Invovled in Hereditiary spherocytosis -
the pathogenic mutations of HS affect ankyrin,band3,spectrin,or band 4.2. Hereditary spherocytosis is caused by abnormalities in the membrane skeleton, a network of proteins that underlies lipid bilayer of the red cell (Fig. 11-1). The major membrane skeleton protein is spectrin, a long, flexible het- erodimer that self-associates at one end and binds sho actin filaments at its other end. These contacts create a two- dimensional meshwork that is linked to the overlying mem- brane through ankyrin and band 4.2 to the intrinsic membrane protein called band 3, and through band 4.1 to glycophorin. The mutations in hereditary spherocytosis most frequently involve ankyrin, band 3, and spectrin, but mutations in other components of the skeleton have also been described.A shared feature of the pathogenic mutations is that they weaken the veical interactions between the membrane skeleton and the intrinsic membrane proteins. This defect somehow destabilizes the lipid bilayer of the red cells, which shed membrane vesicles into the cir- culation as they age. Little cytoplasm is lost in the process and as a result the surface area to volume ratio decreases progressively over time until the cells become spherical (Fig. 11-1). The spleen plays a major role in the destruction of sphe- rocytes. Red cells must undergo extreme degrees of defor- mation to pass through the splenic cords. The floppy discoid shape of normal red cells allows considerable latitude for shape changes. By contrast, spherocytes have limited deform- ability and are sequestered in the splenic cords, where they are destroyed by the plentiful resident macrophages. The critical role of the spleen is illustrated by the beneficial effect of splenectomy; although the red cell defect and spherocytes persist, the anemia is corrected. Ref: Robbins 9/,e pg:633
Troponin
Ankyrin
Pyrin
Actin
Haematology