Murine recessive hereditary spherocytosis, sph/sph, is caused by a mutation in the erythroid α-spectrin gene

Wandersee, Nancy J.; Birkenmeier, Connie S.; Gifford, Elaine J; Mohandas, Narla; Barker, Jane E.

doi:10.1038/sj.thj.6200030

Cited by 27 publications

(28 citation statements)

References 24 publications

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“…These mice have primary defects in Ank1 (nb͞nb) (44) or ␣-spectrin (sph͞sph) (45). RBCs from nb͞nb mice exhibit a sharp reduction of Rh and Rhag proteins but normal levels of CD47 (7), which is also true for RBCs from sph͞sph mice (Table 4).…”

Section: Ch3nh2͞nh3 Transport Of Ghosts From Mutant Micementioning

confidence: 78%

Human Rhesus-associated glycoprotein mediates facilitated transport of NH ₃ into red blood cells

Ripoche

Bertrand

Gane

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

148

154

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Section: Ch3nh2͞nh3 Transport Of Ghosts From Mutant Micementioning

confidence: 78%

Human Rhesus-associated glycoprotein mediates facilitated transport of NH ₃ into red blood cells

Ripoche

Bertrand

Gane

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

148

154

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“…The N-terminal domain of the spectrin ␤-chain, to which the C-terminal part of the ␣-chain is linked, is sufficient to generate the ternary complex in vitro (20), and what we have observed here hints at a possible participation of the ␣-chain in the junction complex. This has indeed been suggested on the basis of the properties of erythrocytes of sph J mice, in which the C-terminal 13 amino acids of ␣-spectrin were deleted (27). We cannot, at the same time, exclude that the effect of PfEMP3 or its active fragment in weakening the junction by binding to ␣-spectrin may be due to steric crowding.…”

Section: Discussionmentioning

confidence: 92%

Plasmodium falciparum Erythrocyte Membrane Protein 3 (PfEMP3) Destabilizes Erythrocyte Membrane Skeleton

Pei

Guo

Coppel

et al. 2007

Journal of Biological Chemistry

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Plasmodium falciparum erythrocyte membrane protein 3 (PfEMP3) is a parasite-derived protein that appears on the cytoplasmic surface of the host cell membrane in the later stages of the parasite's development where it associates with membrane skeleton. We have recently demonstrated that a 60-residue fragment (FIa1, residues 38 -97) of PfEMP3 bound to spectrin. Here we show that this polypeptide binds specifically to a site near the C terminus of ␣-spectrin at the point that spectrin attaches to actin and protein 4.1R in forming the junctions of the membrane skeletal network. We further show that this polypeptide disrupts formation of the ternary spectrin-actin-4.1R complex in solution. Importantly, when incorporated into the cell, the PfEMP3 fragment causes extensive reduction in shear resistance of the cell. We conjecture that the loss of mechanical cohesion of the membrane may facilitate the exit of the mature merozoites from the cell.The intraerythrocytic form of Plasmodium falciparum, the agent of the most severe type of human malaria, exports many (according to a proteomic estimate, up to 400) proteins into the host cell in the course of its growth and development (1-3). Certain of these proteins are known to associate with the host cell membrane skeleton and thereby modify its structure and properties. Among the changes that have been reported are an altered morphology, an increased membrane rigidity, and an enhanced propensity to adhere to the vascular endothelium (4). Several such proteins that bind to the red cell membrane skeleton have so far been characterized. When the parasite first invades red cells, it deposits RESA (the ring parasite-infected erythrocyte surface antigen) at the membrane skeleton of the newly invaded cell where it binds to spectrin and protects against thermal damage (5-7). As the intracellular parasite further matures, it traffics further proteins to the skeleton. P. falciparum erythrocyte membrane protein 1, or PfEMP1, 2 is inserted into the red cell membrane and its extracellular domain adheres to receptors on endothelial cells (8). PfEMP1 clusters on the red cell surface at dimpled areas called knobs by binding of its intracellular domain to the parasite-encoded protein KAHRP (knob-associated histidine-rich protein) from which knobs are formed (9) and to spectrin and actin (10). KAHRP itself is stabilized at the membrane by interactions with the fourth repeat of spectrin ␣-chain (11). MESA (the mature parasite-infected erythrocyte surface antigen) binds to the 30-kDa domain of protein 4.1R and displaces the host protein p55 (12, 13). Its role in parasite biology is still uncertain, but interference with MESA binding is lethal to the parasite (14). The P. falciparum erythrocyte membrane protein 3 (PfEMP3), with which we are concerned here, is a large protein of 315 kDa that is expressed from the late ring stage onward and is exported via the Maurer's clefts, vesicular structures of parasite origin, into the cytoplasm of the red cell, where it associates with membrane skeleton. H...

