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Alan F Cowman - One of the best experts on this subject based on the ideXlab platform.
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a novel erythrocyte Binding antigen 175 paralogue from plasmodium falciparum defines a new trypsin resistant receptor on human erythrocytes
Journal of Biological Chemistry, 2003Co-Authors: Timwolf Gilberger, Manoj T Duraisingh, Jennifer K Thompson, Tony Triglia, Robert T Good, Alan F CowmanAbstract:ABstract The recognition and invasion of human erythrocytes By the most lethal malaria parasite Plasmodium falciparum is dependent on multiple ligand-receptor interactions. MemBers of the erythrocyte Binding-like (eBl) family, including the erythrocyte Binding antigen-175 (EBA-175), are responsiBle for high affinity Binding to glycoproteins on the surface of the erythrocyte. Here we descriBe a paralogue of EBA-175 and show that this protein (EBA-181/JESEBL) Binds in a sialic acid-dependent manner to erythrocytes. EBA-181 is expressed at the same time as EBA-175 and co-localizes with this protein in the microneme organelles of asexual stage parasites. The receptor Binding specificity of EBA-181 to erythrocytes differs from other memBers of the eBl family and is trypsin-resistant and chymotrypsin-sensitive. Furthermore, using <B>GlycophorinB> B-deficient erythrocytes we show that Binding of EBA-181 is not dependent on this sialoglycoprotein. The level of expression of EBA-181 differs among parasite lines, and the importance of this ligand for invasion appears to Be strain-dependent as the EBA-181 gene can Be disrupted in W2mef parasites, without affecting the invasion phenotype, But cannot Be targeted in 3D7 parasites.
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a novel erythrocyte Binding antigen 175 paralogue fromplasmodium falciparum defines a new trypsin resistant receptor on human erythrocytes
Journal of Biological Chemistry, 2003Co-Authors: Timwolf Gilberger, Manoj T Duraisingh, Jennifer K Thompson, Tony Triglia, Robert T Good, Alan F CowmanAbstract:The recognition and invasion of human erythrocytes By the most lethal malaria parasite Plasmodium falciparum is dependent on multiple ligand-receptor interactions. MemBers of the erythrocyte Binding-like (eBl) family, including the erythrocyte Binding antigen-175 (EBA-175), are responsiBle for high affinity Binding to glycoproteins on the surface of the erythrocyte. Here we descriBe a paralogue of EBA-175 and show that this protein (EBA-181/JESEBL) Binds in a sialic acid-dependent manner to erythrocytes. EBA-181 is expressed at the same time as EBA-175 and co-localizes with this protein in the microneme organelles of asexual stage parasites. The receptor Binding specificity of EBA-181 to erythrocytes differs from other memBers of the eBl family and is trypsin-resistant and chymotrypsin-sensitive. Furthermore, using <B>GlycophorinB> B-deficient erythrocytes we show that Binding of EBA-181 is not dependent on this sialoglycoprotein. The level of expression of EBA-181 differs among parasite lines, and the importance of this ligand for invasion appears to Be strain-dependent as the EBA-181 gene can Be disrupted in W2mef parasites, without affecting the invasion phenotype, But cannot Be targeted in 3D7 parasites.
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A novel ligand from Plasmodium falciparum that Binds to a sialic acid-containing receptor on the surface of human erythrocytes.
Molecular microbiology, 2001Co-Authors: Jennifer K Thompson, Tony Triglia, Michael B. Reed, Alan F CowmanAbstract:Summary Invasion of the merozoite form of Plasmodium falciparum into human erythrocytes involves multiple receptor‐ligand interactions. The EBA175 protein of P. falciparum has Been shown to Be the ligand that Binds to a sialic acid-dependent site on <B>GlycophorinB> A. We have identified a novel P. falciparum ligand, termed erythrocyte-Binding antigen 140 (EBA140), that shares structural features and homology with EBA175. SuBcellular localization of EBA140 suggests that it is located in the micronemes, the same localization as EBA175. EBA140 Binds to a sialic acid-dependent receptor on the surface of human erythrocytes. Binding of EBA140 to this erythrocyte receptor is sensitive to neuraminidase and resistant to trypsin, proteinase K and pronase. The proteaseresistant properties of the erythrocyte receptor suggests that it is not <B>GlycophorinB> A or C. Additionally, analysis of mutant erythrocytes from humans has shown that EBA140 does not Bind <B>GlycophorinB> B. Interestingly, we have identified a parasite line that lacks the eBa140 gene, suggesting that this protein is not essential for in vitro invasion. These results suggest that EBA140 may Be involved in merozoite invasion using a sialic acid-dependent receptor on human erythrocytes.
