An essential contractile ring protein controls cell division in Plasmodium falciparum

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.

Fussing About Fission: Defining Variety Among Mainstream and Exotic Apicomplexan Cell Division Modes

“…Although this model has been firmly demonstrated in higher eukaryotes and is defined by proteins in the centrosome's distal and sub-distal appendages (Bornens and Gonczy, 2014), it has not been formally confirmed in the Apicomplexa. The last cycle of S/M-phase, in contrast, is synchronous and coupled to the synchronous budding of the daughters at the end of schizogony (Ferguson et al, 2008;Kono et al, 2016;Rudlaff et al, 2019) (Figures 2A4, 5). Budding follows the activation of the centrosomes' outer-cores, which is always tied to simultaneous centrosome inner-core activation.…”

“…Following plasma membrane docking of the centrosomes, the daughter cytoskeletons start to assemble in connection with the plasma membrane and the buds move outward (Figures 2A4, 5). In P. falciparum the maturation and release of daughters is mediated by CINCH, a contractile protein in the basal complex (Rudlaff et al, 2019).…”

The Riveting Cellular Structures of Apicomplexan Parasites

“…In T. gondii the subpellicular microtubules extend only twothirds of the way down the parasite, hence, completion of budding requires the basal complex. This complex is a contractile ring at the basal end of the IMC, made up of a number of specialized components, including specific alveolins [16,28], myosins [29], and proteins involved in membrane organization such as MORN1 [30]. Several of these components are recruited early in daughter cell formation, forming a ring at the base of extending daughter cells.…”

Fussing about fission: defining variety among mainstream and exotic apicomplexan cell division modes

“…Following plasma membrane docking of the centrosomes, the daughter cytoskeletons start to 339 assemble in connection with the plasma membrane and the buds move outward ( Fig 2A4,5). In 340 P. falciparum the maturation and release of daughters is mediated by CINCH, a contractile 341 protein in the basal complex (Rudlaff et al, 2019). 342 343…”