The dynamin-related protein Dyn2 is essential for both apicoplast and mitochondrial fission in Plasmodium falciparum.

Dynamins, or dynamin-related proteins (DRPs), are large mechano-sensitive GTPases mediating membrane dynamics or organellar fission/fusion events. Plasmodium falciparum encodes three dynamin-like proteins whose functions are poorly understood. Here, we demonstrate that PfDyn2 mediates both apicoplast and mitochondrial fission. Using super-resolution and ultrastructure expansion microscopy, we show that PfDyn2 is expressed in the schizont stage and localizes to both the apicoplast and mitochondria. Super-resolution long-term live cell microscopy shows that PfDyn2-deficient parasites cannot complete cytokinesis because the apicoplast and mitochondria do not undergo fission. Further, the basal complex or cytokinetic ring in Plasmodium cannot fully contract upon PfDyn2 depletion, a phenotype secondary to physical blockage of undivided organelles in the middle of the ring. Our data suggest that organellar fission defects result in aberrant schizogony, generating unsuccessful merozoites. The unique biology of PfDyn2, mediating both apicoplast and mitochondrial fission, has not been observed in other organisms possessing two endosymbiotic organelles. Highlights: PfDyn2 is essential for schizont-stage development.PfDyn2 mediates both apicoplast and mitochondrial fission.Deficiency of PfDyn2 leads to organellar fission failures and blockage of basal complex contraction.Addition of apicoplast-derived metabolite IPP does not rescue the growth defects.

A PPP-type pseudophosphatase is required for the maintenance of basal complex integrity in Plasmodium falciparum.

During its asexual blood stage, P. falciparum replicates via schizogony, wherein dozens of daughter cells are formed within a single parent. The basal complex, a contractile ring that separates daughter cells, is critical for schizogony. In this study, we identify a Plasmodium basal complex protein essential for basal complex maintenance. Using multiple microscopy techniques, we demonstrate that PfPPP8 is required for uniform basal complex expansion and maintenance of its integrity. We characterize PfPPP8 as the founding member of a novel family of pseudophosphatases with homologs in other Apicomplexan parasites. By co-immunoprecipitation, we identify two additional new basal complex proteins. We characterize the unique temporal localizations of these new basal complex proteins (late-arriving) and of PfPPP8 (early-departing). In this work, we identify a novel basal complex protein, determine its specific role in segmentation, identify a new pseudophosphatase family, and establish that the P. falciparum basal complex is a dynamic structure.

Identification of basal complex protein that is essential for maturation of transmission-stage malaria parasites.

Malaria remains a global driver of morbidity and mortality. To generate new antimalarials, one must elucidate the fundamental cell biology of Plasmodium falciparum, the parasite responsible for the deadliest cases of malaria. A membranous and proteinaceous scaffold called the inner membrane complex (IMC) supports the parasite during morphological changes, including segmentation of daughter cells during asexual replication and formation of transmission-stage gametocytes. The basal complex lines the edge of the IMC during segmentation and likely facilitates IMC expansion. It is unknown, however, what drives IMC expansion during gametocytogenesis. We describe the discovery of a basal complex protein, PfBLEB, which we find to be essential for gametocytogenesis. Parasites lacking PfBLEB harbor defects in IMC expansion and are unable to form mature gametocytes. This article demonstrates a role for a basal complex protein outside of asexual division, and, importantly, highlights a potential molecular target for the ablation of malaria transmission.

The Ringleaders: Understanding the Apicomplexan Basal Complex Through Comparison to Established Contractile Ring Systems.

The actomyosin contractile ring is a key feature of eukaryotic cytokinesis, conserved across many eukaryotic kingdoms. Recent research into the cell biology of the divergent eukaryotic clade Apicomplexa has revealed a contractile ring structure required for asexual division in the medically relevant genera Toxoplasma and Plasmodium; however, the structure of the contractile ring, known as the basal complex in these parasites, remains poorly characterized and in the absence of a myosin II homolog, it is unclear how the force required of a cytokinetic contractile ring is generated. Here, we review the literature on the basal complex in Apicomplexans, summarizing what is known about its formation and function, and attempt to provide possible answers to this question and suggest new avenues of study by comparing the Apicomplexan basal complex to well-studied, established cytokinetic contractile rings and their mechanisms in organisms such as S. cerevisiae and D. melanogaster. We also compare the basal complex to structures formed during mitochondrial and plastid division and cytokinetic mechanisms of organisms beyond the Opisthokonts, considering Apicomplexan diversity and divergence.