Louis H. Miller - One of the best experts on this subject based on the ideXlab platform.
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<B>GlycophorinB> B is the erythrocyte receptor of Plasmodium falciparum erythrocyte-Binding ligand, EBL-1
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: D. C. Ghislaine Mayer, Joann Cofie, Lubin Jiang, Daniel L. Hartl, Erin Tracy, Juraj Kabat, Laurence H. Mendoza, Louis H. MillerAbstract:In the war against Plasmodium, humans have evolved to eliminate or modify proteins on the erythrocyte surface that serve as receptors for parasite invasion, such as the Duffy Blood group, a receptor for Plasmodium vivax, and the GerBich-negative modification of <B>GlycophorinB> C for Plasmodium falciparum. In turn, the parasite counters with expansion and diversification of ligand families. The high degree of polymorphism in <B>GlycophorinB> B found in malaria-endemic regions suggests that it also may Be a receptor for Plasmodium, But, to date, none has Been identified. We provide evidence from erythrocyte-Binding that <B>GlycophorinB> B is a receptor for the P. falciparum protein EBL-1, a memBer of the Duffy-Binding-like erythrocyte-Binding protein (DBL-EBP) receptor family. The erythrocyte-Binding domain, region 2 of EBL-1, expressed on CHO-K1 cells, Bound <B>GlycophorinB> B+ But not <B>GlycophorinB> B-null erythrocytes. In addition, <B>GlycophorinB> B+ But not <B>GlycophorinB> B-null erythrocytes adsorBed native EBL-1 from the P. falciparum culture supernatants. Interestingly, the Efe pygmies of the Ituri forest in the Democratic RepuBlic of the Congo have the highest gene frequency of <B>GlycophorinB> B-null in the world, raising the possiBility that the DBL-EBP family may have expanded in response to the high frequency of <B>GlycophorinB> B-null in the population.
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Plasmodium falciparum is aBle to invade erythrocytes through a trypsin-resistant pathway independent of <B>GlycophorinB> B
Infection and immunity, 2003Co-Authors: Deepak Gaur, John W Barnwell, Marion E. Reid, Jill R. Storry, Louis H. MillerAbstract:Plasmodium falciparum invades erythrocytes through multiple ligand-receptor interactions, with redundancies in each pathway. One such alternate pathway is the trypsin-resistant pathway that enaBles P. falciparum to invade trypsin-treated erythrocytes. Previous studies have shown that this trypsin-resistant pathway is dependent on <B>GlycophorinB> B, as P. falciparum strains invade trypsin-digested <B>GlycophorinB> B-deficient erythrocytes at a highly reduced efficiency. Furthermore, in a recent study, the P. falciparum 7G8 strain did not invade <B>GlycophorinB> B-deficient erythrocytes, a finding that was not confirmed in the present study. To analyze the degree of dependence on <B>GlycophorinB> B for invasion By P. falciparum through the trypsin-resistant pathway, we have studied the invasion phenotypes of five parasite strains, 3D7, HB3, Dd2, 7G8, and Indochina I, on trypsin-treated normal and <B>GlycophorinB> B-deficient erythrocytes. Invasion was variaBly reduced in <B>GlycophorinB> B-deficient erythrocytes. Four strains, 3D7, HB3, Dd2, and Indochina I, invaded trypsin-treated erythrocytes, while invasion By the 7G8 strain was reduced By 90%. Among the four strains, invasion By 3D7, HB3, and Dd2 of trypsin-digested <B>GlycophorinB> B-deficient erythrocytes was further reduced. However, Indochina I invaded trypsin-digested <B>GlycophorinB> B-deficient erythrocytes at the same efficiency as its invasion of trypsin-digested normal erythrocytes. This strongly suggests that the Indochina I strain of P. falciparum is not dependent on <B>GlycophorinB> B to invade through a trypsin-resistant pathway as are the strains 3D7, HB3, and Dd2. Thus, P. falciparum is aBle to invade erythrocytes through a <B>GlycophorinB> B-independent, trypsin-resistant pathway.
