PLASMODIUM-FALCIPARUM - INFLUENCE OF MALARIAL AND HOST ERYTHROCYTE SKELETAL PROTEIN INTERACTIONS ON PHOSPHORYLATION IN INFECTED ERYTHROCYTES

Phosphorylation of components of the erythrocyte membrane skeleton has major effects on the physical properties of the membrane. Infection o f red cells by the protozoan parasite Plasmodium falciparum leads to a marked increase in the level of phosphorylation of red cell protein 4 .1 and the insertion into the red cell skeleton of parasite-encoded ph osphoproteins, including the mature-parasite-infected erythrocyte surf ace antigen (MESA). Because of the tight association of MESA with prot ein 4.1, we set out to determine the importance of this interaction an d that of other parasite-encoded skeletal-associated proteins to phosp horylation of the infected red cell membrane. Our results show that ne ither MESA nor protein 4.1 is required for phosphorylation of its bind ing partner. Further, phosphorylation of MESA and protein 4.1 occurs i ndependently of the presence of knobs, the expression of PfHRP1, or cy toadherence phenotype. In contrast to previous studies, we were unable to detect a change in the molecular weight of protein 4.1 in erythroc ytes infected with cytoadherent parasite lines. In red cells infected with parasites expressing PfHRP1 (K+), MESA and protein 4.1 are substr ates for a kinase with the inhibitor profile of a casein kinase. Surpr isingly, however, when we examined phosphorylation of MESA and protein 4.1 in K--infected erythrocytes, we found that casein kinase I and II inhibitors had no, or greatly reduced, effectiveness, and in fact, ph osphorylation of these two proteins was enhanced in some instances. (C ) 1998 Academic Press.