scholarly journals Identification of a functional role for human erythrocyte sialoglycoproteins beta and gamma

Blood ◽  
1987 ◽  
Vol 69 (4) ◽  
pp. 1068-1072
Author(s):  
ME Reid ◽  
JA Chasis ◽  
N Mohandas
Keyword(s):  
Erythrocyte Membrane ◽  
Material Properties ◽  
Functional Role ◽  
Mechanical Stability ◽  
Membrane Skeleton ◽  
Membrane Properties ◽  
Membrane Material ◽  
Skeletal Protein ◽  
Alpha Beta ◽  
Normal Erythrocyte

Four distinct erythrocyte membrane sialoglycoproteins (SGPs) denoted alpha, beta, gamma, and delta have been described, but their functions have not yet been defined. Recent evidence suggests that several of these SGPs associate with membrane skeletal proteins. Because the membrane skeletal protein network plays an important role in regulating the membrane material properties of deformability and mechanical stability, we wanted to determine whether the SGPs, through their interaction with the membrane skeleton, can modulate these membrane properties. We measured membrane mechanical stability and membrane deformability of erythrocytes that were deficient in either alpha, or delta or beta and gamma SGPs. Only erythrocytes deficient in beta and gamma SGP had altered membrane properties, as evidenced by marked decreases in both membrane mechanical stability (50% of normal) and membrane deformability (40% of normal). Erythrocytes deficient in either alpha or delta SGP had normal deformability and stability. Based on these data, we suggest that an interaction of beta and/or gamma SGP with the membrane skeleton plays a functionally important role in regulating normal erythrocyte membrane properties.

scholarly journals Identification of a functional role for human erythrocyte sialoglycoproteins beta and gamma

Blood ◽  
1987 ◽  
Vol 69 (4) ◽  
pp. 1068-1072 ◽  
Author(s):  
ME Reid ◽  
JA Chasis ◽  
N Mohandas
Keyword(s):  
Erythrocyte Membrane ◽  
Material Properties ◽  
Functional Role ◽  
Mechanical Stability ◽  
Membrane Skeleton ◽  
Membrane Properties ◽  
Membrane Material ◽  
Skeletal Protein ◽  
Alpha Beta ◽  
Normal Erythrocyte

Abstract Four distinct erythrocyte membrane sialoglycoproteins (SGPs) denoted alpha, beta, gamma, and delta have been described, but their functions have not yet been defined. Recent evidence suggests that several of these SGPs associate with membrane skeletal proteins. Because the membrane skeletal protein network plays an important role in regulating the membrane material properties of deformability and mechanical stability, we wanted to determine whether the SGPs, through their interaction with the membrane skeleton, can modulate these membrane properties. We measured membrane mechanical stability and membrane deformability of erythrocytes that were deficient in either alpha, or delta or beta and gamma SGPs. Only erythrocytes deficient in beta and gamma SGP had altered membrane properties, as evidenced by marked decreases in both membrane mechanical stability (50% of normal) and membrane deformability (40% of normal). Erythrocytes deficient in either alpha or delta SGP had normal deformability and stability. Based on these data, we suggest that an interaction of beta and/or gamma SGP with the membrane skeleton plays a functionally important role in regulating normal erythrocyte membrane properties.

scholarly journals Disorders of the erythrocyte membrane

2015 ◽  
Vol 9 (4) ◽  
pp. 323
Author(s):  
Sophia Delicou ◽  
Aikaterini Xydaki ◽  
Chryssanthi Kontaxi ◽  
Konstantinos Maragkos
Keyword(s):  
Surface Area ◽  
Erythrocyte Membrane ◽  
Structural Integrity ◽  
Mechanical Stability ◽  
Hereditary Spherocytosis ◽  
Membrane Surface ◽  
Membrane Skeleton ◽  
Inherited Disorders ◽  
Hereditary Elliptocytosis ◽  
Area Loss