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receptor and ligand domains for invasion of erythrocytes By plasmodium falciparum
Science, 1994Co-Authors: B K L Sim, Chetan E Chitnis, K Wasniowska, Terence J Hadley, Louis H. MillerAbstract:A 175-kilodalton erythrocyte Binding protein, EBA-175, of the parasite Plasmodium falciparum mediates the invasion of erythrocytes. The erythrocyte receptor for EBA-175 is dependent on sialic acid. The domain of EBA-175 that Binds erythrocytes was identified as region II with the use of truncated portions of EBA-175 expressed on COS cells. Region II, which contains a cysteine-rich motif, and native EBA-175 Bind specifically to <B>GlycophorinB> A, But not to <B>GlycophorinB> B, on the erythrocyte memBrane. Erythrocyte recognition of EBA-175 requires Both sialic acid and the peptide BackBone of <B>GlycophorinB> A. The identification of Both the receptor and ligand domains may suggest rational designs for receptor Blockade and vaccines.
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<B>GlycophorinB> B as an EBA-175 independent Plasmodium falciparum receptor of human erythrocytes
Molecular and biochemical parasitology, 1994Co-Authors: Stephen A. Dolan, Jo Lynn Proctor, David W. Alling, Yasuto Okubo, Thomas E. Wellems, Louis H. MillerAbstract:ABstract Invasion of erythrocytes By malaria parasites involves multiple receptor-ligand interactions. To elucidate these pathways, we made use of four parasite clones with differing specificities for invasion, erythrocytes that are mutant for either <B>GlycophorinB> A or B, and enzyme modification of the erythrocyte surface with neuraminidase and trypsin. Neuraminidase alone aBolishes invasion of two parasite clones (Dd2, FCR3/A2); these invade after trypsin treatment alone. A third clone (7G8) is unaBle to invade trypsin-treated erythrocytes. The fourth clone (HB3) can invade after either neuraminidase or trypsin treatment. The receptor for invasion of trypsin-treated erythrocytes was explored in two ways: treatment of trypsin-treated normal cells with neuraminidase and trypsin treatment of <B>GlycophorinB> B-deficient cells. Both treatments eliminated invasion By all clones, indicating that the trypsin-independent pathway uses sialic acid and <B>GlycophorinB> B. To identify parasite proteins involved in the different pathways, erythrocyte Binding assays were performed with soluBle parasite proteins from each clone. Based on Binding assays using erythrocytes that lack <B>GlycophorinB> A, the parasite protein known as EBA-175 appears to Bind predominantly to <B>GlycophorinB> A. In contrast, the <B>GlycophorinB> B pathway does not appear to involve EBA-175, as Binding of EBA-175 was similarly reduced to trypsin-treated normal and trypsin-treated <B>GlycophorinB> B-deficient erythrocytes. Thus, the <B>GlycophorinB> B-dependent, sialic acid-dependent invasion of trypsin-treated normal erythrocytes uses a different parasite ligand, indicating two or more sialic-dependent pathways for invasion. Clone 7G8, which cannot invade trypsin-treated erythrocytes, may Be missing the ligand for invasion via <B>GlycophorinB> B. Redundancy in the invasion process may give a selective advantage to parasites that must survive in polymorphic human populations.
M.e. Reid - One of the best experts on this subject based on the ideXlab platform.
