Database : MEDLINE
Search on : glycosylphosphatidylinositols [Words]
References found : 3657 [refine]
Displaying: 1 .. 10   in format [Detailed]

page 1 of 366 go to page                         

  1 / 3657 MEDLINE  
              next record last record
select
to print
Photocopy
Full text

[PMID]: 29374258
[Au] Autor:Hirata T; Mishra SK; Nakamura S; Saito K; Motooka D; Takada Y; Kanzawa N; Murakami Y; Maeda Y; Fujita M; Yamaguchi Y; Kinoshita T
[Ad] Address:Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, 565-0871, Japan.
[Ti] Title:Identification of a Golgi GPI-N-acetylgalactosamine transferase with tandem transmembrane regions in the catalytic domain.
[So] Source:Nat Commun;9(1):405, 2018 01 26.
[Is] ISSN:2041-1723
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Many eukaryotic proteins are anchored to the cell surface via the glycolipid glycosylphosphatidylinositol (GPI). Mammalian GPIs have a conserved core but exhibit diverse N-acetylgalactosamine (GalNAc) modifications, which are added via a yet unresolved process. Here we identify the Golgi-resident GPI-GalNAc transferase PGAP4 and show by mass spectrometry that PGAP4 knockout cells lose GPI-GalNAc structures. Furthermore, we demonstrate that PGAP4, in contrast to known Golgi glycosyltransferases, is not a single-pass membrane protein but contains three transmembrane domains, including a tandem transmembrane domain insertion into its glycosyltransferase-A fold as indicated by comparative modeling. Mutational analysis reveals a catalytic site, a DXD-like motif for UDP-GalNAc donor binding, and several residues potentially involved in acceptor binding. We suggest that a juxtamembrane region of PGAP4 accommodates various GPI-anchored proteins, presenting their acceptor residue toward the catalytic center. In summary, we present insights into the structure of PGAP4 and elucidate the initial step of GPI-GalNAc biosynthesis.
[Mh] MeSH terms primary: Acetylgalactosamine/chemistry
Glycosylphosphatidylinositols/chemistry
Golgi Apparatus/metabolism
N-Acetylgalactosaminyltransferases/chemistry
[Mh] MeSH terms secundary: Acetylgalactosamine/biosynthesis
Amino Acid Motifs
Animals
CHO Cells
Catalytic Domain
Cricetulus
Crystallography, X-Ray
Gene Expression
Genetic Vectors/chemistry
Genetic Vectors/metabolism
Glycosylphosphatidylinositols/metabolism
Golgi Apparatus/ultrastructure
Humans
Mice
Mice, Knockout
Models, Molecular
Mutation
N-Acetylgalactosaminyltransferases/genetics
N-Acetylgalactosaminyltransferases/metabolism
Protein Binding
Protein Conformation, alpha-Helical
Protein Conformation, beta-Strand
Protein Interaction Domains and Motifs
Structural Homology, Protein
Substrate Specificity
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Glycosylphosphatidylinositols); EC 2.4.1.- (N-Acetylgalactosaminyltransferases); EC 2.4.1.41 (polypeptide N-acetylgalactosaminyltransferase); KM15WK8O5T (Acetylgalactosamine)
[Em] Entry month:1802
[Cu] Class update date: 180227
[Lr] Last revision date:180227
[Js] Journal subset:IM
[Da] Date of entry for processing:180128
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02799-0

