Research Focus
Erythrocyte exit: Out, damned merozoite! Out I say!

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A new study has combined video microscopy with fluorescent labeling of host and parasite membranes to follow Plasmodium falciparum merozoites as they exit their host erythrocyte. The result has yielded some arresting images, which make compelling viewing irrespective of whether or not you have an interest in cell motility in general or P. falciparum erythrocyte exit in particular. Moreover, this work injects important new insights into the long-running debate about the biological mechanisms that underpin merozoite release.

Section snippets

Merozoite release: many models, little consensus

Newly developed Plasmodium merozoites are physically prevented from invading fresh erythrocytes by two membranes: the plasma membrane of their host erythrocyte and the parasitophorous vacuole membrane that encloses them within that erythrocyte. More than 50 years ago, Bill Trager observed Plasmodium lophurae merozoites being ‘ejected in a seething motion’ from infected duck erythrocytes 1, 2, a choice of language that serves both to describe beautifully the movies that accompany a new paper

Merozoite release in real-time: deadly flowers

Perhaps the single most-important insight in the new work is the warning it brings to be mindful of the ‘observer effect’. Just as a green fluorescence protein (GFP)-tagged protein moves to different locations in the cell depending on where the researcher places the GFP tag relative to a targeting motif [9], and Schrödinger's famous conceptual cat may be both alive and dead if enclosed in a box that no researcher can see into, so it appears that P. falciparum parasites may behave very

Are Plasmodium merozoites a special case?

The facet of these movies that make them such compelling viewing – the explosive and almost malevolent dispersal of merozoites in a ‘seething motion’ – serves to reinforce what might be an important difference between Plasmodium merozoites and other apicomplexan zoite stages. Host cell exit in Toxoplasma gondii appears to require the active participation of the actin–myosin motor complex that also powers host cell invasion, and elegant in vitro experiments have shown that the signal for

The molecular details are yet to be filled in

So how is the force generated that expels merozoites from their host erythrocyte? Glushakova et al. [3] treated synchronized P. falciparum cultures with a variety of positive-curvature amphiphiles, a class of compounds that incorporate into membranes and reduce the energy barrier for membrane rupture by promoting membrane curvature. The addition of sub-hemolytic concentrations of amphiphiles that incorporate into either the inner or outer leaflet of membranes all resulted in an increase in

Acknowledgements

Thanks to Matthew Jones, Stephen Jordan and Lindsay Parish for constructive discussions.

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