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Murine monoclonal anti-s and other anti-<B>GlycophorinB> B antiBodies resulting from immunizations with a GPB.s peptide
EUA, 2015Co-Authors: Gr Halverson, M.e. Reid, Tossas E, Randall W. Velliquette, Lobo C, Frame T, Castilho L, Ah Lee, Grodecka MAbstract:The Blood group antigens S and s are defined By amino acids Met or Thr at position 29, respectively, on <B>GlycophorinB> B (GPB). Commercial anti-s reagents are expensive to produce Because of the scarcity of human anti-s serum. Our aim was to develop hyBridoma cell lines that secrete reagent-grade anti-s monoclonal antiBodies (MoABs) to supplement the supply of human anti-s reagents. Mice were immunized with the GPB(s) peptide sequence TKSTISSQTNGETGQLVHRF. HyBridomas were produced By fusing mouse splenocytes with mouse myeloma cells (X63.Ag8.653). Screening for antiBody production was done on microtiter plates By hemagglutination. Characterization of the MoABs was done By hemagglutination, immunoBlotting, and epitope mapping. Eight immunogloBulin G MoABs were identified. Five antiBodies are specific By hemagglutination for s and two MoABs, when diluted, are anti-S-like, But additional analyses shows a Broad range of reactivity for GPB. Typing red Blood cells (RBCs) for s from 35 donors was concordant with molecular analyses as were tests on RBCs with a positive direct antigloBulin test (DAT) from 15 patients. The anti-s MoABs are most reactive with peptides containing the (31)QLVHRF(36) motif, with (29)Thr. By Pepscan analyses, the anti-S-like MoABs reacted within the same regions as did anti-s, But independently of (29)Met. One antiBody was defined serologically as anti-U; however, its epitope was identified as (21)ISSQT(25), a sequence common for Both GPA and GPB. In addition to their value as typing reagents, these MoABs can Be used to phenotype RBCs with a positive DAT without pre-test chemical modification.49348549
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MNS Blood group system: a review
Immunohematology, 2009Co-Authors: M.e. ReidAbstract:The MNS Blood group system is second only to the Rh Blood group system in its complexity. Many alloantiBodies to antigens in the MNS system are not generally clinically significant although antiBodies to low-prevalence and high-prevalence MNS antigens have caused hemolytic disease of the fetus and newBorn. The MNS antigens are carried on <B>GlycophorinB> A (GPA), <B>GlycophorinB> B (GPB), or hyBrids thereof, which arise from single-nucleotide suBstitution, unequal crossing over, or gene conversion Between the <B>GlycophorinB> genes. Antigens in the MNS system are fully developed at Birth. This review summarizes aspects of the MNS system, including the molecular Basis of some antigens in the MNS Blood group system. Readers are referred to existing excellent reviews for Background information. Throughout this document, information given without references can Be found in the reviews listed previously, and the reader is referred to these reviews for references to original reports.
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Low-incidence MNS antigens associated with single amino acid changes and their susceptiBility to enzyme treatment.
Immunohematology, 2001Co-Authors: M.e. Reid, J R StorryAbstract:MNS antigens are carried on <B>GlycophorinB> A (GPA), <B>GlycophorinB> B (GPB), or their variants. Antigens at the N-terminus of GPA are sensitive to cleavage By ficin, papain, and trypsin But are resistant to alpha-chymotrypsin. Antigens at the N-terminus of GPB are sensitive to cleavage By ficin, papain, and alpha-chymotrypsin But are resistant to trypsin treatment. These characteristics have Been used to aid in the identification of Blood group alloantiBodies. Recent molecular analyses have identified changes in amino acids that are associated with several low-incidence antigens in the MNS Blood group system. This review relates the molecular studies with the susceptiBility or resistance of these antigens to treatment of intact red Blood cells By proteolytic enzymes.
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Characterization of antiBodies produced By S-s-individuals
Transfusion, 1996Co-Authors: Jill R. Storry, M.e. ReidAbstract:Background : Historically, classification of U- and U variant (U+ var ) individuals has Been made By hemagglutination and adsorption and elution studies performed with polyclonal U antisera. Molecular studies and serologic tests with a potent monoclonal anti-He have shown that U+ var red cells, some of which are He+, possess an altered form of <B>GlycophorinB> B. Study Design and Methods : Seventeen sera, previously determined to contain anti-U, were tested with a panel of red cells of common and rare MNS types. Results : Five sera contained anti-U only, and 12 sera contained Broadly reactive antiBodies with apparent, But inseparaBle, anti-U,He or anti-U,N,He specificities. Conclusion : The majority of antiBodies produced By S-s-U- individuals are anti-U plus anti-<B>GlycophorinB> B and are analogous to the Broadly reactive antiBodies produced By En(a-) individuals whose red cells lack <B>GlycophorinB> A or have altered <B>GlycophorinB> A. To avoid further immunization of patients with anti-U, sera used for classification of S-s-U- donors should Be selected to detect S-s- red cells that possess altered forms of <B>GlycophorinB> B.
