera, Julio Pascual, Fei Fang, Joyce Zhou, Ihor Batruch, Stella K Vasiliou, Apostolos Dimitromanolakis, Clara Barrios, Eleftherios Diamandis, James Scholey, Ana Konvalinka
Male sex predisposes to many kidney diseases. Considering that androgens exert deleterious effects in a variety of cell types within kidney, we hypothesized that dihydrotestosterone (DHT) would alter the biology of the renal tubular cell by inducing changes in the proteome. We employed stable isotope labeling with amino acids (SILAC) in an indirect spike-in fashion to accurately quantify the proteome in DHT- and 17β-estradiol (EST)-treated human proximal tubular epithelial cells (PTEC). Of the 5043 quantified proteins, 76 were differentially regulated...
January 4, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/27937175/the-glycosylphosphatidylinositol-anchor-biosynthesis-genes-gpi12-gaa1-and-gpi8-are-essential-for-cell-wall-integrity-and-pathogenicity-of-the-maize-anthracnose-fungus-colletotrichum-graminicola
#9
Ely Oliveira-Garcia, Holger B Deising
Glycosylphosphatidylinositol (GPI) anchoring of proteins is one of the most common posttranslational modifications of proteins in eukaryotic cells and is important for associating proteins with the cell surface. In fungi, GPI-anchored proteins play essential roles in cross-linking of β-glucan cell-wall polymers and cell-wall rigidity. GPI-anchor synthesis is successively performed at the cytoplasmic and the luminal face of the ER membrane and involves approximately 25 proteins. While mutagenesis of auxiliary genes of this pathway suggested roles of GPI-anchored proteins in hyphal growth and virulence, essential genes of this pathway have not been characterized...
November 2016: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/27902399/truncation-of-the-enzootic-nasal-tumor-virus-envelope-protein-cytoplasmic-tail-increases-env-mediated-fusion-and-infectivity
#10
Scott R Walsh, Jondavid G de Jong, Jacob P van Vloten, María Carla Rosales Gerpe, Lisa A Santry, Sarah K Wootton
Enzootic nasal tumor virus (ENTV) and Jaagsiekte sheep retrovirus (JSRV) are highly related ovine betaretroviruses that induce nasal and lung tumours in small ruminants, respectively. While the ENTV and JSRV envelope (Env) glycoproteins mediate virus entry using the same cellular receptor, the glycosylphosphatidylinositol-linked protein hyaluronoglucosaminidase, ENTV Env pseudovirions mediate entry into cells from a much more restricted range of species than do JSRV Env pseudovirions. Unlike JSRV Env, ENTV Env does not induce cell fusion at pH 5...
January 2017: Journal of General Virology
https://www.readbyqxmd.com/read/27765999/hydrophobic-resorufamine-derivatives-potent-and-selective-red-fluorescent-probes-of-the-endoplasmic-reticulum-of-mammalian-cells
#11
Sahishna Phaniraj, Zhe Gao, Digamber Rane, Blake R Peterson
The endoplasmic reticulum (ER) of eukaryotic cells plays critical roles in the processing of secreted and transmembrane proteins. Defects in these functions are associated with a wide range of pathologies. To image this organelle, cells are often treated with fluorescent ER-Tracker dyes. Although these compounds are selective, existing red fluorescent probes of the ER are costly glibenclamide derivatives that inhibit ER-associated sulphonylurea receptors. To provide simpler and more cost-effective red fluorescent probes of the ER, we synthesized amino analogues of the fluorophore resorufin...
