Phosphoinositide metabolism and shape control in sheep red blood cells

Metabolic depletion of sheep red blood cells leads to decreased intracellular concentrations of ATP and reduced glutathione as well as degradation of phosphoinositides. In sheep red blood cells, depletion of ATP induced two types of shape transformation: one early phase involving formation of protrusions on the cell surface similar to those observed upon depletion of human red blood cells; and one late phase, in which the sheep red blood cells develop long, rod-shaped projections. During the initial stages of shape changes, degradation of the phosphoinositides parallels the discocyte-echinocyte transformation, thus giving further support to a shape-controlling mechanism based on the bilayer-couple hypothesis. However, formation of the long projections does not coincide with turnover of the phosphoinositides but rather with the level of reduced glutathione. This indicates that development of these rod-like extensions on the cell surface is induced by oxidative processes that may well involve cross-linking of membrane skeleton proteins.