IRREVERSIBLY SICKLED CELL BETA-ACTIN - DEFECTIVE FILAMENT FORMATION

It has been demonstrated that cysteine modification in irreversibly si ckled cell beta-actin slows down the remodeling of membrane skeletons [Shartava et al.: J Cell Biol 128:805-812, 1995]. This slow remodeling can be due to alterations in spectrin-actin binding and/or actin-acti n interactions in irreversibly sickled cell (ISC) membrane skeletons, In these studies we demonstrate that ISC actin binds spectrin normally . However, ISC beta-actin polymerizes and depolymerizes more slowly th an control beta-actin, and forms unusual aggregates when placed under polymerizing conditions. Electron microscopic analysis of actin polyme rs indicated that ISC actin generates a large amount of aggregates whi ch we conclude are due to the structural modification caused by the di sulfide bridge between cysteine(284) and cysteine(373) in beta-actin. (C) 1997 Wiley-Liss, Inc.