Neuroacanthocytosis-related changes in erythrocyte membrane organization and function

The presence of thorny erythrocytes in patients with mutations in chorein, XK protein, and junctophilin-3 suggests that abnormalities in the organization of the erythrocyte membrane are related to the neurodegeneration process. Band 3, the major erythrocyte membrane protein, is at the center of a multiprotein complex that regulates erythrocyte metabolism, erythrocyte shape, and erythrocyte survival. Immunoblot analyses indicate that alterations in band 3 structure are involved in the formation of acanthocytes, probably through phosphorylation-regulated interaction with the cytoskeleton components beta spectrin, actin and p55. In addition, preliminary data from a proteomic analysis suggest the occurrence of neuroacanthocytosis-related changes in the association of various classes of cytosolic proteins with the membrane. The relationship between these observations and the altered vesicle formation in vitro is not clear, but together these findings suggest an inborn flaw in the membrane organization of erythrocytes and possibly neurons. These data provide a foundation for further research on the identity of the mechanism of acanthocyte formation, which may be a first step towards intervention in the neurodegenerative process.