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“…In the present study, we demonstrate that (1) GEs are indeed localized to the membrane in oxygenated murine erythrocytes, (2) GEs release from the membrane upon deoxygenation of the mouse red cells, (3) GEs are cytosolic in both oxygenated and deoxygenated erythrocytes from band 3 knockout mice, 9 (4) GEs are displaced from the membrane by antibodies to the cytoplasmic domain of band 3 and by recombinant cytoplasmic domain of band 3 itself, and (5) GEs are largely membrane localized in mature oxygenated cells from mice deficient in protein 4.2, 10 ␤-adducin, 11 protein 4.1, 12 dematin headpiece domain, 13 ankyrin (nb/nb), 14 and ␣-spectrin (sph/sph). 15 These data suggest that GE associations with erythrocyte membranes could represent a widespread phenomenon and that the stability of these interactions depends primarily on the presence of band 3.…”

Section: Introductionmentioning

confidence: 91%

“…To determine whether other membrane proteins might be similarly essential for GE organization on the membrane, erythrocytes from knockout mice for protein 4.2, 10 ␤-adducin, 11 protein 4.1, 12 and dematin, 13 as well as red cells from mice containing spontaneous hypomorphic mutations leading to nearly quantitative deficiencies in ankyrin (nb/nb mice) 14 and ␣-spectrin (sph/sph mice) 15 were also examined. In contrast to membranes lacking band 3, GEs in these other defective erythrocytes still exhibit various extents of membrane localization, suggesting that the essential components of their membrane binding sites remain intact (Figures 6, 7, S2).…”

Section: Band 3 Is the Center Of Enzyme Organization On The Erythrocymentioning

confidence: 99%

Characterization of glycolytic enzyme interactions with murine erythrocyte membranes in wild-type and membrane protein knockout mice

Campanella

Chu

Wandersee

et al. 2008

Blood

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Previous research has shown that glycolytic enzymes (GEs) exist as multienzyme complexes on the inner surface of human erythrocyte membranes. Because GE binding sites have been mapped to sequences on the membrane protein, band 3, that are not conserved in other mammalian homologs, the question arose whether GEs can organize into complexes on other mammalian erythrocyte membranes. To address this, murine erythrocytes were stained with antibodies to glyceraldehyde-3-phosphate dehydrogenase, aldolase, phosphofructokinase, lactate dehydrogenase, and pyruvate kinase and analyzed by confocal microscopy. GEs were found to localize to the membrane in oxygenated erythrocytes but redistributed to the cytoplasm upon deoxygenation, as seen in human erythrocytes. To identify membrane proteins involved in GE assembly, erythrocytes from mice lacking each of the major erythrocyte membrane proteins were examined for GE localization. GEs from band 3 knockout mice were not membrane associated but distributed throughout the cytoplasm, regardless of erythrocyte oxygenation state. In contrast, erythrocytes from mice lacking ␣-spectrin, ankyrin, protein 4.2, protein 4.1, ␤-adducin, or dematin headpiece exhibited GEs bound to the membrane. These data suggest that oxygenation-dependent assembly of GEs on the membrane could be a general phenomenon of mammalian erythrocytes and that stability of these interactions depends primarily on band 3. (Blood. 2008;112:3900-3906)

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Murine recessive hereditary spherocytosis, sph/sph, is caused by a mutation in the erythroid α-spectrin gene

Abstract: These results predict the heart as an additional site where alpha-spectrin mutations may produce a phenotype and raise the possibility that a novel functional class of small alpha-spectrin isoforms may exist.

Cited by 27 publications

References 24 publications

Human Rhesus-associated glycoprotein mediates facilitated transport of NH ₃ into red blood cells

Human Rhesus-associated glycoprotein mediates facilitated transport of NH ₃ into red blood cells

Plasmodium falciparum Erythrocyte Membrane Protein 3 (PfEMP3) Destabilizes Erythrocyte Membrane Skeleton

Characterization of glycolytic enzyme interactions with murine erythrocyte membranes in wild-type and membrane protein knockout mice

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Murine recessive hereditary spherocytosis, sph/sph, is caused by a mutation in the erythroid α-spectrin gene

Abstract: These results predict the heart as an additional site where alpha-spectrin mutations may produce a phenotype and raise the possibility that a novel functional class of small alpha-spectrin isoforms may exist.

Cited by 27 publications

References 24 publications

Human Rhesus-associated glycoprotein mediates facilitated transport of NH 3 into red blood cells

Human Rhesus-associated glycoprotein mediates facilitated transport of NH 3 into red blood cells

Plasmodium falciparum Erythrocyte Membrane Protein 3 (PfEMP3) Destabilizes Erythrocyte Membrane Skeleton

Characterization of glycolytic enzyme interactions with murine erythrocyte membranes in wild-type and membrane protein knockout mice

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Human Rhesus-associated glycoprotein mediates facilitated transport of NH ₃ into red blood cells

Human Rhesus-associated glycoprotein mediates facilitated transport of NH ₃ into red blood cells