Protein O-fucosylation in Plasmodium falciparum ensures efficient infection of mosquito and vertebrate hosts

Sash Lopaticki, Annie S. P. Yang, Alan John, Nichollas E. Scott, James P. Lingford, Matthew T. O’Neill, Sara M. Erickson, Nicole C. McKenzie, Charlie Jennison, Lachlan W. Whitehead, Donna N. Douglas, Norman M. Kneteman, Ethan D. Goddard-Borger () and Justin A. Boddey ()
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Sash Lopaticki: The Walter and Eliza Hall Institute of Medical Research
Annie S. P. Yang: The Walter and Eliza Hall Institute of Medical Research
Alan John: The Walter and Eliza Hall Institute of Medical Research
Nichollas E. Scott: University of Melbourne at the Peter Doherty Institute for Infection and Immunity
James P. Lingford: The Walter and Eliza Hall Institute of Medical Research
Matthew T. O’Neill: The Walter and Eliza Hall Institute of Medical Research
Sara M. Erickson: The Walter and Eliza Hall Institute of Medical Research
Nicole C. McKenzie: The Walter and Eliza Hall Institute of Medical Research
Charlie Jennison: The Walter and Eliza Hall Institute of Medical Research
Lachlan W. Whitehead: The Walter and Eliza Hall Institute of Medical Research
Donna N. Douglas: University of Alberta
Norman M. Kneteman: University of Alberta
Ethan D. Goddard-Borger: The Walter and Eliza Hall Institute of Medical Research
Justin A. Boddey: The Walter and Eliza Hall Institute of Medical Research

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: Abstract O-glycosylation of the Plasmodium sporozoite surface proteins CSP and TRAP was recently identified, but the role of this modification in the parasite life cycle and its relevance to vaccine design remain unclear. Here, we identify the Plasmodium protein O-fucosyltransferase (POFUT2) responsible for O-glycosylating CSP and TRAP. Genetic disruption of POFUT2 in Plasmodium falciparum results in ookinetes that are attenuated for colonizing the mosquito midgut, an essential step in malaria transmission. Some POFUT2-deficient parasites mature into salivary gland sporozoites although they are impaired for gliding motility, cell traversal, hepatocyte invasion, and production of exoerythrocytic forms in humanized chimeric liver mice. These defects can be attributed to destabilization and incorrect trafficking of proteins bearing thrombospondin repeats (TSRs). Therefore, POFUT2 plays a similar role in malaria parasites to that in metazoans: it ensures the trafficking of Plasmodium TSR proteins as part of a non-canonical glycosylation-dependent endoplasmic reticulum protein quality control mechanism.

Date: 2017
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DOI: 10.1038/s41467-017-00571-y

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