Pmt-mediated O mannosylation stabilizes an essential component of the secretory apparatus, Sec20p, in Candida albicans.
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.
Weber
Yvonne
Y
Institut für Mikrobiologie Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1/Geb. 26.12, D-40225 Düsseldorf, Germany.
Prill
Stephan K-H
SK
Ernst
Joachim F
JF
D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D002176:Candida albicans / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D005800:Genes, Fungal; D006031:Glycosylation; D006801:Humans; D008358:Mannose / Q000378:metabolism; D008364:Mannosyltransferases / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D025801:Ubiquitin / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
D005656:Fungal Proteins; D008562:Membrane Glycoproteins; D025801:Ubiquitin; D033921:Vesicular Transport Proteins; D008364:Mannosyltransferases; C082696:protein O-mannosyltransferase; D008358:Mannose