TY  - JOUR
AU  - Lopaticki, S
AU  - Yang, ASP
AU  - John, A
AU  - Scott, NE
AU  - Lingford, JP
AU  - O'Neill, MT
AU  - Erickson, SM
AU  - McKenzie, NC
AU  - Jennison, C
AU  - Whitehead, LW
AU  - Douglas, DN
AU  - Kneteman, NM
AU  - Goddard-Borger, ED
AU  - Boddey, JA
Y2  - 2020/12/21
Y1  - 2017/09/15
SN  - 2041-1723
UR  - http://hdl.handle.net/11343/257012
AB  - 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.
LA  - English
PB  - NATURE PUBLISHING GROUP
T1  - Protein O-fucosylation in Plasmodium falciparum ensures efficient infection of mosquito and vertebrate hosts
DO  - 10.1038/s41467-017-00571-y
IS  - Nature Communications
VL  - 8
IS  - 1
L1  - /bitstream/handle/11343/257012/PMC5601480.pdf?sequence=1&isAllowed=y
ER  -