Mode of action of myosin motors in Apicomplexa parasites (Funktionsweise des Aktinomyosinmotors von Apicomplexen Parasiten)

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Protozoan parasites of the phylum Apicomplexa are of enormous medical and veterinary significance, being responsible for a wide variety of diseases including malaria, toxoplasmosis, coccidiosis, cryptosporidiosis, theileriosis and babesiosis. Successful attachment and invasion of the host cells are key to the survival of these obligate intracellular parasites. Toxoplasma gondii, the most ubiquitous of the Apicomplexan, has developed a remarkable ability to actively penetrate any nucleated cells from virtually all warm blooded animals. The mechanisms responsible for this exceptional success in invasion are not elucidated yet at the molecular level. Like other Apicomplexan, T. gondii lacks cilia or flagella for locomotion but harbors an unusual form of gliding motility which is essential for host cell invasion. The basic engine for gliding locomotion is the actin cytoskeleton and likely involves a myosin to generate the mechanochemical force along the actin filaments. All myosins identified so far in Apicomplexa are very unconventional and constitute a novel phylogenetic and structural class of myosins (XIV). The main goal of this research proposal is to characterize the myosin(s) involved in the gliding motility of Apicomplexan parasites and to determine their mode of action. To achieve this goal we will combine in vitro and in vivo studies to elucidate their structure/function relationships.