Vesicle dynamics during the egress of malaria gametocytes from the red blood cell

Malaria parasites are obligate intracellular pathogens that live in human red blood cells harbored by a parasitophorous vacuole. The parasites need to exit from the red blood cell to continue life-cycle progression and ensure human-to-mosquito transmission. Two types of blood stages are able to lyse the enveloping red blood cell to mediate egress, the merozoites and the gametocytes. The intraerythrocytic parasites exit the red blood cell via an inside-out mode during which the membrane of the parasitophorous vacuole ruptures prior to the red blood cell membrane. Membrane rupture is initiated by the exocytosis of specialized secretory vesicles following the perception of egress triggers. The molecular mechanisms of red blood cell egress have particularly been studied in malaria gametocytes. Upon activation by external factors, gametocytes successively discharge at least two types of vesicles, the osmiophilic bodies needed to rupture the parasitophorous vacuole membrane and recently identified egress vesicles that are important for the perforation of the erythrocyte membrane. In recent years, important components of the signaling cascades leading to red blood cell egress have been investigated and several proteins of the osmiophilic bodies have been identified. We here report on the newest findings on the egress of gametocytes from the red blood cell. We further focus on the content and function of the egress-related vesicles and discuss the molecular machinery that might drive vesicle discharge.