Dynamics of detergent-resistant membranes of Plasmodium falciparum during blood stage development

Membrane microdomains, also known as detergent-resistant membranes (DRMs), are tightly packed assemblies enriched in cholesterol and sphingolipids, where various membrane-associated processes occur. Many intracellular pathogens, including Plasmodium, exploit these raft-like structures to recognize and invade host cells. In particular, Plasmodium depends on host cholesterol to build its own membranes, as it is unable to perform sterol synthesis. Using quantitative proteomics, lipid analysis, and bioinformatics, this study defines the composition and dynamics of Plasmodium falciparum DRMs from key developmental stages: schizonts, which give rise to invasive merozoites, and gametocytes, which are responsible for transmission to the mosquito vector. Comparative analysis of the flotation properties of DRM-associated proteins and lipids reveals both conserved and stage-specific features in the structural organization of membrane microdomains. Following parasite invasion, host DRMs are also remodeled with the internalization of components of the erythrocyte junctional complex and their repositioning in the newly generated parasitophorous vacuole membrane. Prediction and analysis of the DRM interactomes reveals a core of proteins involved in fundamental biological processes maintained between the schizont and gametocyte stages. This common core forms a highly interconnected subnetwork that occupies a central position in the interactomes, while stage-specific functions occupy a peripheral position in the network.