Molecular Basis of Red Cell Membrane Disorders

Delaunay, Jean

doi:10.1159/000065657

Cited by 79 publications

(59 citation statements)

References 16 publications

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“…Red blood cell membrane and cytoskeletal proteins make up the components of the filamentous meshwork of proteins along the cytoplasmic surface of the membrane necessary for mechanical stability, normal morphology, and flexibility (22). Dominant mutations in ANK1, SPTA1, SPTB, SLC4A1, EPB42, and EPB41 cause hereditary spherocytosis or elliptocytosis, characterized by poor membrane stability, abnormal morphology, and a high rate of red cell turnover (23,24). The important function of these proteins implies that their expression must be well conserved among species.…”

Section: Resultsmentioning

confidence: 99%

Transcriptional divergence and conservation of human and mouse erythropoiesis

Pishesha

Thiru

Shi

et al. 2014

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

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Significance Mouse models have been instrumental in advancing our understanding of blood cell production. Although many studies have suggested specific differences between human and mouse red cell production (erythropoiesis), a global study of such similarities and differences has been lacking. By computationally comparing global gene expression data from adult human and mouse erythroid precursors representing the distinct stages of maturation, we showed that, while the overall transcriptional landscape has changed, critical erythroid gene signatures and transcriptional regulators have remained conserved. Importantly, these analyses can serve as a tool to integrate data between human and mouse erythropoiesis research, explain why certain human blood diseases are not faithfully recapitulated in mouse models, and highlight hurdles in translating therapeutic findings from mice to humans.

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Section: Resultsmentioning

confidence: 99%

Transcriptional divergence and conservation of human and mouse erythropoiesis

Pishesha

Thiru

Shi

et al. 2014

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

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“…As expected from comparative analysis of mouse band 3 cDNA sequence (28) and the amino acid polymorphism associated with the Di a /Di b blood group polymorphism in man (P854L) (29), mouse band 3 could be detected by the anti-Di b but not the anti-Di a mAb. 3 To check the permeabilization efficiency, actin staining was performed on all cells at room temperature with 10 l of phalloidin-fluorescein isothiocyanate (Sigma).…”

Section: Methodsmentioning

confidence: 99%

“…According to a model in which ankyrin-R plays a pivotal role for expression of both band 3 and the Rh complex, flow cytometric and Western blot analysis indicate that band 3 expression is not altered in Rh null cells and that these cells contain a normal amount of ankyrin. 3 Interestingly, the Asp-399 residue of the cytoplasmic tail of RhAG was previously reported to be mutated in one Rh null patient (11). On the other hand, it has been shown that the binding of band 3 to the D2 domain of ankyrin-R might be mediated by electrostatic contacts (39).…”

Section: Fig 4 Yeast Two-hybrid Analysis Of the Interaction Betweenmentioning

confidence: 99%

“…This is evidenced by the morphological abnormalities of the RBC that result in hemolytic anemia of varying severity (hereditary elliptocytosis (HE), pyropoikilocytosis (HPP), spherocytosis (HS), and ovalo-stomatocytosis (SAO). These abnormalities are associated with mutations of different skeletal and integral membrane proteins that alter "horizontal" or "vertical" protein/protein interactions (3). The band 3-ankyrin protein 4.2 and the glycophorin C (GPC) protein 4.1-p55 complexes represent well characterized major attachment sites between the membrane bilayer and the red cell skeleton (4,5).…”

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confidence: 99%

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Rh-RhAG/Ankyrin-R, a New Interaction Site between the Membrane Bilayer and the Red Cell Skeleton, Is Impaired by Rhnull-associated Mutation

Nicolas

Kim

Gane

et al. 2003

Journal of Biological Chemistry

118

109

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Several studies suggest that the Rh complex represents a major interaction site between the membrane lipid bilayer and the red cell skeleton, but little is known about the molecular basis of this interaction. We report here that ankyrin-R is capable of interacting directly with the C-terminal cytoplasmic domain of Rh and RhAG polypeptides. We first show that the primary defect of ankyrin-R in normoblastosis (nb/nb) spherocytosis mutant mice is associated with a sharp reduction of RhAG and Rh polypeptides. Secondly, our flow cytometric analysis of the Triton X-100 extractability of recombinant fusion proteins expressed in erythroleukemic cell lines suggests that the C-terminal cytoplasmic domains of Rh and RhAG are sufficient to mediate interaction with the erythroid membrane skeleton. Using the yeast two-hybrid system, we demonstrate a direct interaction between the cytoplasmic tails of Rh and RhAG and the second repeat domain (D2) of ankyrin-R. This finding is supported by the demonstration that the substitution of Asp-399 in the cytoplasmic tail of RhAG, a mutation associated with the deficiency of the Rh complex in one Rh null patient, totally impaired interaction with domain D2 of ankyrin-R. These results identify the Rh/RhAG-ankyrin complex as a new interaction site between the red cell membrane and the spectrin-based skeleton, the disruption of which might result in the stomato-spherocytosis typical of Rh null red cells.

