A malaria protein essential for blood and transmission-stages of parasites identified!

A malaria protein essential for blood and transmission-stages of parasites identified!


Plasmodium spp. infections cause ~200 million cases of malaria and 500,000 deaths annually, with the most severe forms caused by Plasmodium falciparum. The complete parasite life cycle requires both the mosquito and human hosts.

Clinical malaria results from asexual proliferation of parasites in human red blood cells. These blood-stage parasites replicate via schizogony, wherein repeated nuclear divisions produce a multi-nucleated cell. Individual nuclei and associated organelles are partitioned to produce daughter parasites during a specialized cytokinesis known segmentation, which is divergent from cellular division in the human host. Because the process of cellular division is so different from human cells, an understanding of its molecular mechanism could reveal vulnerable targets for anti-malarials.

The inner membrane complex (IMC), a specialized structure within the parasite composed of parasite proteins and a double lipid bilayer that is closely associated with the plasma membrane, is hypothesized to orchestrate parasite assembly and division.

In addition to its role in parasite division, the IMC plays a critical role in cellular architecture and gliding motility. Two Rab-GTPases, Rab11a and Rab11b, are known to contribute to vesicular transport that is important for IMC formation, but other factors that regulate IMC biogenesis remain largely unknown.

During the blood-stage of human malaria, a subset of parasites differentiates into transmission forms, known as gametocytes, which are ingested during a mosquito blood meal. The IMC is central to the architecture of the developing gametocyte as well. Parasite proteins important for regulation and biogenesis of the gametocyte IMC are also largely unknown in P. falciparum. A deeper understanding of the mechanism of blood-stage parasite division with particular focus on IMC formation will facilitate the discovery of novel anti-malarial therapeutics.

Researchers in the journal Nature Communications show that PF3D7_0917000, which they named P. falciparum merozoite organizing protein (PfMOP), is essential for the biogenesis of the IMC in both asexual and sexual parasites.

Following PfMOP knockdown, blood-stage parasites undergo incomplete segmentation resulting in a residual agglomerate of partially divided cells. While parasite organelles develop normally, the IMC fails to form in this agglomerate.

The IMC defect is more severe in the long-lived transmission stage where aberrant formation of the IMC in PfMOP-deficient gametocytes causes maturation arrest and death.

These results show that PfMOP, through its regulation of IMC formation, is critical for the cellular architecture of both blood and transmission stages of human malaria.