Evolution and Architecture of the Inner Membrane Complex in Asexual and Sexual Stages of the Malaria Parasite

Abstract

The inner membrane complex (IMC) is a unifying morphological feature of all alveolate organisms. It consists of flattened vesicles underlying the plasma membrane and is interconnected with the cytoskeleton. Depending on the ecological niche of the organisms, the function of the IMC ranges from a fundamental role as reinforcement system to more specialized roles in motility and cytokinesis. In this article, we present a comprehensive evolutionary analysis of IMC components, which exemplifies the adaptive nature of the IMCs' protein composition. Focusing on eight structurally distinct proteins in the most prominent "genus" of the Alveolata-the malaria parasite Plasmodium-we demonstrate that the level of conservation is reflected in phenotypic characteristics, accentuated in differential spatial-temporal patterns of these proteins in the motile stages of the parasite's life cycle. Colocalization studies with the centromere and the spindle apparatus reveal their discriminative biogenesis. We also reveal that the IMC is an essential structural compartment for the development of the sexual stages of Plasmodium, as it seems to drive the morphological changes of the parasite during the long and multistaged process of sexual differentiation. We further found a Plasmodium-specific IMC membrane matrix protein that highlights transversal structures in gametocytes, which could represent a genus-specific structural innovation required by Plasmodium. We conclude that the IMC has an additional role during sexual development supporting morphogenesis of the cell, which in addition to its functions in the asexual stages highlights the multifunctional nature of the IMC in the Plasmodium life cycle.

The Role of Palmitoylation for Protein Recruitment to the Inner Membrane Complex of the Malaria Parasite

“…Gametocytes were produced using a modified version of the established protocol (6,30). For transfection, ring-stage parasites (10%) were electroporated with 100 g of plasmid DNA resuspended in cytomix as described previously (31).…”

“…To circumvent the internal KpnI site in the genes coding PfDHHC3 and PfDHHC9, both open reading frames were cloned into the BamHI/SalI of a derivative of pBcamR (33). This vector mediates the overexpression of mCherry fusion proteins under the control of the ama1 promoter (6). The GFP replacement construct for tagging endogenous PfDHHC1 was designed using pARL-1a-GFP vector.…”

“…Phylogenetic analysis has demonstrated that in addition to a common core set of conserved proteins, the IMC includes many lineage-specific proteins, reflecting additional adaptations to specialized requirements of the compartment within the respective phylogenetic group (6). Functional specialization of IMC proteins is exemplified by a group of well characterized proteins that form the so-called glideosome, the motor complex that drives the locomotion of all motile parasite stages (7)(8)(9).…”

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.…”

ThePlasmodium falciparumblood stages acquire factor H family proteins to evade destruction by human complement

“…Although not motile, the gametocytes of P . falciparum possess an IMC, which here functions to stabilize their crescent shapes (Dearnley et al , 2012; Kono et al , 2012; Simon et al , 2013). The IMC disintegrates during gametogenesis, and then GAP50 relocates from the IMC to the plasmalemma, where it binds FH via CCP5‐7, thus protecting the extracellular gametes from attack by the human complement (Simon et al , 2013).…”