Red cell membrane skeleton: structure-function relationships.
This papaer reviews our present understanding of ultrastructure, organization, and functional characteristics of the erythrocyte membrane cytoskeleton. This two-dimensional fibrillar network of submembrane proteins can be visualized after extraction of lipids and integral membrane proteins by Triton X-100. Current data suggest that the major structural components of the cytoskeleton are heterodimers of double-stranded spectrin that form tetramers by head-to-head associations. The tetramers may be connected into a fibrillar meshwork by oligomers of actin. The control of membrane integrity by this network is illustrated by examples of two hemolyotic anemias characterized by marked membrane instability and vesiculation: 1) hereditary spherocytic anemia of the house mouse associated with spectrin deficiency and 2) hereditary pyropoikilocytosis, a hemolytic anemia in man characterized by thermal instability of the membrane and the presence of abnormal spectrin, which exhibits an increased propensity to thermal denaturation. Stabilization of the cytoskeletal network by covalent cross-links between the nearest cytoskeletal and integral membrane proteins results in a decrease of membrane deformability and a fixation of erythrocytes in their abnormal shape. Such cross-linkings include: 1) transamidative cross-links produced by introduction of Ca2+ (>0.5 mM) into fresh erythrocytes, and 2) intermolecular disulfide couplings, which are formed after extensive oxidation of fresh erythrocytes or after mild oxidation of ATP-depleted, but not fresh, erythrocytes. The significance of these cross-links in stabilization of shape of abnormal erythrocytes such as schistocytes remains to be determined. We conclude that spectrin and actin form a fibrillar submembrane network that plays an important role in control of membrane integrity, erythrocyte deformability, and stabilization of cells in abnormal shapes.
D000199:Actins; D000745:Anemia, Hemolytic, Congenital / Q000097:blood; D000818:Animals; D001665:Binding Sites; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000276:immunology* / Q000648:ultrastructure; D004912:Erythrocytes / Q000276:immunology*; D004913:Erythrocytes, Abnormal; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D011108:Polymers; D011485:Protein Binding; D013049:Spectrin / Q000172:deficiency
D000199:Actins; D003432:Cross-Linking Reagents; D008565:Membrane Proteins; D011108:Polymers; D013049:Spectrin