Essential function of alveolin Pf IMC1g in the Plasmodium falciparum asexual blood stage

Abstract

ABSTRACT The cytoskeleton of Plasmodium parasites is essential for replication, motility, and infectivity. Plasmodium falciparum leverages a family of cytoskeletal proteins known as alveolins to meet these diverse needs. The functional role of individual alveolins in Plasmodium blood stages, however, remains unexplored. Here, we demonstrate that the alveolin Pf IMC1g (PF3D7_0525800) is essential for P. falciparum asexual replication. Unlike alveolins studied in mosquito stages, Pf IMC1g does not play an important role in determining cell shape. Pf IMC1g-deficient parasites exhibit only minor defects during segmentation, with most merozoites being indistinguishable from wild type by super-resolution fluorescence microscopy, ultrastructure expansion microscopy, and electron microscopy. In the current study, we demonstrate that the absence of Pf IMC1g leads to parasite death shortly after merozoite internalization into red blood cells (RBCs). Pf IMC1g-deficient parasites egress and enter new RBCs but fail to develop into rings and die. We hypothesize that the primary role of Pf IMC1g is to maintain structural integrity, protecting parasites from incurring damage during the process of internalization. Along with the dispensability of Pf IMC1g for merozoite cell shape, we report new findings about the architecture of Plasmodium alveolins including the localization of Pf IMC1e and 1f to the basal complex. Importance Infection by the Plasmodium falciparum parasite is responsible for the most severe form of human malaria. The asexual blood stage of the parasite, which occurs inside human red blood cells, is responsible for the symptoms of malaria and is the target of most antimalarial drugs. Plasmodium spp. rely on their highly divergent cytoskeletal structures to scaffold their cell division, sustain the mechanical stress of invasion, and survive in both the human bloodstream and the mosquito. We investigate the function of a class of divergent intermediate filament-like proteins called alveolins in the clinically important blood stage. The functional role of individual alveolins in Plasmodium remains poorly understood due to pleiotropic effects of gene knockouts and redundancy among alveolins. We evaluate the localization and essentiality of the four asexual-stage alveolins and find that Pf IMC1g and Pf IMC1c are essential. Furthermore, we demonstrate that Pf IMC1g is critical for survival of the parasite post-invasion.