  2 / 3657 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 29409517
[Au] Autor:Abbasnia T; Asoodeh A; Habibi G; Haghparast A
[Ad] Address:Division of Biotechnology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, P.O. Box: 91775-1793, Mashhad, Iran.
[Ti] Title:Isolation and purification of glycosylphosphatidylinositols (GPIs) in the schizont stage of Theileria annulata and determination of antibody response to GPI anchors in vaccinated and infected animals.
[So] Source:Parasit Vectors;11(1):82, 2018 Feb 06.
[Is] ISSN:1756-3305
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract: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. GPIs are particularly abundant in protozoan parasites, where they are found as free glycolipids or attached to proteins in the plasma membrane. RESULTS: In this study we first isolated and purified schizonts of Theileria annulata from infected leukocytes in Theileria annulata vaccine cell line (S15) by aerolysin-percoll technique. Then, the free GPIs of schizont stage and isolated GPI from cell membrane glycoproteins were purified by high performance liquid chromatography (HPLC) and confirmed by gas chromatography-mass spectrometry (GC-MS). Furthermore, enzyme linked immunosorbent assay (ELISA) on the serum samples obtained from naturally infected, as well as Theileria annulata-vaccinated animals, confirmed a significant (P < 0.01) high level of anti-GPI antibody in their serum. CONCLUSIONS: The results presented in this study show, to our knowledge for the first time, the isolation of GPI from the schizont stage of Theileria annulata and demonstrate the presence of anti-GPI antibody in the serum of naturally infected as well as vaccinated animals. This finding is likely to be valuable in studies aimed at the evaluation of chemically structures of GPIs in the schizont stage of Theileria annulata and also for pathogenicity and immunogenicity studies with the aim to develop GPI-based therapies or vaccines.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180216
[Lr] Last revision date:180216
[St] Status:In-Data-Review
[do] DOI:10.1186/s13071-018-2651-9

  3 / 3657 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 28459879
[Au] Autor:Tiengwe C; Bush PJ; Bangs JD
[Ad] Address:Department of Microbiology & Immunology, School of Medicine and Biomedical Sciences, University at Buffalo (SUNY), Buffalo, New York, United States of America.
[Ti] Title:Controlling transferrin receptor trafficking with GPI-valence in bloodstream stage African trypanosomes.
[So] Source:PLoS Pathog;13(5):e1006366, 2017 May.
[Is] ISSN:1553-7374
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Bloodstream-form African trypanosomes encode two structurally related glycosylphosphatidylinositol (GPI)-anchored proteins that are critical virulence factors, variant surface glycoprotein (VSG) for antigenic variation and transferrin receptor (TfR) for iron acquisition. Both are transcribed from the active telomeric expression site. VSG is a GPI2 homodimer; TfR is a GPI1 heterodimer of GPI-anchored ESAG6 and ESAG7. GPI-valence correlates with secretory progression and fate in bloodstream trypanosomes: VSG (GPI2) is a surface protein; truncated VSG (GPI0) is degraded in the lysosome; and native TfR (GPI1) localizes in the flagellar pocket. Tf:Fe starvation results in up-regulation and redistribution of TfR to the plasma membrane suggesting a saturable mechanism for flagellar pocket retention. However, because such surface TfR is non-functional for ligand binding we proposed that it represents GPI2 ESAG6 homodimers that are unable to bind transferrin-thereby mimicking native VSG. We now exploit a novel RNAi system for simultaneous lethal silencing of all native TfR subunits and exclusive in-situ expression of RNAi-resistant TfR variants with valences of GPI0-2. Our results conform to the valence model: GPI0 ESAG7 homodimers traffick to the lysosome and GPI2 ESAG6 homodimers to the cell surface. However, when expressed alone ESAG6 is up-regulated ~7-fold, leaving the issue of saturable retention in the flagellar pocket in question. Therefore, we created an RNAi-resistant GPI2 TfR heterodimer by fusing the C-terminal domain of ESAG6 to ESAG7. Co-expression with ESAG6 generates a functional heterodimeric GPI2 TfR that restores Tf uptake and cell viability, and localizes to the cell surface, without overexpression. These results resolve the longstanding issue of TfR trafficking under over-expression and confirm GPI valence as a critical determinant of intracellular sorting in trypanosomes.
[Mh] MeSH terms primary: Glycosylphosphatidylinositols/metabolism
Protein Transport
Receptors, Transferrin/metabolism
Trypanosoma brucei brucei/physiology
Trypanosomiasis, African/parasitology
Variant Surface Glycoproteins, Trypanosoma/metabolism
[Mh] MeSH terms secundary: Amino Acid Sequence
Animals
Base Sequence
Cell Line
Cell Membrane/metabolism
Dimerization
Glycosylphosphatidylinositols/genetics
Humans
Lysosomes/metabolism
RNA Interference
Receptors, Transferrin/genetics
Sequence Alignment
Trypanosoma brucei brucei/genetics
Trypanosoma brucei brucei/ultrastructure
Up-Regulation
Variant Surface Glycoproteins, Trypanosoma/genetics
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Glycosylphosphatidylinositols); 0 (Receptors, Transferrin); 0 (Variant Surface Glycoproteins, Trypanosoma)
[Em] Entry month:1710
[Cu] Class update date: 171212
[Lr] Last revision date:171212
[Js] Journal subset:IM
[Da] Date of entry for processing:170502
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006366

