An essential contractile ring protein controls cell division in Plasmodium falciparum

Rachel M Rudlaff,Stephan Kraemer,Jeffrey D Dvorin,Vincent A Streva

doi:10.1038/s41467-019-10214-z

Rachel M Rudlaff, Stephan Kraemer + Show 2 more

Open Access

https://doi.org/10.1038/s41467-019-10214-z

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Abstract

During the blood stage of human malaria, Plasmodium falciparum parasites divide by schizogony—a process wherein components for several daughter cells are produced within a common cytoplasm and then segmentation, a synchronized cytokinesis, produces individual invasive daughters. The basal complex is hypothesized to be required for segmentation, acting as a contractile ring to establish daughter cell boundaries. Here we identify an essential component of the basal complex which we name PfCINCH. Using three-dimensional reconstructions of parasites at electron microscopy resolution, we show that while parasite organelles form and divide normally, PfCINCH-deficient parasites develop inviable conjoined daughters that contain components for multiple cells. Through biochemical evaluation of the PfCINCH-containing complex, we discover multiple previously undescribed basal complex proteins. Therefore, this work provides genetic evidence that the basal complex is required for precise segmentation and lays the groundwork for a mechanistic understanding of how the parasite contractile ring drives cell division.

Highlights

During the blood stage of human malaria, Plasmodium falciparum parasites divide by schizogony—a process wherein components for several daughter cells are produced within a common cytoplasm and segmentation, a synchronized cytokinesis, produces individual invasive daughters
To confirm that PfCINCH localizes to the basal complex, we co-stained with antibodies directed against PfCINCH and PfMORN1
Parasites deficient in PfCINCH have multiple morphological defects. They form agglomerates that contain the components for several daughter cells within one parasite plasma membrane (PPM)

Summary

Introduction

During the blood stage of human malaria, Plasmodium falciparum parasites divide by schizogony—a process wherein components for several daughter cells are produced within a common cytoplasm and segmentation, a synchronized cytokinesis, produces individual invasive daughters. Despite the importance of this pathogen, many of the biological mechanisms that underlie critical parasite processes remain elusive. In the intraerythrocytic life cycle, the parasite grows and divides inside human red blood cells (RBCs)[6,7,8]. This cycle begins when an invasive merozoite form of the parasite enters a RBC. The parasite replicates its genetic material and organelles over about 44 h to produce components for ~20–32 daughter cells within the common cytoplasm of a schizont. The asexual life cycle culminates after 48 h with egress, the process by which merozoites are rapidly released from the RBC to reinitiate the cycle[10,11,12,13]

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