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Expression of the erythrocyte antigen Henshaw (He; MNS6): serological and immunochemical studies
Vox sanguinis, 1995Co-Authors: M.e. Reid, G. L. Daniels, Christine Lomas-francis, V. Chen, J. Shen, V. Hare, R. Batts, M. Yacob, E. SmartAbstract:Production of murine monoclonal antiBodies to the low prevalence MNS antigen Henshaw (He; MNS6) has enaBled more detailed study of this antigen. Using these directly hemagglutinating anti-He, red Blood cells (RBCs) from 1695 people of African origin were screened in the USA and England. The prevalence of He+ samples among these donors was 2.1%. In Natal, Blood samples from 1218 Black donors were screened with raBBit anti-He. The prevalence of He+ donors in this population was 7.0%. ImmunoBlotting confirmed that the He antigen is carried on an erythrocyte memBrane component with a molecular mass that is indistinguishaBle from <B>GlycophorinB> B. Hemagglutination and immunoBlotting demonstrated that ten of 56 He+ samples tested more extensively had a reduced expression of the He antigen. The majority of He+ RBCs were S+; those He+ RBC samples that were S-s+ more frequently had a weakened expression of He.
Kate Hsu - One of the best experts on this subject based on the ideXlab platform.
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Exploring the Potential Roles of Band 3 and Aquaporin-1 in Blood CO2 Transport-Inspired By Comparative Studies of <B>GlycophorinB> B-A-B HyBrid Protein GP.Mur.
Frontiers in physiology, 2018Co-Authors: Kate HsuAbstract:The Cl-/HCO3- exchanger Band 3 is functionally relevant to Blood CO2 transport. Band 3 is the most aBundant memBrane protein in human red Blood cells (RBCs). Our understanding of its physiological functions mainly came from clinical cases associated with Band 3 mutations. Severe reduction in Band 3 expression affects Blood HCO3-/CO2 metaBolism. What could happen physiologically if Band 3 expression is elevated instead? In some areas of Southeast Asia, aBout 1 - 10% of the populations express GP.Mur, a <B>GlycophorinB> B-A-B hyBrid memBrane protein important in the field of transfusion medicine. GP.Mur functions to promote Band 3 expression, and GP.Mur red cells can Be deemed as a naturally-occurred model for higher Band 3 expression. This review first compares the functional consequences of Band 3 at different levels, and suggests a critical role of Band 3 in postnatal CO2 respiration. The second part of the review explores the transport of water, which is the other suBstrate for intra-erythrocytic CO2/HCO3- conversion (an essential step in Blood CO2 transport). Despite that water is considered unlimited physiologically, it is unclear whether water channel aquaporin-1 (AQP1) aBundantly expressed in RBCs is functionally involved in CO2 transport. Research in this area is complicated By the fact that the H2O/CO2-transporting function of AQP1 is replaceaBle By other erythrocyte channels/transporters (e.g. UT-B/GLUT1 for H2O; RhAG for CO2). Recently, using carBonic anhydrase II (CAII)-filled erythrocyte vesicles, AQP1 has Been demonstrated to transport water for the CAII-mediated reaction, CO2(g) + H2O ⇌ HCO3-(aq) + H+(aq). AQP1 is structurally associated with some population of Band 3 complexes on the erythrocyte memBrane in an osmotically-responsive fashion. The current findings reveal transient interaction among components within the Band 3-central, CO2-transport metaBolon (AQP1, Band 3, CAII and deoxygenated hemogloBin). Their dynamic interaction is envisioned to facilitate Blood CO2 respiration, in the presence of constantly-changing osmotic and hemodynamic stresses during circulation.
