Origin, composition, organization and function of the inner membrane complex of Plasmodium falciparum gametocytes

Abstract

SummaryThe most virulent of the human malaria parasites, Plasmodium falciparum, undergoes a remarkable morphological transformation as it prepares itself for sexual reproduction and transmission via mosquitoes. Indeed P. falciparum is named for the unique falciform or crescent shape of the mature sexual stages. Once the metamorphosis is completed, the mature gametocyte releases from sequestration sites and enters the circulation, thus making it accessible to feeding mosquitoes. Early ultrastructural studies showed that gametocyte elongation is driven by the assembly of a system of flattened cisternal membrane compartments underneath the parasite plasma membrane and a supporting network of microtubules. Here we describe the molecular composition and origin of the sub-pellicular membrane complex, and show that it is analogous to the inner membrane complex, an organelle with structural and motor functions that is well conserved across the apicomplexa. We identify novel crosslinking elements that might help stabilize the inner membrane complex during gametocyte development. We show that changes in gametocyte morphology are associated with an increase in cellular deformability and postulate that this enables the gametocytes to circulate in the bloodstream without being detected and removed by the mechanical filtering mechanisms in the spleen of the host.

Mitochondrial ATP synthase is dispensable in blood-stage Plasmodium berghei rodent malaria but essential in the mosquito phase

“…Material was stained en bloc with 2% uranyl acetate and Walton's lead aspartate for maximum membrane contrast as described (55) before embedding in Durcupan Araldite embedding resin. Gametocytes were distinguished from asexual parasites by the presence of an inner membrane complex in the parasites (34).…”

“…After 22 h, we stained with an antiPbs28 antibody, a protein specific for activated females, zygotes, and ookinetes ( Fig. 5A) (34). These developmental stages were subsequently counted and compared with a P. berghei ANKA WT control (Fig.…”

The development of malaria parasites in the mosquito midgut

“…Gametocytes possess an inner membrane complex (IMC) underneath their plasmalemma, which consists of flat membranous sacs, the alveoli, and supporting structural elements and which is thought to be required for the stability of the crescent‐shaped parasite stages (Dearnley et al ., 2012; Kono et al ., 2012; Simon et al ., 2013; reviewed in Harding and Meissner, 2014; Boucher and Bosch, 2015). During gametogenesis, the IMC disintegrates, resulting in gametes solely confined by the plasmalemma.…”

Biology of Malaria Transmission

“…Products of multigene families involved in host cell modifications, such as STEVOR and RIFIN, are expressed during gametocyte development (McRobert et al 2004;Petter et al 2008), but their functional role in gametocytogenesis or cytoadherence has not been shown. Nevertheless, a switch in deformability of mature gametocytes (Aingaran et al 2012;Dearnley et al 2012;Tiburcio et al 2012) is accompanied by reorganization of STEVOR in the RBC membrane of mature gametocytes . Taken together, the sequestration and subsequent development of immature gametocytes in the bone marrow and spleen is likely to be maintained through mechanical retention and as yet uncharacterized binding properties, whereas the switch in deformability at the mature stage V gametocyte stage may facilitate their release from sequestration sites into the periphery.…”