title: Host cell invasion by the apicomplexans: the significance of microneme protein proteolysis.
abstract: Intracellular life-style has been adopted by many pathogens as a successful immune evasion mechanism. To gain entry to a large variety of host cells and to establish an intracellular niche, Toxoplasma gondii and other apicomplexans rely on an active process distinct from phagocytosis. Calcium-regulated secretion of microneme proteins and parasite actin polymerization together with the action of at least one myosin motor act in concert to generate the gliding motility necessary to propel the parasite into host cells. During this active penetration, host cell transmembrane proteins are excluded from the forming parasitophorous vacuole hence conferring the resistance to acidification and degradative fusion. Apicomplexans possess a large repertoire of microneme proteins that contribute to invasion, but their precise role and the level of functional redundancy remain to be evaluated. Remarkably, most microneme proteins are proteolytically cleaved during biogenesis and post-exocytosis. The significance of the processing events and the identification of the proteases implicated are the object of intensive investigations. These proteases may constitute potential drug targets for intervention against malaria and other diseases caused by these parasites.
authors.affiliation: Department of Biological Sciences, Imperial College London, Sir Alexander Fleming Building, South Kensington Campus, London SW7 2AZ, UK.
authors.forename: Timothy
authors.initials: T
authors.lastname: Dowse
authors.forename: Dominique
authors.initials: D
authors.lastname: Soldati
mesh_terms: D000818:Animals; D016782:Apicomplexa / Q000472:pathogenicity*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*; D015800:Protozoan Proteins / Q000378:metabolism*; D014122:Toxoplasma / Q000472:pathogenicity; D014123:Toxoplasmosis / Q000469:parasitology
chemical_list: D015815:Cell Adhesion Molecules; D015800:Protozoan Proteins; D010447:Peptide Hydrolases