December 2016: Dyes and Pigments: An International Journal
https://www.readbyqxmd.com/read/27641538/n-glycosylation-enables-high-lateral-mobility-of-gpi-anchored-proteins-at-a-molecular-crowding-threshold
#12
Andreas J W Hartel, Marius Glogger, Nicola G Jones, Wasim Abuillan, Christopher Batram, Anne Hermann, Susanne F Fenz, Motomu Tanaka, Markus Engstler
The protein density in biological membranes can be extraordinarily high, but the impact of molecular crowding on the diffusion of membrane proteins has not been studied systematically in a natural system. The diversity of the membrane proteome of most cells may preclude systematic studies. African trypanosomes, however, feature a uniform surface coat that is dominated by a single type of variant surface glycoprotein (VSG). Here we study the density-dependence of the diffusion of different glycosylphosphatidylinositol-anchored VSG-types on living cells and in artificial membranes...
September 19, 2016: Nature Communications
https://www.readbyqxmd.com/read/27637482/monitoring-genotoxicity-in-patients-receiving-chemotherapy-for-cancer-application-of-the-pig-a-assay
#13
Katsuyoshi Horibata, Akiko Ukai, Shigeo Ishikawa, Ayako Sugano, Masamitsu Honma
The recently introduced Pig-a in vivo gene mutation assay measures endogeneous mutations of Pig-a (human, PIG-A), an X-linked gene that is conserved across species from rodents to humans. Flow cytometric analysis enables the enumeration of glycosylphosphatidylinositol (GPI) anchor-deficient erythrocytes, resulting from a mutation in Pig-a/PIG-A, in only a few microliters of peripheral blood. Pig-a/PIG-A mutations appear to function in a neutral manner, allowing evaluation of the accumulated genotoxic effects of repeated exposures...
September 15, 2016: Mutation Research. Genetic Toxicology and Environmental Mutagenesis
https://www.readbyqxmd.com/read/27542385/biomedical-applications-of-glycosylphosphatidylinositol-anchored-proteins
#14
Susanne Heider, John A Dangerfield, Christoph Metzner
Glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) use a unique posttranslational modification to link proteins to lipid bilayer membranes. The anchoring structure consists of both a lipid and carbohydrate portion and is highly conserved in eukaryotic organisms regarding its basic characteristics, yet highly variable in its molecular details. The strong membrane targeting property has made the anchors an interesting tool for biotechnological modification of lipid membrane-covered entities from cells through extracellular vesicles to enveloped virus particles...
October 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27523305/immunoglobulin-response-to-the-low-polymorphic-pf113-antigen-in-children-from-lastoursville-south-east-of-gabon
#15
Roméo Karl Imboumy-Limoukou, Sidney Maghendi-Nzondo, Charlene Lady Kouna, Lotfi Bounaadja, Sophie Mbang, Jean Claude Biteghe, Carole Eboumbou, Franck Prugnolle, Isabelle Florent, Jean-Bernard Lekana-Douki
Pf113 is a P. falciparum putatively GPI-anchored protein that has been so far localized at the surface of merozoites, suggesting it could interact with RBC surface during merozoite invasion. Previous studies conducted in Papua New Guinea and in Kenya have revealed that this protein is recognized by natural antibodies in individuals living in malaria-endemic areas and is associated with protective immunity in malaria, further supporting the potential of Pf113 for the development of anti-malaria vaccines. However, in Central Africa, no study on the immunogenicity of this protein has been conducted...
November 2016: Acta Tropica
https://www.readbyqxmd.com/read/27510749/anhydrobiosis-in-yeast-cell-wall-mannoproteins-are-important-for-yeast-saccharomyces-cerevisiae-resistance-to-dehydration
#16
Diana Borovikova, Renata Teparić, Vladimir Mrša, Alexander Rapoport
The state of anhydrobiosis is linked with the reversible delay of metabolism as a result of strong dehydration of cells, and is widely distributed in nature. A number of factors responsible for the maintenance of organisms' viability in these conditions have been revealed. This study was directed to understanding how changes in cell wall structure may influence the resistance of yeasts to dehydration-rehydration. Mutants lacking various cell wall mannoproteins were tested to address this issue. It was revealed that mutants lacking proteins belonging to two structurally and functionally unrelated groups (proteins non-covalently attached to the cell wall, and Pir proteins) possessed significantly lower cell resistance to dehydration-rehydration than the mother wild-type strain...
