Malaria And Molecular Defects In The Red Blood Cell Skeleton

The spectrin-based skeleton is a complex spectrin-actin network located at the inner surface of the erythrocyte membrane. This network is responsible for the shape and dynamic properties of red blood cells as clearly demonstrated by numerous mutations of its main components (particularly spectrin) associated with hereditary haemolytic anaemia, such as hereditary elliptocytosis. Prospective epidemiological studies have revealed a higher prevalence of hereditary elliptocytosis in West Africa than in Caucasian populations. Molecular studies have shown the prevalence of elliptocytosis cases related to particular spectrin mutations. These studies have also revealed the frequency of several a-spectrin polymorphisms. Malaria represents one of the most important selective factors affecting human populations and leading to the persistence of several inherited diseases of red blood cells. These observations raise the question of the selection of novel malaria-resistant genes. Culture of Plasmodium falciparum in red blood cells bearing elliptocytogenic alleles of spectrin showed that these alleles are additional genetic factors of malaria resistance in vitro. As an increasing number of direct interactions between the parasite proteins and the spectrin-based skeleton are characterized, the relationships between parasite ligands and particular spectrin domains should be examined more closely.