PIEZO1 E756del gain of function mutation makes human erythrocytes less habitable for malaria parasites

Abstract

PIEZO1 is a mechanoreceptor cation channel that regulates erythrocyte volume and, as a consequence, modulates cell density. In humans, some PIEZO1 gain of function (GoF) variants are associated with a disease called hereditary xerocytosis, characterized by increased erythrocyte density, shape distortion and compensated hemolytic anemia. E765del is a prevalent GoF PIEZO1 mutation and carriers of this mutation have variable protection from severe malaria. Mice with the same mutation have a lower rate of parasite replication and delayed death in a rodent malaria model.