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Pmt介导的O-甘露糖基化作用可稳定白色念珠菌分泌装置的一种重要组分Sec20p。

Pmt-mediated O mannosylation stabilizes an essential component of the secretory apparatus, Sec20p, in Candida albicans.

作者信息

Weber Yvonne, Prill Stephan K-H, Ernst Joachim F

机构信息

Institut für Mikrobiologie Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1/Geb. 26.12, D-40225 Düsseldorf, Germany.

出版信息

Eukaryot Cell. 2004 Oct;3(5):1164-8. doi: 10.1128/EC.3.5.1164-1168.2004.

Abstract

Sec20p is an essential endoplasmic reticulum (ER) membrane protein in yeasts, functioning as a tSNARE component in retrograde vesicle traffic. We show that Sec20p in the human fungal pathogen Candida albicans is extensively O mannosylated by protein mannosyltransferases (Pmt proteins). Surprisingly, Sec20p occurs at wild-type levels in a pmt6 mutant but at very low levels in pmt1 and pmt4 mutants and also after replacement of specific Ser/Thr residues in the lumenal domain of Sec20p. Pulse-chase experiments revealed rapid degradation of unmodified Sec20p (38.6 kDa) following its biosynthesis, while the stable O-glycosylated form (50 kDa) was not formed in a pmt1 mutant. These results suggest a novel function of O mannosylation in eukaryotes, in that modification by specific Pmt proteins will prevent degradation of ER-resident membrane proteins via ER-associated degradation or a proteasome-independent pathway.

摘要

Sec20p是酵母中一种必需的内质网(ER)膜蛋白,在逆行囊泡运输中作为tSNARE组分发挥作用。我们发现,人类真菌病原体白色念珠菌中的Sec20p被蛋白质甘露糖基转移酶(Pmt蛋白)广泛O-甘露糖基化。令人惊讶的是,Sec20p在pmt6突变体中以野生型水平存在,但在pmt1和pmt4突变体中水平极低,并且在Sec20p腔结构域中的特定丝氨酸/苏氨酸残基被替换后也是如此。脉冲追踪实验表明,未修饰的Sec20p(38.6 kDa)在生物合成后迅速降解,而稳定的O-糖基化形式(50 kDa)在pmt1突变体中未形成。这些结果表明O-甘露糖基化在真核生物中有新功能,即特定Pmt蛋白的修饰将通过内质网相关降解或蛋白酶体非依赖途径防止内质网驻留膜蛋白降解。

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