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Exploring the Potential Roles of Band 3 and Aquaporin-1 in Blood CO2 Transport–Inspired By Comparative Studies of <B>GlycophorinB> B-A-B HyBrid Protein GP.Mur
Frontiers Media S.A., 2018Co-Authors: Kate HsuAbstract:The Cl—/HCO3— exchanger Band 3 is functionally relevant to Blood CO2 transport. Band 3 is the most aBundant memBrane protein in human red Blood cells (RBCs). Our understanding of its physiological functions mainly came from clinical cases associated with Band 3 mutations. Severe reduction in Band 3 expression affects Blood HCO3—/CO2 metaBolism. What could happen physiologically if Band 3 expression is elevated instead? In some areas of Southeast Asia, aBout 1–10% of the populations express GP.Mur, a <B>GlycophorinB> B-A-B hyBrid memBrane protein important in the field of transfusion medicine. GP.Mur functions to promote Band 3 expression, and GP.Mur red cells can Be deemed as a naturally occurred model for higher Band 3 expression. This review first compares the functional consequences of Band 3 at different levels, and suggests a critical role of Band 3 in postnatal CO2 respiration. The second part of the review explores the transport of water, which is the other suBstrate for intra-erythrocytic CO2/HCO3— conversion (an essential step in Blood CO2 transport). Despite that water is considered unlimited physiologically, it is unclear whether water channel aquaporin-1 (AQP1) aBundantly expressed in RBCs is functionally involved in CO2 transport. Research in this area is complicated By the fact that the H2O/CO2-transporting function of AQP1 is replaceaBle By other erythrocyte channels/transporters (e.g., UT-B/GLUT1 for H2O; RhAG for CO2). Recently, using carBonic anhydrase II (CAII)-filled erythrocyte vesicles, AQP1 has Been demonstrated to transport water for the CAII-mediated reaction, CO2(g) + H2O ⇌ HCO3—(aq) + H+(aq). AQP1 is structurally associated with some population of Band 3 complexes on the erythrocyte memBrane in an osmotically responsive fashion. The current findings reveal transient interaction among components within the Band 3-central, CO2-transport metaBolon (AQP1, Band 3, CAII and deoxygenated hemogloBin). Their dynamic interaction is envisioned to facilitate Blood CO2 respiration, in the presence of constantly changing osmotic and hemodynamic stresses during circulation
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The MNS <B>GlycophorinB> variant GP.Mur affects differential erythroid expression of Rh/RhAG transcripts.
Vox sanguinis, 2017Co-Authors: Kate Hsu, M.-s. Kuo, C.-c. Yao, H.-c. Cheng, Hui-ju Lin, Y.-s. Chan, M. LinAbstract:Background The Band 3 macrocomplex (also known as the ankyrin-associated complex) on the red cell memBrane comprises two interacting suBcomplexes: a Band 3/<B>GlycophorinB> A suBcomplex, and a Rh/RhAG suBcomplex. <B>GlycophorinB> B (GPB) is a component of the Rh/RhAG suBcomplex that is also structurally associated with <B>GlycophorinB> A (GPA). Expression of <B>GlycophorinB> B-A-B hyBrid GP.Mur enhances Band 3 expression and is associated with lower levels of Rh-associated glycoprotein (RhAG) and Rh polypeptides. The goal of this study was to determine whether GP.Mur influenced erythroid Rh/RhAG expression at the transcript level. Materials and Methods GP.Mur was serologically determined in healthy participants from Taitung County, Taiwan. RNA was extracted from the reticulocyte-enriched fraction of peripheral Blood, followed By reverse transcription and quantitative PCR for RhAG, RhD and RhCcEe. Results Quantification By real-time PCR revealed significantly fewer RhAG and RhCcEe transcripts in the reticulocytes from suBjects with homozygous GYP*Mur. Independent from GYP.Mur, Both RhAG and RhD transcript levels were threefold or higher than that of RhCcEe. Also, in GYP.Mur and the control samples alike, direct quantitative associations were oBserved Between the transcript levels of RhAG and RhD, But not Between that of RhAG and RhCcEe. Conclusion Erythroid RhD and RhCcEe were differentially expressed at the transcript levels, which could Be related to their different degrees of interaction or sensitivity to RhAG. Further, the reduction or aBsence of <B>GlycophorinB> B in GYP.Mur erythroid cells affected transcript expressions of RhAG and RhCcEe. Thus, GPB and GP.Mur differentially influenced Rh/RhAG expressions prior to protein translation.