  4 / 3657 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 29100095
[Au] Autor:Nguyen TTM; Murakami Y; Sheridan E; Ehresmann S; Rousseau J; St-Denis A; Chai G; Ajeawung NF; Fairbrother L; Reimschisel T; Bateman A; Berry-Kravis E; Xia F; Tardif J; Parry DA; Logan CV; Diggle C; Bennett CP; Hattingh L; Rosenfeld JA; Perry MS; Parker MJ; Le Deist F; Zaki MS; Ignatius E; Isohanni P; Lönnqvist T; Carroll CJ; Johnson CA; Gleeson JG; Kinoshita T; Campeau PM
[Ad] Address:Centre Hospitalier Universitaire Sainte Justine Research Center, University of Montreal, Montreal, QC H3T1C5, Canada.
[Ti] Title:Mutations in GPAA1, Encoding a GPI Transamidase Complex Protein, Cause Developmental Delay, Epilepsy, Cerebellar Atrophy, and Osteopenia.
[So] Source:Am J Hum Genet;101(5):856-865, 2017 Nov 02.
[Is] ISSN:1537-6605
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Approximately one in every 200 mammalian proteins is anchored to the cell membrane through a glycosylphosphatidylinositol (GPI) anchor. These proteins play important roles notably in neurological development and function. To date, more than 20 genes have been implicated in the biogenesis of GPI-anchored proteins. GPAA1 (glycosylphosphatidylinositol anchor attachment 1) is an essential component of the transamidase complex along with PIGK, PIGS, PIGT, and PIGU (phosphatidylinositol-glycan biosynthesis classes K, S, T, and U, respectively). This complex orchestrates the attachment of the GPI anchor to the C terminus of precursor proteins in the endoplasmic reticulum. Here, we report bi-allelic mutations in GPAA1 in ten individuals from five families. Using whole-exome sequencing, we identified two frameshift mutations (c.981_993del [p.Gln327Hisfs 102] and c.920delG [p.Gly307Alafs 11]), one intronic splicing mutation (c.1164+5C>T), and six missense mutations (c.152C>T [p.Ser51Leu], c.160_161delinsAA [p.Ala54Asn], c.527G>C [p.Trp176Ser], c.869T>C [p.Leu290Pro], c.872T>C [p.Leu291Pro], and c.1165G>C [p.Ala389Pro]). Most individuals presented with global developmental delay, hypotonia, early-onset seizures, cerebellar atrophy, and osteopenia. The splicing mutation was found to decrease GPAA1 mRNA. Moreover, flow-cytometry analysis of five available individual samples showed that several GPI-anchored proteins had decreased cell-surface abundance in leukocytes (FLAER, CD16, and CD59) or fibroblasts (CD73 and CD109). Transduction of fibroblasts with a lentivirus encoding the wild-type protein partially rescued the deficiency of GPI-anchored proteins. These findings highlight the role of the transamidase complex in the development and function of the cerebellum and the skeletal system.
[Mh] MeSH terms primary: Acyltransferases/genetics
Atrophy/genetics
Bone Diseases, Metabolic/genetics
Developmental Disabilities/genetics
Epilepsy/genetics
Membrane Glycoproteins/genetics
Mutation/genetics
[Mh] MeSH terms secundary: Adolescent
Adult
Alleles
Cerebellum/pathology
Child
Child, Preschool
Exome/genetics
Female
Fibroblasts/pathology
Glycosylphosphatidylinositols/genetics
Humans
Male
Muscle Hypotonia/genetics
Pedigree
RNA, Messenger/genetics
Seizures/genetics
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (GPAA1 protein, human); 0 (Glycosylphosphatidylinositols); 0 (Membrane Glycoproteins); 0 (RNA, Messenger); EC 2.3.- (Acyltransferases); EC 2.3.2.- (COOH-terminal signal transamidase)
[Em] Entry month:1711
[Cu] Class update date: 171118
[Lr] Last revision date:171118
[Js] Journal subset:IM
[Da] Date of entry for processing:171104
[St] Status:MEDLINE

