Abstract
Malaria parasites possess unique subcellular structures and organelles. One of these is the crystalloid, a multivesicular organelle that forms during the parasite’s development in vector mosquitoes. The formation and function of these organelles remain poorly understood. A family of six conserved and modular proteins named LCCL-lectin adhesive-like proteins (LAPs), which have essential roles in sporozoite transmission, localise to the crystalloids. In this study we analyse crystalloid formation using transgenic Plasmodium berghei parasites expressing GFP-tagged LAP3. We show that deletion of the LCCL domain from LAP3 causes retarded crystalloid development, while knockout of LAP3 prevents formation of the organelle. Our data reveal that the process of crystalloid formation involves active relocation of endoplasmic reticulum-derived vesicles to common assembly points via microtubule-dependent transport. Inhibition of microtubule-dependent cargo transport disrupts this process and replicates the LCCL domain deletion mutant phenotype in wildtype parasites. These findings provide the first clear insight into crystalloid biogenesis, demonstrating a fundamental role for the LAP family in this process, and identifying the crystalloid and its formation as potential targets for malaria transmission control.
Highlights
Reducing parasite transmission by mosquitoes is an essential part of successful malaria control and eradication programmes
Ookinete cultures were set up from gametocytemic mouse blood and crystalloid formation was assessed at different times post-gametogenesis
The first clear signs of ookinete development were visible at 5 h, with the spherical zygotes displaying a short protrusion corresponding to the apical end of the ookinete (Fig. 1A)
Summary
Reducing parasite transmission by mosquitoes is an essential part of successful malaria control and eradication programmes. There is strong evidence that the Plasmodium LAPs are involved in sporozoite transmission: knockout of five of the family members in Plasmodium berghei, either as single or double knockouts, gives rise to arrested sporozoite development in the oocyst and subsequent failure of the parasite to be transmitted by mosquito bite (Claudianos et al, 2002; Raine et al, 2007; Carter et al, 2008; Ecker et al, 2008; Lavazec et al, 2009). The biological significance of these findings with respect to LAP function in apicomplexan parasites is discussed
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