Irreversibly sickled cell β-actin: Defective filament formation

Abstract

It has been demonstrated that cysteine modification in irreversibly sickled cell β-actin slows down the remodeling of membrane skeletons [Shartava et al.: J Cell Bio 128:805812, 1995]. This slow remodeling can be due to alterations in spectrin-actin binding and/or actin-actin interactions in irreversibly sickled cell (ISC) membrane skeletons. In these studies we demonstrate that ISC actin binds spectrin normally. However, ISC β-actin polymerizes and depolymerizes more slowly than control β-actin, and forms unusual aggregates when placed under polymerizing conditions. Electron microscopic analysis of actin polymers indicated that ISC actin generates a large amount of aggregates which we conclude ere due to the structural modification caused by the disulfide bridge between cysteine284 and cysteine373 in β-actin.