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“…Hereditary spherocytosis is a spectrum of inherited diseases, occurring in one family out of 2,000 -3,000, which present clinically as varying degrees of hemolytic anemia resulting from hemolysis of the spherical erythrocytes as they flow through the microcirculation. Recent data have indicated that 15-20% of hereditary spherocytosis cases are attributable to AE1 mutations and that ϳ50% of hereditary spherocytosis cases result from ankyrin-R mutations (1).…”

mentioning

confidence: 99%

Determination of Structural Models of the Complex between the Cytoplasmic Domain of Erythrocyte Band 3 and Ankyrin-R Repeats 13–24

Kim

Brandon

Zhou

et al. 2011

Journal of Biological Chemistry

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The adaptor protein ankyrin-R interacts via its membrane binding domain with the cytoplasmic domain of the anion exchange protein (AE1) and via its spectrin binding domain with the spectrin-based membrane skeleton in human erythrocytes. This set of interactions provides a bridge between the lipid bilayer and the membrane skeleton, thereby stabilizing the membrane. Crystal structures for the dimeric cytoplasmic domain of AE1 (cdb3) and for a 12-ankyrin repeat segment (repeats 13-24) from the membrane binding domain of ankyrin-R (AnkD34) have been reported. However, structural data on how these proteins assemble to form a stable complex have not been reported. In the current studies, site-directed spin labeling, in combination with electron paramagnetic resonance (EPR) and double electron-electron resonance, has been utilized to map the binding interfaces of the two proteins in the complex and to obtain inter-protein distance constraints. These data have been utilized to construct a family of structural models that are consistent with the full range of experimental data. These models indicate that an extensive area on the peripheral domain of cdb3 binds to ankyrin repeats 18 -20 on the top loop surface of AnkD34 primarily through hydrophobic interactions. This is a previously uncharacterized surface for binding of cdb3 to AnkD34. Because a second dimer of cdb3 is known to bind to ankyrin repeats 7-12 of the membrane binding domain of ankyrin-R, the current models have significant implications regarding the structural nature of a tetrameric form of AE1 that is hypothesized to be involved in binding to full-length ankyrin-R in the erythrocyte membrane.Human erythrocytes exhibit an unusual biconcave disc shape and remarkable plasma membrane mechanical stability and deformability, all of which are necessary for their survival in the circulatory system. It is now well established that the unusual cell shape and membrane mechanical properties are due in large part to the presence of an extensive membrane skeleton, composed primarily of the proteins spectrin and actin, that lines the inner membrane surface and to specific bridging interactions between this membrane skeleton and intrinsic membrane proteins in the lipid bilayer. The spectrin-actin skeleton associates with the membrane bilayer via two types of contacts, one involving short actin protofilaments and protein 4.1, which interact with the cytoplasmic domain of glycophorin C, and the second involving the bridging protein ankyrin-R and protein 4.2, which interact with the cytoplasmic domain of the anion exchange protein (AE1) 3 also known as band 3. Alterations in this second class of interactions often result in spherical erythrocytes with decreased cell size and increased fragility, a condition known clinically as hereditary spherocytosis. Hereditary spherocytosis is a spectrum of inherited diseases, occurring in one family out of 2,000 -3,000, which present clinically as varying degrees of hemolytic anemia resulting from hemolysis of the spherical erythrocytes ...

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Molecular Basis of Red Cell Membrane Disorders

Cited by 79 publications

References 16 publications

Transcriptional divergence and conservation of human and mouse erythropoiesis

Transcriptional divergence and conservation of human and mouse erythropoiesis

Rh-RhAG/Ankyrin-R, a New Interaction Site between the Membrane Bilayer and the Red Cell Skeleton, Is Impaired by Rhnull-associated Mutation

Determination of Structural Models of the Complex between the Cytoplasmic Domain of Erythrocyte Band 3 and Ankyrin-R Repeats 13–24

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