Control of interaction of spectrin and actin by phosphorylation

Abstract

SPECTRIN is a high molecular weight protein located on the cytoplasmic surface of the mammalian erythrocyte membrane, from which it may be readily liberated by extraction with solutions of low ionic strength. It is thought to be a major structural element of the cell and to play a critical part in maintaining its discoid shape and characteristic viscoelastic properties. Birchmeier and Singer¹ have shown that changes in the shape of red cell ghosts are associated with the phosphorylation of a single serine residue on one of the two spectrin subunits, and have suggested that this might provide a basis for the well-known control of red cell shape by ATP². The erythrocyte membrane also contains actin, which is present in approximately equimolar proportions to the spectrin dimer (molecular weight 500,000 (ref. 3)). We have shown previously⁴ that there is a specific interaction between these two proteins, which reveals itself in the ability of spectrin to provoke the polymerisation of muscle actin in vitro. We show here that this effect depends on the phosphorylation of spectrin. Furthermore, in an undis-persed mixture of spectrin and its cognate actin such phosphorylation causes the formation of a gel. The striking parallel between these results and the previously demonstrated effects of phosphorylation in situ suggests that the shape of the cell is controlled primarily by the actin–spectrin complex.