  5 / 3657 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 28784611
[Au] Autor:Snider CE; Willet AH; Chen JS; Arpag G; Zanic M; Gould KL
[Ad] Address:Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN.
[Ti] Title:Phosphoinositide-mediated ring anchoring resists perpendicular forces to promote medial cytokinesis.
[So] Source:J Cell Biol;216(10):3041-3050, 2017 Oct 02.
[Is] ISSN:1540-8140
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Many eukaryotic cells divide by assembling and constricting an actin- and myosin-based contractile ring (CR) that is physically linked to the plasma membrane (PM). In this study, we report that cells lacking , which encodes a conserved PM scaffold for the phosphatidylinositol-4 kinase Stt4, build CRs that can slide away from the cell middle during anaphase in a myosin V-dependent manner. The Efr3-dependent CR-anchoring mechanism is distinct from previously reported pathways dependent on the Fes/CIP4 homology Bin-Amphiphysin-Rvs167 (F-BAR) protein Cdc15 and paxillin Pxl1. In , the concentrations of several membrane-binding proteins were reduced in the CR and/or on the PM. Our results suggest that proper PM lipid composition is important to stabilize the central position of the CR and resist myosin V-based forces to promote the fidelity of cell division.
[Mh] MeSH terms primary: Cytokinesis/physiology
Glycosylphosphatidylinositols/metabolism
Schizosaccharomyces/metabolism
[Mh] MeSH terms secundary: 1-Phosphatidylinositol 4-Kinase/genetics
1-Phosphatidylinositol 4-Kinase/metabolism
Cell Cycle Proteins/genetics
Cell Cycle Proteins/metabolism
GTP-Binding Proteins/genetics
GTP-Binding Proteins/metabolism
Glycosylphosphatidylinositols/genetics
Myosin Type V/genetics
Myosin Type V/metabolism
Schizosaccharomyces/genetics
Schizosaccharomyces pombe Proteins/genetics
Schizosaccharomyces pombe Proteins/metabolism
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (CDC15 protein); 0 (Cell Cycle Proteins); 0 (Glycosylphosphatidylinositols); 0 (Schizosaccharomyces pombe Proteins); EC 2.7.1.67 (1-Phosphatidylinositol 4-Kinase); EC 3.6.1.- (GTP-Binding Proteins); EC 3.6.1.- (Myosin Type V)
[Em] Entry month:1710
[Cu] Class update date: 171007
[Lr] Last revision date:171007
[Js] Journal subset:IM
[Da] Date of entry for processing:170809
[St] Status:MEDLINE
[do] DOI:10.1083/jcb.201705070