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Dissecting alternative splicing in the formation of MiltenBerger <B>GlycophorinB> suBtype III (GYP.Mur)
Vox sanguinis, 2015Co-Authors: Kate Hsu, C.-c. Yao, Yen-chun Lin, C.‐l. Chang, Ting-ying LeeAbstract:Background and OBjectives MiltenBerger suBtype III (Mi.III, GP.Mur) is one of the most important red cell phenotypes in the fields of transfusion in South-East Asia. GP.Mur is Believed to evolve from homologous gene recomBination events Between <B>GlycophorinB> A (GYPA) and <B>GlycophorinB> B (GYPB). GYP.Mur differs from GYPB in only seven nucleotides dispersed near the region of 3′ exon 3 of GYP.Mur. The goal of this study was to dissect how these nucleotide variants affected splicing of exon 3. Materials and Methods We first designed two minigene constructs: one containing GYP.Mur from exon 2 to exon 4 and the other containing GYPB in the same region. To test how these nucleotide variations Between GYP.Mur and GYPB affected the splicing, a repertoire of the GYP.Mur-like minigene constructs with different point mutations were created. These minigene variants were evaluated for their aBilities to induce splicing of exon 3 using a heterologous expression system. Results (1) GYP.Mur minigene expressed exons 2, 3 and 4, whereas GYPB minigene expressed only exon 2 and exon 4. (2) The single nucleotide alteration at the position of the 5′ splice site of <B>GlycophorinB> intron 3 reversed the splicing decision. (3) The nucleotide variations Between GYP.Mur and GYPB other than that at the 5′ splice site showed very little or no effect on splicing of exon 3. Conclusion Splicing of the <B>GlycophorinB> B-A-B hyBrids (GYP.Mur and GYP.BUN) and unsplicing of GYPB follow the GU-AG rule strictly.
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The cholesterol content in erythrocytes expressing MiltenBerger antigen suBtype III (Mi.III) has limited effects on memBrane deformaBility (LB161)
The FASEB Journal, 2014Co-Authors: Kate Hsu, Chin-che YaoAbstract:The MiltenBerger antigen suBtype III (Mi.III, GP.Mur), is one of the most important red Blood cell (RBC) antigens in Southeast Asia. GP.Mur is a <B>GlycophorinB> B-A-B fusion protein evolved from homologous recomBination of <B>GlycophorinB> A and <B>GlycophorinB> B. We previously showed that GP.Mur in Mi.III+ cells enhances the expression of Band 3, consequently facilitating Cl-/HCO3- transport, CO2 respiration, and memBrane resistance to osmotic stress. The aim of this study was to further investigate if the unique expressions of GP.Mur and Band 3 in Mi.III also influenced cell memBrane deformaBility. The methods utilized were osmotic gradient ektacytometry, osmotic fragility tests and Amplex Red Cholesterol assay. A total of 114 fresh RBC samples, including 50 Mi.III+ and 64 non-Mi.III (control), were evaluated. From osmolarity fragility tests, Mi.III+ RBCs consistently exhiBited superior resistance to osmotic stress. Mi.III+ RBCs however were less deformaBle than the control cells. The discordance Between the results...
Jennifer K Thompson - One of the best experts on this subject based on the ideXlab platform.
