Loss-of-function analyses defines vital and redundant functions of thePlasmodiumrhomboid protease family

摘要: Rhomboid-like proteases cleave membrane-anchored proteins within their transmembrane domains. In apicomplexan parasites substrates include molecules that function in parasite motility and host cell invasion. While two Plasmodium rhomboids, ROM1 ROM4, have been examined, the roles of remaining six rhomboids during malaria parasite's life cycle are unknown. We present systematic gene deletion analyses all eight rhomboid-like as a means to discover stage-specific phenotypes potential functions rodent model, P. berghei. Four (ROM4, 6, 7 8) refractory deletion, suggesting an essential role asexual blood stage development. contrast ROM1, 3, 9 10 were dispensable for development exhibited no, subtle or severe defects mosquito liver Parasites lacking ROM9 ROM10 showed no major phenotypic defects. presented delay patency following infection, but previous study had similar growth virulence characteristics wild type parasites. ROM3 mosquitoes readily established oocysts failed produce sporozoites. is first rhomboid identified play vital sporogony.