4.4 Article

Plasmodium falciparum coronin organizes arrays of parallel actin filaments potentially guiding directional motility in invasive malaria parasites

Journal

MALARIA JOURNAL
Volume 14, Issue -, Pages -

Publisher

BIOMED CENTRAL LTD
DOI: 10.1186/s12936-015-0801-5

Keywords

Gliding motility; Coronin; Actin; Plasmodium; Tight junction; Merozoite

Funding

  1. National Health and Medical Research Council of Australia (NHMRC) Project Grant [APP1024678]
  2. Human Frontier Science Program (HFSP) Young Investigator Program Grant [RGY0071/2011]
  3. Australian Research Council (ARC) Discovery Project Grant [DP1094497]
  4. European Union FP7 network of excellence EVIMalaR
  5. Pratt Foundation postgraduate scholarship through the University of Melbourne
  6. NHMRC Dora Lush Scholarships [APP1018002, APP1055246]
  7. University of Melbourne Overseas Research Experience Scholarship
  8. Australian Society of Parasitology JD Smyth Postgraduate Travel Award
  9. Australian Society for Biochemistry and Molecular Biology
  10. Early Career Fellowship from the NHMRC [APP1053801]
  11. Chica and Heinz Schaller foundation
  12. Future Fellowship from the ARC [FT100100112]
  13. Wellcome Trust [100993/Z/13/Z]
  14. Australian Research Council [DP1094497] Funding Source: Australian Research Council

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Background: Gliding motility in Plasmodium parasites, the aetiological agents of malaria disease, is mediated by an actomyosin motor anchored in the outer pellicle of the motile cell. Effective motility is dependent on a parasite myosin motor and turnover of dynamic parasite actin filaments. To date, however, the basis for directional motility is not known. Whilst myosin is very likely orientated as a result of its anchorage within the parasite, how actin filaments are orientated to facilitate directional force generation remains unexplained. In addition, recent evidence has questioned the linkage between actin filaments and secreted surface antigens leaving the way by which motor force is transmitted to the extracellular milieu unknown. Malaria parasites possess a markedly reduced repertoire of actin regulators, among which few are predicted to interact with filamentous (F)-actin directly. One of these, PF3D7_1251200, shows strong homology to the coronin family of actin-filament binding proteins, herein referred to as PfCoronin. Methods: Here the N terminal beta propeller domain of PfCoronin (PfCor-N) was expressed to assess its ability to bind and bundle pre-formed actin filaments by sedimentation assay, total internal reflection fluorescence (TIRF) microscopy and confocal imaging as well as to explore its ability to bind phospholipids. In parallel a tagged PfCoronin line in Plasmodium falciparum was generated to determine the cellular localization of the protein during asexual parasite development and blood-stage merozoite invasion. Results: A combination of biochemical approaches demonstrated that the N-terminal beta-propeller domain of PfCoronin is capable of binding F-actin and facilitating formation of parallel filament bundles. In parasites, PfCoronin is expressed late in the asexual lifecycle and localizes to the pellicle region of invasive merozoites before and during erythrocyte entry. PfCoronin also associates strongly with membranes within the cell, likely mediated by interactions with phosphatidylinositol-4,5-bisphosphate (PI(4,5)P-2) at the plasma membrane. Conclusions: These data suggest PfCoronin may fulfil a key role as the critical determinant of actin filament organization in the Plasmodium cell. This raises the possibility that macro-molecular organization of actin mediates directional motility in gliding parasites.

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