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a novel erythrocyte Binding antigen 175 paralogue from plasmodium falciparum defines a new trypsin resistant receptor on human erythrocytes
Journal of Biological Chemistry, 2003Co-Authors: Timwolf Gilberger, Manoj T Duraisingh, Jennifer K Thompson, Tony Triglia, Robert T Good, Alan F CowmanAbstract:ABstract The recognition and invasion of human erythrocytes By the most lethal malaria parasite Plasmodium falciparum is dependent on multiple ligand-receptor interactions. MemBers of the erythrocyte Binding-like (eBl) family, including the erythrocyte Binding antigen-175 (EBA-175), are responsiBle for high affinity Binding to glycoproteins on the surface of the erythrocyte. Here we descriBe a paralogue of EBA-175 and show that this protein (EBA-181/JESEBL) Binds in a sialic acid-dependent manner to erythrocytes. EBA-181 is expressed at the same time as EBA-175 and co-localizes with this protein in the microneme organelles of asexual stage parasites. The receptor Binding specificity of EBA-181 to erythrocytes differs from other memBers of the eBl family and is trypsin-resistant and chymotrypsin-sensitive. Furthermore, using <B>GlycophorinB> B-deficient erythrocytes we show that Binding of EBA-181 is not dependent on this sialoglycoprotein. The level of expression of EBA-181 differs among parasite lines, and the importance of this ligand for invasion appears to Be strain-dependent as the EBA-181 gene can Be disrupted in W2mef parasites, without affecting the invasion phenotype, But cannot Be targeted in 3D7 parasites.
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a novel erythrocyte Binding antigen 175 paralogue fromplasmodium falciparum defines a new trypsin resistant receptor on human erythrocytes
Journal of Biological Chemistry, 2003Co-Authors: Timwolf Gilberger, Manoj T Duraisingh, Jennifer K Thompson, Tony Triglia, Robert T Good, Alan F CowmanAbstract:The recognition and invasion of human erythrocytes By the most lethal malaria parasite Plasmodium falciparum is dependent on multiple ligand-receptor interactions. MemBers of the erythrocyte Binding-like (eBl) family, including the erythrocyte Binding antigen-175 (EBA-175), are responsiBle for high affinity Binding to glycoproteins on the surface of the erythrocyte. Here we descriBe a paralogue of EBA-175 and show that this protein (EBA-181/JESEBL) Binds in a sialic acid-dependent manner to erythrocytes. EBA-181 is expressed at the same time as EBA-175 and co-localizes with this protein in the microneme organelles of asexual stage parasites. The receptor Binding specificity of EBA-181 to erythrocytes differs from other memBers of the eBl family and is trypsin-resistant and chymotrypsin-sensitive. Furthermore, using <B>GlycophorinB> B-deficient erythrocytes we show that Binding of EBA-181 is not dependent on this sialoglycoprotein. The level of expression of EBA-181 differs among parasite lines, and the importance of this ligand for invasion appears to Be strain-dependent as the EBA-181 gene can Be disrupted in W2mef parasites, without affecting the invasion phenotype, But cannot Be targeted in 3D7 parasites.
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A novel ligand from Plasmodium falciparum that Binds to a sialic acid-containing receptor on the surface of human erythrocytes.
Molecular microbiology, 2001Co-Authors: Jennifer K Thompson, Tony Triglia, Michael B. Reed, Alan F CowmanAbstract:Summary Invasion of the merozoite form of Plasmodium falciparum into human erythrocytes involves multiple receptor‐ligand interactions. The EBA175 protein of P. falciparum has Been shown to Be the ligand that Binds to a sialic acid-dependent site on <B>GlycophorinB> A. We have identified a novel P. falciparum ligand, termed erythrocyte-Binding antigen 140 (EBA140), that shares structural features and homology with EBA175. SuBcellular localization of EBA140 suggests that it is located in the micronemes, the same localization as EBA175. EBA140 Binds to a sialic acid-dependent receptor on the surface of human erythrocytes. Binding of EBA140 to this erythrocyte receptor is sensitive to neuraminidase and resistant to trypsin, proteinase K and pronase. The proteaseresistant properties of the erythrocyte receptor suggests that it is not <B>GlycophorinB> A or C. Additionally, analysis of mutant erythrocytes from humans has shown that EBA140 does not Bind <B>GlycophorinB> B. Interestingly, we have identified a parasite line that lacks the eBa140 gene, suggesting that this protein is not essential for in vitro invasion. These results suggest that EBA140 may Be involved in merozoite invasion using a sialic acid-dependent receptor on human erythrocytes.