title: Hereditary spherocytosis of man. Defective cytoskeletal interactions in the erythrocyte membrane.
abstract: Hereditary spherocytosis (HS) is an inherited abnormality of red cell shape and results from defective interactions amongst the components of the cytoskeleton. It is known that spectrin/actin dissociates in low ionic strength media from ghosts and cytoskeletons at a rate which is slower for HS than normal preparations. Hybridization experiments have established that this behaviour is not due to a defective spectrin or actin but resides in a spectrin-binding component of the membrane [Hill, Sawyer, Howlett & Wiley (1981) Biochem. J. 201, 259-266]. In the present study erythrocyte shells have been examined in low ionic strength media and a similar difference in the rate of solubilization has been revealed. Since band 4.1 (but not band 2.1) is a common component of cytoskeletons and shells it is possible that 4.1 may be abnormal in the HS condition. The interaction of band 4.1 with spectrin/actin was examined by low shear falling ball viscometry. The addition of a mixture of band 2.1 and 4.1 to a solution of actin and spectrin tetramer increased the viscosity due to cross-linking of the cytoskeletal elements by band 4.1. When band 2.1/4.1 mixtures were derived from five HS families the viscosity was increased to a greater extent than in the normal controls. This difference was not a result of alterations in the calcium dependence of the spectrin/actin-band 4.1 interaction. The results imply that band 4.1 may be defective in the HS condition.
mesh_terms: D000199:Actins / Q000378:metabolism; D001809:Blood Viscosity / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D046911:Macromolecular Substances; D009994:Osmolar Concentration; D013049:Spectrin / Q000378:metabolism; D013103:Spherocytosis, Hereditary / Q000097:blood*
chemical_list: D000199:Actins; D046911:Macromolecular Substances; D013049:Spectrin; D002118:Calcium