Hemolytic anemia due to abnormalities of the erythrocyte membrane comprises an important group of inherited disorders. These include hereditary spherocytosis, hereditary elliptocytosis, hereditary pyropoikilocytosis, and the hereditary stomatocytosis syndromes. The erythrocyte membrane skeleton composed of spectrin, actin, and several other proteins is essential for the maintenance of the erythrocyte shape, reversible deformability, and membrane structural integrity in addition to controlling the lateral mobility of integral membrane proteins. These disorders are characterized by clinical and laboratory heterogeneity and, as evidenced by recent molecular studies, by genetic heterogeneity. Defects in various proteins involved in linking the lipid bilayer to membrane skeleton result in loss in membrane cohesion leading to surface area loss and hereditary spherocytosis while defects in proteins involved in lateral interactions of the spectrin-based skeleton lead to decreased mechanical stability, membrane fragmentation and hereditary elliptocytosis. The disease severity is primarily dependent on the extent of membrane surface area loss. Treatment with splenectomy is curative in most patients.

scholarly journals Erythrocyte membrane deformability and stability: two distinct membrane properties that are independently regulated by skeletal protein associations.

1986 ◽  
Vol 103 (2) ◽  
pp. 343-350 ◽  
Author(s):  
J A Chasis ◽  
N Mohandas
Keyword(s):  
Erythrocyte Membrane ◽  
Protein Interactions ◽  
Membrane Properties ◽  
Protein 4.1 ◽  
Stability Change ◽  
Skeletal Protein ◽  
Self Association ◽  
The Stability ◽  
Distinct Membrane

Skeletal proteins play an important role in determining erythrocyte membrane biophysical properties. To study whether membrane deformability and stability are regulated by the same or different skeletal protein interactions, we measured these two properties, by means of ektacytometry, in biochemically perturbed normal membranes and in membranes from individuals with known erythrocyte abnormalities. Treatment with 2,3-diphosphoglycerate resulted in membranes with decreased deformability and decreased stability, whereas treatment with diamide produced decreased deformability but increased stability. N-ethylmaleimide induced time-dependent changes in membrane stability. Over the first minute, the stability increased; but with continued incubation, the membranes became less stable than control. Meanwhile, the deformability of these membranes decreased with no time dependence. Biophysical measurements were also carried out on pathologic erythrocytes. Membranes from an individual with hereditary spherocytosis and a defined abnormality in spectrin-protein 4.1 association showed decreased stability but normal deformability. In a family with hereditary elliptocytosis and an abnormality in spectrin self-association, the membranes had decreased deformability and stability. Finally, membranes from several individuals with Malaysian ovalocytosis had decreased deformability but increased stability. Our data from both pathologic membranes and biochemically perturbed membranes show that deformability and stability change with no fixed relationship to one another. These findings imply that different skeletal protein interactions regulate membrane deformability and stability. In light of these data, we propose a model of the role of skeletal protein interactions in deformability and stability.

Hereditary elliptocytosis due to both qualitative and quantitative defects in membrane skeletal protein 4.1

Blood ◽  
1991 ◽  
Vol 78 (9) ◽  
pp. 2438-2443 ◽  
Author(s):  
JG Conboy ◽  
R Shitamoto ◽  
M Parra ◽  
R Winardi ◽  
A Kabra ◽  
...  
Keyword(s):  
Amino Acids ◽  
Mechanical Stability ◽  
Membrane Skeleton ◽  
Actin Binding ◽  
Erythrocyte Morphology ◽  
Protein 4.1 ◽  
Hereditary Elliptocytosis ◽  
Exon Expression ◽  
Amino Acid Peptide ◽  
Skeletal Protein

Abstract Protein 4.1 is an important structural component of the membrane skeleton that helps determine erythrocyte morphology and membrane mechanical properties. In a previous study we identified a case of human hereditary elliptocytosis (HE) in which decreased membrane mechanical stability was due to deletion of 80 amino acids encompassing the entire 10-Kd spectrin-actin binding domain. A portion of this domain (21 amino acids) is encoded by an alternatively spliced exon that is expressed in late but not early erythroid cells. We now report a case of canine HE in which the abnormal phenotype is caused by failure to express this alternative peptide in the mature red blood cell (RBC) membrane skeleton, in conjunction with quantitative deficiency of protein 4.1. Western blotting of RBC membranes from a dog with HE showed a truncated protein 4.1 that did not react with antibodies directed against the alternative peptide. In addition, sequencing of cloned reticulocyte protein 4.1 cDNA showed a precise deletion of 63 nucleotides comprising this exon. Normal dog reticulocytes did express this exon. Expression of this 21 amino acid peptide during erythroid maturation is therefore essential for proper assembly of a mechanically competent membrane skeleton, because RBCs lacking this peptide have unstable membranes.

