Clinical disorders of the red cell membrane skeleton

Abstract

The lipid bilayer of the adult red cell is supported on its inner surface by a complex arrangement of proteins known as the membrane skeleton. This filamentous network, a major component of which is a multifunctional protein called spectrin, has an essential role in determining the shape, structural integrity, and deformability of the red cell. A significant achievement of modern biochemistry and hematology has been the elucidation of the organization of the components of the membrane skeleton and their relationship to other membrane proteins and lipids. This article reviews current concepts of membrane skeleton structure and function and emphasizes recent advances which have been made in characterizing and classifying molecular defects of the skeleton which manifest clinically with changes in the shape and stability of the red cell. The pathobiology of hereditary skeletal defects associated with hereditary spherocytosis (HS), hereditary elliptocytosis (HE), and hereditary pyropoikilocytosis (HPP) are comprehensively discussed. Secondary defects of the membrane skeleton occurring in glucose-6-phosphate dehydrogenase deficiency and sickle cell anemia are also briefly considered.