Hematopoietic Protein-1 Regulates the Actin Membrane Skeleton and Membrane Stability in Murine Erythrocytes
Figure 7
Model of the erythrocyte membrane cytoskeleton in wildtype and Hem-1 null mice.
(top) The red cell membrane in WT mice consists of a lipid bilayer embedded with two main complexes of structural proteins: The ankyrin complex and the junctional complex (also known as the 4.1R complex), which are connected by horizontal flexible helices of α- and β- spectrin heterodimers and tetramers. Stability of the complexes is regulated in part by phosphorylation of adducin (on Serine 724 in mice) by protein kinase C (PKC), which leads to decreased F-actin capping and dissociation of spectrin from actin. Since PKC-mediated serine phosphorylation is typically opposed by protein phosphatase 2A (PP2A), we propose that PP2A dephosphorylates adducin. PP2A, PKC (bottom), and Hem-1 (top) have all been shown to associate with Rac1. Loss of Hem-1 results in decreased PP2a regulatory subunit B (PP2Ar) and structural subunit A protein expression and increased PKC-mediated phosphorylation of Ser724 on adducin (bottom). Phospho-adducin is then degraded, resulting in the dissociation of spectrin from actin and decreased stability of junctional complex proteins and the membrane cytoskeleton. GPA (Glycophorin A), GPC (Glycophorin C), PP2Ac (protein phosphatase 2A catalytic subunit), PP2Ar (protein phosphatase 2A regulatory subunit).