title: Haemoglobin S and C affect the motion of Maurer's clefts in Plasmodium falciparum-infected erythrocytes.
abstract: The haemoglobinopathies S and C protect carriers from severe Plasmodium falciparum malaria. We have recently shown that haemoglobin S and C interfere with host-actin remodelling in parasitized erythrocytes and the generation of an actin network that seems to be required for vesicular protein trafficking from the Maurer's clefts (a parasite-derived intermediary protein secretory organelle) to the erythrocyte surface. Here we show that the actin network exerts skeletal functions by anchoring the Maurer's clefts within the erythrocyte cytoplasm. Using a customized tracking tool to investigate the motion of single Maurer's clefts, we found that a functional actin network restrains Brownian motion of this organelle. Maurer's clefts moved significantly faster in wild-type erythrocytes treated with the actin depolymerizing agent cytochalasin D and in erythrocytes containing the haemoglobin variants S and C. Our data support the model of an impaired actin network being an underpinning cause of cellular malfunctioning in parasitized erythrocytes containing haemoglobin S or C, and, possibly, for the protective role of these haemoglobin variants against severe malaria.
authors.affiliation: Department of Infectious Diseases, Parasitology, Heidelberg University, Im Neuenheimer Feld 324, 69120, Heidelberg, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Kilian
authors.forename: Martin
authors.initials: M
authors.lastname: Dittmer
authors.forename: Marek
authors.initials: M
authors.lastname: Cyrklaff
authors.forename: Djeneba
authors.initials: D
authors.lastname: Ouermi
authors.forename: Cyrille
authors.initials: C
authors.lastname: Bisseye
authors.forename: Jacques
authors.initials: J
authors.lastname: Simpore
authors.forename: Friedrich
authors.initials: F
authors.lastname: Frischknecht
authors.forename: Cecilia P
authors.initials: CP
authors.lastname: Sanchez
authors.forename: Michael
authors.initials: M
authors.lastname: Lanzer
mesh_terms: D000199:Actins / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology*; D006444:Hemoglobin C / Q000378:metabolism*; D006451:Hemoglobin, Sickle / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D015388:Organelles / Q000378:metabolism* / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000378:metabolism*
chemical_list: D000199:Actins; D006451:Hemoglobin, Sickle; D006444:Hemoglobin C