Abstract
An actomyosin motor complex assembled below the parasite's plasma membrane drives erythrocyte invasion by Plasmodium falciparum merozoites. The complex is comprised of several proteins including myosin (MyoA), myosin tail domain interacting protein (MTIP) and glideosome associated proteins (GAP) 45 and 50, and is anchored on the inner membrane complex (IMC), which underlies the plasmalemma. A ternary complex of MyoA, MTIP and GAP45 is formed that then associates with GAP50. We show that full length GAP45 labelled internally with GFP is assembled into the motor complex and transported to the developing IMC in early schizogony, where it accumulates during intracellular development until merozoite release. We show that GAP45 is phosphorylated by calcium dependent protein kinase 1 (CDPK1), and identify the modified serine residues. Replacing these serine residues with alanine or aspartate has no apparent effect on GAP45 assembly into the motor protein complex or its subcellular location in the parasite. The early assembly of the motor complex suggests that it has functions in addition to its role in erythrocyte invasion.
Highlights
Malaria is a disease caused by protozoan parasites of the genus Plasmodium and results in almost a million deaths annually [1]
We chose to introduce the GFP tag at an internal site of GAP45 as previous work in T. gondii revealed that the addition of a YFP tag to the C-terminus of TgGAP45 abrogated its binding to the rest of the motor complex [18] and only an internally located epitope tag was able to circumvent this problem [12]
The localisation of C-GAP45, lacking the N-terminal acylation motifs, resembled very closely that seen for the FL-GAP45: in early schizonts the protein was present in discrete foci (Figure 1C, 33 h) that progress to small ring-like structures as development continues (Figure 1C, 36 h) and in the segmented schizont the protein was evenly distributed around the periphery of each merozoite (Figure 1C, 42 h)
Summary
Malaria is a disease caused by protozoan parasites of the genus Plasmodium and results in almost a million deaths annually [1]. In the asexual cycle in the host’s blood stream the merozoite form of the parasite invades a red blood cell and develops into the so-called trophozoite. DNA replication and mitosis results in a multinucleate syncytium, this undergoes cytokinesis or segmentation to produce new merozoites that are released to invade red blood cells. The IMC may provide shape, rigidity and polarity to the developing merozoites, which bud off from the residual body prior to their release from the red cell. Host cell invasion is an active process powered by an actin-myosin motor complex located between the parasite’s PM and the IMC. Myosin is tethered to the IMC and during invasion moves filamentous (F) actin to the rear of the parasite. The actin filament is coupled to a junction involving the parasite PM and the host cell surface membrane via transmembrane adhesins, the action of the molecular motor results in forward motion of the parasite into the host cell (reviewed in [3,4])
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