  6 / 3657 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 28729427
[Au] Autor:Nolan W; McHale-Owen H; Bate C
[Ad] Address:Department of Pathology and Pathogen Biology, Royal Veterinary College, Hawkshead Lane, North Mymms, Herts AL9 7TA, U.K.
[Ti] Title:Sialylated glycosylphosphatidylinositols suppress the production of toxic amyloid-ß oligomers.
[So] Source:Biochem J;474(17):3045-3058, 2017 Aug 22.
[Is] ISSN:1470-8728
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:The production of amyloid-ß (Aß) is a key factor driving pathogenesis in Alzheimer's disease (AD). Increasing concentrations of soluble Aß oligomers within the brain lead to synapse degeneration and the progressive dementia characteristic of AD. Since Aß exists in both disease-relevant (toxic) and non-toxic forms, the factors that affected the release of toxic Aß were studied in a cell model. 7PA2 cells expressing the human amyloid precursor protein released Aß oligomers that caused synapse damage when incubated with cultured neurones. These Aß oligomers had similar potency to soluble Aß oligomers derived from the brains of Alzheimer's patients. Although the conditioned media from 7PA2 cells treated with the cellular prion protein (PrP ) contained Aß, it did not cause synapse damage. The loss of toxicity was associated with a reduction in Aß oligomers and an increase in Aß monomers. The suppression of toxic Aß release was dependent on the glycosylphosphatidylinositol (GPI) anchor attached to PrP , and treatment of cells with specific GPIs alone reduced the production of toxic Aß. The efficacy of GPIs was structure-dependent and the presence of sialic acid was critical. The conditioned medium from GPI-treated cells protected neurones against Aß oligomer-induced synapse damage; neuroprotection was mediated by Aß monomers. These studies support the hypothesis that the ratio of Aß monomers to Aß oligomers is a critical factor that regulates synapse damage.
[Mh] MeSH terms primary: Alzheimer Disease/metabolism
Amyloid beta-Protein Precursor/metabolism
Glycosylphosphatidylinositols/metabolism
Neurons/metabolism
Oligosaccharides/metabolism
Synapses/metabolism
[Mh] MeSH terms secundary: Alzheimer Disease/genetics
Alzheimer Disease/pathology
Amyloid beta-Protein Precursor/genetics
Animals
CHO Cells
Cricetinae
Cricetulus
Glycosylphosphatidylinositols/genetics
Humans
Mice
Neurons/pathology
Oligosaccharides/genetics
PrPC Proteins/genetics
PrPC Proteins/metabolism
Synapses/genetics
Synapses/pathology
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 ((6-O-aminoethylphosphonato-mannopyranosyl)-(1-2)-mannopyranosyl-(1-6)-mannopyranosyl-(1-4)-(2-amino-2-deoxyglucopyranosyl)-(1-6)-1-O-(1,2-di-O-octadecanoyl-sn-glyceryl-phosphonato)-myo-inositol); 0 (APP protein, human); 0 (Amyloid beta-Protein Precursor); 0 (Glycosylphosphatidylinositols); 0 (Oligosaccharides); 0 (PrPC Proteins)
[Em] Entry month:1708
[Cu] Class update date: 170831
[Lr] Last revision date:170831
[Js] Journal subset:IM
[Da] Date of entry for processing:170722
[St] Status:MEDLINE
[do] DOI:10.1042/BCJ20170239

