TREP, a novel protein necessary for gliding motility of the malaria sporozoite

Abstract

The invasive stages of parasites of the protozoan phylum Apicomplexa have the capacity to traverse host tissues and invade host cells using a unique type of locomotion called gliding motility. Gliding motility is powered by a sub-membranous actin–myosin motor, and the force generated by the motor is transduced to the parasite surface by transmembrane proteins of the apicomplexan-specific thrombospondin-related anonymous protein (TRAP) family. These proteins possess short cytoplasmic tails that interact with the actin–myosin motor via the glycolytic enzyme aldolase. Gliding motility of the Plasmodium sporozoite, the stage of the malaria parasite that is transmitted by the mosquito to the mammalian host, depends on the TRAP protein. We describe a second protein, herein termed TREP, which also plays a role in the gliding motility of the Plasmodium sporozoite. TREP is a transmembrane protein that possesses a short cytoplasmic tail typical of members of the TRAP family of proteins, as well as a large extracellular region that contains a single thrombospondin type 1 repeat domain. TREP transcripts are expressed predominantly in oocyst stage sporozoites. Plasmodium berghei sporozoites harbouring a disrupted TREP gene have a highly diminished capacity to invade mosquito salivary glands and display a severe defect in gliding motility. We conclude that the gliding motility of the Plasmodium sporozoite in the mosquito depends on at least two proteins, TRAP and TREP.