Protein O-fucosylation in Plasmodium falciparum ensures efficient infection of mosquito and vertebrate hosts
Details
Publication Year 2017-09-15, Volume 8, Issue #1, Page 561
Journal Title
Nature Communications
Publication Type
Journal Article
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.The role of O-glycosylation in the malaria life cycle is largely unknown. Here, the authors identify a Plasmodium protein O-fucosyltransferase and show that it is important for normal trafficking of a subset of surface proteins, particularly CSP and TRAP, and efficient infection of mosquito and vertebrate hosts.
Publisher
Springer Nature
WEHI Research Division(s)
Chemical Biology; Systems Biology And Personalised Medicine; Infection And Immunity
PubMed ID
28916755
Open Access at Publisher's Site
http://www.nature.com/articles/s41467-017-00571-y
NHMRC Grants
NHMRC/1049811 NHMRC/1100164 NHMRC/1037373
ARC Grants
ARC/DP110105395,
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2017-09-18 11:59:39
Last Modified: 2017-09-18 12:16:37
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