  7 / 3657 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 28714084
[Au] Autor:Ji Z; LeBaron MJ
[Ad] Address:Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, Michigan, 48674.
[Ti] Title:Applying the erythrocyte Pig-a assay concept to rat epididymal sperm for germ cell mutagenicity evaluation.
[So] Source:Environ Mol Mutagen;58(7):485-493, 2017 Aug.
[Is] ISSN:1098-2280
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The Pig-a assay, a recently developed in vivo somatic gene mutation assay, is based on the identification of mutant erythrocytes that have an altered repertoire of glycosylphosphatidylinositol (GPI)-anchored cell surface markers. We hypothesized that the erythrocyte Pig-a assay concept could be applied to rat cauda epididymal spermatozoa (sperm) for germ cell mutagenicity evaluation. We used GPI-anchored CD59 as the Pig-a mutation marker and examined the frequency of CD59-negative sperm using flow cytometry. A reconstruction experiment that spiked un-labeled sperm (mutant-mimic) into labeled sperm at specific ratios yielded good agreement between the detected and expected frequencies of mutant-mimic sperm, demonstrating the analytical ability for CD59-negative sperm detection. Furthermore, this methodology was assessed in F344/DuCrl rats administered N-ethyl-N-nitrosourea (ENU), a prototypical mutagen, or clofibrate, a lipid-lowering drug. Rats treated with 1, 10, or 20 mg/kg body weight/day (mkd) ENU via daily oral garage for five consecutive days showed a dose-dependent increase in the frequency of CD59-negative sperm on study day 63 (i.e., 58 days after the last ENU dose). This ENU dosing regimen also increased the frequency of CD59-negative erythrocytes. In rats treated with 300 mkd clofibrate via daily oral garage for consecutive 28 days, no treatment-related changes were detected in the frequency of CD59-negative sperm on study day 85 (i.e., 57 days after the last dose) or in the frequency of CD59-negative erythrocytes on study day 29. In conclusion, these data suggest that the epidiymal sperm Pig-a assay in rats is a promising method for evaluating germ cell mutagenicity. Environ. Mol. Mutagen. 58:485-493, 2017. © 2017 Wiley Periodicals, Inc.
[Mh] MeSH terms primary: Epididymis
Membrane Proteins/genetics
Mutagenicity Tests/methods
Mutagens/toxicity
Spermatozoa/drug effects
[Mh] MeSH terms secundary: Animals
CD59 Antigens/genetics
Clofibrate/toxicity
Erythrocytes/drug effects
Erythrocytes/metabolism
Erythrocytes/pathology
Ethylnitrosourea/toxicity
Flow Cytometry
Glycosylphosphatidylinositols/biosynthesis
Male
Rats, Inbred F344
Spermatozoa/metabolism
Spermatozoa/pathology
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (CD59 Antigens); 0 (Glycosylphosphatidylinositols); 0 (Membrane Proteins); 0 (Mutagens); 0 (phosphatidylinositol glycan-class A protein); HPN91K7FU3 (Clofibrate); P8M1T4190R (Ethylnitrosourea)
[Em] Entry month:1708
[Cu] Class update date: 171116
[Lr] Last revision date:171116
[Js] Journal subset:IM
[Da] Date of entry for processing:170718
[St] Status:MEDLINE
[do] DOI:10.1002/em.22109

  8 / 3657 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 28529974
[Au] Autor:Chasen NM; Asady B; Lemgruber L; Vommaro RC; Kissinger JC; Coppens I; Moreno SNJ
[Ad] Address:Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia, USA.
[Ti] Title:A Glycosylphosphatidylinositol-Anchored Carbonic Anhydrase-Related Protein of Is Important for Rhoptry Biogenesis and Virulence.
[So] Source:mSphere;2(3), 2017 May-Jun.
[Is] ISSN:2379-5042
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Carbonic anhydrase-related proteins (CARPs) have previously been described as catalytically inactive proteins closely related to α-carbonic anhydrases (α-CAs). These CARPs are found in animals (both vertebrates and invertebrates) and viruses as either independent proteins or domains of other proteins. We report here the identification of a new CARP (TgCA_RP) in the unicellular organism that is related to the recently described η-class CA found in . TgCA_RP is posttranslationally modified at its C terminus with a glycosylphosphatidylinositol anchor that is important for its localization in intracellular tachyzoites. The protein localizes throughout the rhoptry bulbs of mature tachyzoites and to the outer membrane of nascent rhoptries in dividing tachyzoites, as demonstrated by immunofluorescence and immunoelectron microscopy using specific antibodies. mutant tachyzoites lacking display a growth and invasion phenotype and have atypical rhoptry morphology. The mutants also exhibit reduced virulence in a mouse model. Our results show that TgCA_RP plays an important role in the biogenesis of rhoptries. is an intracellular pathogen that infects humans and animals. The pathogenesis of is linked to its lytic cycle, which starts when tachyzoites invade host cells and secrete proteins from specialized organelles. Once inside the host cell, the parasite creates a parasitophorous vacuole (PV) where it divides. Rhoptries are specialized secretory organelles that contain proteins, many of which are secreted during invasion. These proteins have important roles not only during the initial interaction between parasite and host but also in the formation of the PV and in the modification of the host cell. We report here the identification of a new carbonic anhydrase-related protein (TgCA_RP), which localizes to rhoptries of mature tachyzoites. TgCA_RP is important for the morphology of rhoptries and for invasion and growth of parasites. TgCA_RP is also critical for parasite virulence. We propose that TgCA_RP plays a role in the biogenesis of rhoptries.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1705
[Cu] Class update date: 171110
[Lr] Last revision date:171110
[St] Status:PubMed-not-MEDLINE

