Identification of essential exported Plasmodium falciparum protein kinases in malaria-infected red blood cells

Siddiqui, Ghizal, Proellochs, Nicholas I., and Cooke, Brian M. (2020) Identification of essential exported Plasmodium falciparum protein kinases in malaria-infected red blood cells. British Journal of Haematology, 188 (5). pp. 774-783.

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Abstract

FIKK kinases in the human malaria parasite Plasmodium falciparum are attractive targets for new anti-malaria drugs, as they have no orthologues in humans and have been linked to disease severity. Six FIKKs are known to be exported into red blood cells (RBCs) where they mediate dramatic structural and functional changes to RBCs that are central to pathogenesis. Eleven members of this family, which are predicted to be exported into infected RBCs (iRBCs), remain uncharacterised. Using a targeted gene-knockout approach, we have characterised these FIKKs and discovered that five are essential for parasite survival. Three of these five FIKKs (FIKK9.1, FIKK10.1, FIKK10.2) were exported from the parasite into iRBCs and for two of these (FIKK9.1 and FIKK10.1), export was via Maurer's clefts (parasite-derived structures involved in protein trafficking and pathognomonic of falciparum malaria). Of the remaining two essential kinases, FIKK3 was associated with rhoptries (specialised protein secretory organelles in the parasite) and FIKK9.5 was localised in the parasite nucleus. The diverse localisation and essentiality of these FIKKs demonstrate that they play different but essential roles in the survival of P. falciparum in RBCs and therefore are attractive new drug targets for the prevention or treatment of falciparum malaria.

Item ID: 60931
Item Type: Article (Research - C1)
ISSN: 1365-2141
Keywords: malaria, red blood cells, Plasmodium falciparum, kinases, FIKK kinases, drug targets
Copyright Information: © 2019 British Society for Haematology and John Wiley & Sons Ltd
Funders: European Union (EU)
Projects and Grants: EU Horizon 2020 Research and Innovation Programme. Grant Number: 790085.c
Date Deposited: 13 Nov 2019 07:39
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1102 Cardiovascular Medicine and Haematology > 110202 Haematology @ 100%
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