scholarly journals Identification of a Novel Role for Dematin in Regulating Red Cell Membrane Function by Modulating Spectrin-Actin Interaction

2012 ◽  
Vol 287 (42) ◽  
pp. 35244-35250 ◽  
Author(s):  
Ichiro Koshino ◽  
Narla Mohandas ◽  
Yuichi Takakuwa
Keyword(s):  
Erythrocyte Membrane ◽  
Quartz Crystal ◽  
Mechanical Stability ◽  
Membrane Skeleton ◽  
Tail Region ◽  
Red Cell Membrane ◽  
Membrane Function ◽  
Pulldown Assay ◽  
Optimal Functioning ◽  
Protein 4.1R

The membrane skeleton plays a central role in maintaining the elasticity and stability of the erythrocyte membrane, two biophysical features critical for optimal functioning and survival of red cells. Many constituent proteins of the membrane skeleton are phosphorylated by various kinases, and phosphorylation of β-spectrin by casein kinase and of protein 4.1R by PKC has been documented to modulate erythrocyte membrane mechanical stability. In this study, we show that activation of endogenous PKA by cAMP decreases membrane mechanical stability and that this effect is mediated primarily by phosphorylation of dematin. Co-sedimentation assay showed that dematin facilitated interaction between spectrin and F-actin, and phosphorylation of dematin by PKA markedly diminished this activity. Quartz crystal microbalance measurement revealed that purified dematin specifically bound the tail region of the spectrin dimer in a saturable manner with a submicromolar affinity. Pulldown assay using recombinant spectrin fragments showed that dematin, but not phospho-dematin, bound to the tail region of the spectrin dimer. These findings imply that dematin contributes to the maintenance of erythrocyte membrane mechanical stability by facilitating spectrin-actin interaction and that phosphorylation of dematin by PKA can modulate these effects. In this study, we have uncovered a novel functional role for dematin in regulating erythrocyte membrane function.

Analytical Solutions for Shear Deformation and Flow of Red Cell Membrane

1984 ◽  
Vol 106 (1) ◽  
pp. 2-9 ◽  
Author(s):  
R. M. Hochmuth ◽  
D. A. Berk
Keyword(s):  
Material Properties ◽  
Deformation Process ◽  
Numerical Solutions ◽  
Functional Dependence ◽  
Geometric Constraints ◽  
Membrane Properties ◽  
Red Cell ◽  
Membrane Material ◽  
Red Cell Membrane ◽  
Closed Form Solutions

Studies of red blood cell deformation have shown that there are a number of membrane material properties that affect the deformation process. In this paper various types of deformation are modeled using geometrical and constitutive simplifications so that the effect of intrinsic elastic and viscous membrane properties and of major geometric constraints is made obvious while other factors are ignored. To this end, numerical solutions are shunned in favor of exact analytical (“closed-form”) solutions to simple and basic membrane deformation problems in order to reveal functional dependence.

Membrane assembly and remodeling during reticulocyte maturation

Blood ◽  
1989 ◽  
Vol 74 (3) ◽  
pp. 1112-1120 ◽  
Author(s):  
JA Chasis ◽  
M Prenant ◽  
A Leung ◽  
N Mohandas
Keyword(s):  
Cell Motility ◽  
Mechanical Stability ◽  
Bone Marrow Cells ◽  
Extrusion Process ◽  
Membrane Properties ◽  
Functional Capability ◽  
Cytoskeletal Remodeling ◽  
Skeletal Protein ◽  
Reticulocyte Maturation ◽  
Erythroid Maturation