  9 / 3657 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 28334793
[Au] Autor:Johnstone DL; Nguyen TT; Murakami Y; Kernohan KD; Tétreault M; Goldsmith C; Doja A; Wagner JD; Huang L; Hartley T; St-Denis A; le Deist F; Majewski J; Bulman DE; Kinoshita T; Dyment DA; Boycott KM; Campeau PM; Care4Rare Canada Consortium
[Ad] Address:Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario K1H8L1, Canada.
[Ti] Title:Compound heterozygous mutations in the gene PIGP are associated with early infantile epileptic encephalopathy.
[So] Source:Hum Mol Genet;26(9):1706-1715, 2017 May 01.
[Is] ISSN:1460-2083
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:There are over 150 known human proteins which are tethered to the cell surface via glycosylphosphatidylinositol (GPI) anchors. These proteins play a variety of important roles in development, and particularly in neurogenesis. Not surprisingly, mutations in the GPI anchor biosynthesis and remodeling pathway cause a number of developmental disorders. This group of conditions has been termed inherited GPI deficiencies (IGDs), a subgroup of congenital disorders of glycosylation; they present with variable phenotypes, often including seizures, hypotonia and intellectual disability. Here, we report two siblings with compound heterozygous variants in the gene phosphatidylinositol glycan anchor biosynthesis, class P (PIGP) (NM_153681.2: c.74T > C;p.Met25Thr and c.456delA;p.Glu153AsnFs*34). PIGP encodes a subunit of the enzyme that catalyzes the first step of GPI anchor biosynthesis. Both children presented with early-onset refractory seizures, hypotonia, and profound global developmental delay, reminiscent of other IGD phenotypes. Functional studies with patient cells showed reduced PIGP mRNA levels, and an associated reduction of GPI-anchored cell surface proteins, which was rescued by exogenous expression of wild-type PIGP. This work associates mutations in the PIGP gene with a novel autosomal recessive IGD, and expands our knowledge of the role of PIG genes in human development.
[Mh] MeSH terms primary: Hexosyltransferases/genetics
Membrane Proteins/genetics
Spasms, Infantile/genetics
[Mh] MeSH terms secundary: Abnormalities, Multiple/genetics
Adult
Cell Line
Child
Developmental Disabilities/genetics
Glycosylphosphatidylinositols/deficiency
Glycosylphosphatidylinositols/genetics
Glycosylphosphatidylinositols/metabolism
Hemoglobinuria, Paroxysmal/genetics
Hexosyltransferases/metabolism
Humans
Intellectual Disability/genetics
Membrane Proteins/metabolism
Muscle Hypotonia/genetics
Mutation
Pedigree
Seizures/genetics
Spasms, Infantile/metabolism
[Pt] Publication type:CASE REPORTS; JOURNAL ARTICLE
[Nm] Name of substance:0 (Glycosylphosphatidylinositols); 0 (Membrane Proteins); EC 2.4.1.- (Hexosyltransferases); EC 2.4.1.198 (PIGP protein, human)
[Em] Entry month:1710
[Cu] Class update date: 171017
[Lr] Last revision date:171017
[Js] Journal subset:IM
[Da] Date of entry for processing:170324
[St] Status:MEDLINE
[do] DOI:10.1093/hmg/ddx077

  10 / 3657 MEDLINE  
              first record previous record
select
to print
Photocopy
Full text