August 2016: Yeast
https://www.readbyqxmd.com/read/27504461/soluble-urokinase-receptors-in-focal-segmental-glomerulosclerosis-a-review-on-the-scientific-point-of-view
#17
REVIEW
Andreas Kronbichler, Moin A Saleem, Björn Meijers, Jae Il Shin
Focal segmental glomerulosclerosis (FSGS) is one of the primary glomerular disorders in both children and adults which can progress to end-stage renal failure. Although there are genetic and secondary causes, circulating factors have also been regarded as an important factor in the pathogenesis of FSGS, because about 40% of the patients with FSGS have recurrence after renal transplantation. Soluble urokinase-type plasminogen activator receptor (suPAR) is a soluble form of uPAR, which is a membrane-bound protein linked to GPI in various immunologically active cells, including podocytes...
2016: Journal of Immunology Research
https://www.readbyqxmd.com/read/27449504/cross-reactivity-between-annexin-a2-and-beta-2-glycoprotein-i-in-animal-models-of-antiphospholipid-syndrome
#18
R Weiss, A Bitton, L Nahary, M T Arango, I Benhar, M Blank, Y Shoenfeld, J Chapman
Antiphospholipid syndrome (APS) affects coagulation and the brain by autoimmune mechanisms. The major antigen in APS is beta-2-glycoprotein I (β2-GPI) is known to complex with annexin A2 (ANXA2), and antibodies to ANXA2 have been described in APS. We measured these antibodies in mice with experimental APS (eAPS) induced by immunization with β2-GPI. Sera of these mice reacted significantly with recombinant ANXA2 by enzyme-linked immunosorbent assay (ELISA) and the eAPS mice had significantly high levels of immunoglobulin G (IgG) in the brain by immunoblot assays compared to adjuvant immunized controls...
July 23, 2016: Immunologic Research
https://www.readbyqxmd.com/read/27426449/ceruloplasmin-is-regulated-by-copper-and-lactational-hormones-in-pmc42-la-mammary-epithelial-cell-culture-models
#19
David Freestone, Delphine Denoyer, Matthew Jakab, M Leigh Ackland, Michael A Cater, Agnes Michalczyk
Ceruloplasmin (Cp) is a multicopper ferroxidase that is considered to be an important source of copper in milk for normal neonatal development. We investigated the expression, subcellular localization and secretion of Cp in PMC42-LA cell culture models representative of resting, lactating and suckled human mammary epithelia. Both secreted Cp (sCp) and plasma membrane associated glycosylphosphatidylinositol-linked Cp (GPI-Cp) were expressed in PMC42-LA cells. In all three epithelial models (resting, lactating and suckled), the expression and secretion of copper-bound, ferroxidase active, Cp (holo-Cp) was dependent on media copper concentration...
September 1, 2016: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/27332042/mitochondrial-dysfunction-in-the-liver-and-antiphospholipid-antibody-production-precede-disease-onset-and-respond-to-rapamycin-in-lupus-prone-mice
#20
Zachary Oaks, Thomas Winans, Tiffany Caza, David Fernandez, Yuxin Liu, Steve K Landas, Katalin Banki, Andras Perl
OBJECTIVE: Antiphospholipid antibodies (aPL) constitute a diagnostic criterion of systemic lupus erythematosus (SLE), and aPL have been functionally linked to liver disease in patients with SLE. Since the mechanistic target of rapamycin (mTOR) is a regulator of oxidative stress, a pathophysiologic process that contributes to the development of aPL, this study was undertaken in a mouse model of SLE to examine the involvement of liver mitochondria in lupus pathogenesis. METHODS: Mitochondria were isolated from lupus-prone MRL/lpr, C57BL/6...
November 2016: Arthritis & Rheumatology
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