The nucleocytosolic O-fucosyltransferase SPINDLY affects protein expression and virulence in Toxoplasma gondii

نویسندگان

چکیده

Once considered unusual, nucleocytoplasmic glycosylation is now recognized as a conserved feature of eukaryotes. While in animals, O-GlcNAc transferase (OGT) modifies thousands intracellular proteins, the human pathogen Toxoplasma gondii transfers different sugar, fucose, to proteins involved transcription, mRNA processing, and signaling. Knockout experiments showed that TgSPY, an ortholog plant SPINDLY paralog host OGT, required for nuclear O-fucosylation. Here we verify TgSPY O-fucosyltransferase (OFT) by 1) complementation with TgSPY-MYC3, 2) its functional dependence on amino acids critical OGT activity, 3) ability O-fucosylate itself model substrate specifically hydrolyze GDP-Fuc. many endogenous modified O-Fuc are important tachyzoite fitness, O-fucosylation not essential. Growth ?spy tachyzoites fibroblasts modestly affected, despite marked reductions levels ectopically expressed normally O-fucose. Intact TgSPY-MYC3 localizes nucleus cytoplasm, whereas catalytic mutants often displayed reduced abundance. luciferase-expressing type II strain exhibited infection kinetics mice similar wild-type but increased persistence chronic brain phase, potentially due imbalance regulatory protein levels. The modest changes parasite fitness in vitro mice, profound effects reporter accumulation, characteristic punctate localization O-fucosylated suggest controls be held reserve response novel stresses.

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ژورنال

عنوان ژورنال: Journal of Biological Chemistry

سال: 2021

ISSN: ['1083-351X', '0021-9258', '1067-8816']

DOI: https://doi.org/10.1074/jbc.ra120.015883