[PMID]: 28331092
[Au] Autor:Realegeno S; Puschnik AS; Kumar A; Goldsmith C; Burgado J; Sambhara S; Olson VA; Carroll D; Damon I; Hirata T; Kinoshita T; Carette JE; Satheshkumar PS
[Ad] Address:Poxvirus and Rabies Branch, Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
[Ti] Title:Monkeypox Virus Host Factor Screen Using Haploid Cells Identifies Essential Role of GARP Complex in Extracellular Virus Formation.
[So] Source:J Virol;91(11), 2017 Jun 01.
[Is] ISSN:1098-5514
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:(MPXV) is a human pathogen that is a member of the genus, which includes and (the causative agent of smallpox). Human monkeypox is considered an emerging zoonotic infectious disease. To identify host factors required for MPXV infection, we performed a genome-wide insertional mutagenesis screen in human haploid cells. The screen revealed several candidate genes, including those involved in Golgi trafficking, glycosaminoglycan biosynthesis, and glycosylphosphatidylinositol (GPI)-anchor biosynthesis. We validated the role of a set of vacuolar protein sorting (VPS) genes during infection, VPS51 to VPS54 (VPS51-54), which comprise the Golgi-associated retrograde protein (GARP) complex. The GARP complex is a tethering complex involved in retrograde transport of endosomes to the -Golgi apparatus. Our data demonstrate that VPS52 and VPS54 were dispensable for mature virion (MV) production but were required for extracellular virus (EV) formation. For comparison, a known antiviral compound, ST-246, was used in our experiments, demonstrating that EV titers in VPS52 and VPS54 knockout (KO) cells were comparable to levels exhibited by ST-246-treated wild-type cells. Confocal microscopy was used to examine actin tail formation, one of the viral egress mechanisms for cell-to-cell dissemination, and revealed an absence of actin tails in VPS52KO- or VPS54KO-infected cells. Further evaluation of these cells by electron microscopy demonstrated a decrease in levels of wrapped viruses (WVs) compared to those seen with the wild-type control. Collectively, our data demonstrate the role of GARP complex genes in double-membrane wrapping of MVs necessary for EV formation, implicating the host endosomal trafficking pathway in orthopoxvirus infection. Human monkeypox is an emerging zoonotic infectious disease caused by (MPXV). Of the two MPXV clades, the Congo Basin strain is associated with severe disease, increased mortality, and increased human-to-human transmission relative to the West African strain. Monkeypox is endemic in regions of western and central Africa but was introduced into the United States in 2003 from the importation of infected animals. The threat of MPXV and other orthopoxviruses is increasing due to the absence of routine smallpox vaccination leading to a higher proportion of naive populations. In this study, we have identified and validated candidate genes that are required for MPXV infection, specifically, those associated with the Golgi-associated retrograde protein (GARP) complex. Identifying host targets required for infection that prevents extracellular virus formation such as the GARP complex or the retrograde pathway can provide a potential target for antiviral therapy.
[Mh] MeSH terms primary: Endosomes/metabolism
Host-Pathogen Interactions
Membrane Proteins/genetics
Monkeypox virus/physiology
Vesicular Transport Proteins/metabolism
[Mh] MeSH terms secundary: Actins/drug effects
Actins/metabolism
Animals
Benzamides/pharmacology
Biological Transport
Cell Line
Genome, Human
Glycosaminoglycans/biosynthesis
Glycosaminoglycans/genetics
Glycosylphosphatidylinositols/biosynthesis
Golgi Apparatus/genetics
Golgi Apparatus/metabolism
Haploidy
Humans
Isoindoles/pharmacology
Membrane Proteins/metabolism
Monkeypox/virology
Mutagenesis, Insertional
Vesicular Transport Proteins/genetics
Viral Load
Virus Replication
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Actins); 0 (Benzamides); 0 (Glycosaminoglycans); 0 (Glycosylphosphatidylinositols); 0 (Isoindoles); 0 (LRRC32 protein, human); 0 (Membrane Proteins); 0 (ST-246); 0 (VPS53 protein, human); 0 (Vesicular Transport Proteins)
[Em] Entry month:1707
[Cu] Class update date: 171112
[Lr] Last revision date:171112
[Js] Journal subset:IM
[Da] Date of entry for processing:170324
[St] Status:MEDLINE


page 1 of 366 go to page                         
   


Refine the search
  Database : MEDLINE Advanced form   

    Search in field  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/PAHO/WHO - Latin American and Caribbean Center on Health Sciences Information