Membrane skeletal and cytoskeletal remodeling occurs throughout erythroid maturation. Microtubules and microfilaments have been identified morphologically in the nucleated erythroblast but the functional capability of these cytoskeletal structures during reticulocyte maturation has not been studied. Reticulocytes are formed from orthochromatic normoblasts by the process of nuclear extrusion. Two recognizable stages of reticulocyte maturation follow. The least mature reticulocytes are motile and multilobular, while the more mature reticulocytes are cup-shaped and nonmotile. To study the respective roles of microtubules and microfilaments in nuclear extrusion and cell motility, experiments were performed with agents that perturb these structures. Following the injection into rats of colchicine, a microtubule-disrupting substance, the number of normoblasts arrested at the stage of nuclear extrusion increased linearly over four hours. Similar results were obtained when bone marrow cells were incubated in culture in the presence of colchicine. In contrast, cell motility was dramatically decreased by cytochalasin B, a microfilament-disrupting agent, but not by colchicine. These results imply that microtubules are essential for the nuclear extrusion process, while microfilaments are essential for cell motility. Simultaneous changes in membrane skeletal assembly were assessed by measuring membrane deformability and stability, two properties regulated by the skeletal proteins. In ektacytometric assays, membrane deformability and mechanical stability of immature reticulocytes were markedly decreased to approximately 10% of normal, while that of more mature reticulocytes were nearly normal. Since the skeletal protein organization regulates these membrane properties, our findings imply that substantial membrane skeletal remodeling occurs during reticulocyte maturation. Thus we have identified major remodeling of both skeletal and cytoskeletal components during reticulocyte maturation.

scholarly journals A malaria membrane skeletal protein is essential for normal morphogenesis, motility, and infectivity of sporozoites

2004 ◽  
Vol 167 (3) ◽  
pp. 425-432 ◽  
Author(s):  
Emad I. Khater ◽  
Robert E. Sinden ◽  
Johannes T. Dessens
Keyword(s):  
Cell Shape ◽  
Mechanical Stability ◽  
Membrane Skeleton ◽  
Apicomplexan Parasites ◽  
Membrane Complex ◽  
Skeletal Protein ◽  
Complex Protein ◽  
Parasite Biology ◽  
Inner Membrane Complex ◽  
Membrane Skeletons

Membrane skeletons are structural elements that provide mechanical support to the plasma membrane and define cell shape. Here, we identify and characterize a putative protein component of the membrane skeleton of the malaria parasite. The protein, named PbIMC1a, is the structural orthologue of the Toxoplasma gondii inner membrane complex protein 1 (TgIMC1), a component of the membrane skeleton in tachyzoites. Using targeted gene disruption in the rodent malaria species Plasmodium berghei, we show that PbIMC1a is involved in sporozoite development, is necessary for providing normal sporozoite cell shape and mechanical stability, and is essential for sporozoite infectivity in insect and vertebrate hosts. Knockout of PbIMC1a protein expression reduces, but does not abolish, sporozoite gliding locomotion. We identify a family of proteins related to PbIMC1a in Plasmodium and other apicomplexan parasites. These results provide new functional insight in the role of membrane skeletons in apicomplexan parasite biology.

scholarly journals Hereditary elliptocytosis due to both qualitative and quantitative defects in membrane skeletal protein 4.1

Blood ◽  
1991 ◽  
Vol 78 (9) ◽  
pp. 2438-2443
Author(s):  
JG Conboy ◽  
R Shitamoto ◽  
M Parra ◽  
R Winardi ◽  
A Kabra ◽  
...  
Keyword(s):  
Amino Acids ◽  
Mechanical Stability ◽  
Membrane Skeleton ◽  
Actin Binding ◽  
Erythrocyte Morphology ◽  
Protein 4.1 ◽  
Hereditary Elliptocytosis ◽  
Exon Expression ◽  
Amino Acid Peptide ◽  
Skeletal Protein

Protein 4.1 is an important structural component of the membrane skeleton that helps determine erythrocyte morphology and membrane mechanical properties. In a previous study we identified a case of human hereditary elliptocytosis (HE) in which decreased membrane mechanical stability was due to deletion of 80 amino acids encompassing the entire 10-Kd spectrin-actin binding domain. A portion of this domain (21 amino acids) is encoded by an alternatively spliced exon that is expressed in late but not early erythroid cells. We now report a case of canine HE in which the abnormal phenotype is caused by failure to express this alternative peptide in the mature red blood cell (RBC) membrane skeleton, in conjunction with quantitative deficiency of protein 4.1. Western blotting of RBC membranes from a dog with HE showed a truncated protein 4.1 that did not react with antibodies directed against the alternative peptide. In addition, sequencing of cloned reticulocyte protein 4.1 cDNA showed a precise deletion of 63 nucleotides comprising this exon. Normal dog reticulocytes did express this exon. Expression of this 21 amino acid peptide during erythroid maturation is therefore essential for proper assembly of a mechanically competent membrane skeleton, because RBCs lacking this peptide have unstable membranes.

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