earticle

영어

Eukaryotic cells have evolved a N-glycan-dependent endoplasmic reticulum -mediated glycoprotein quality control (ER-QC) system. The ER-QC facilitates folding and modification of secretory and membrane proteins and eliminates terminally misfolded glycoproteins through ER-associated degradation (1). UDP-glucose: glycoprotein glucosyltransferase (UGGT), a key player in ER-QC, selectively reglucosylates misfolded glycoproteins for binding to CNX or CRT lectin/chaperones (2). The human pathogenic yeast Cryptococcus neoformans has unique N-linked glycosylation pathway, in which the mature precursor N-oligosaccharides without glucose residues are linked to asparagine on proteins (3). To investigate the physiological importance of ER-QC in C. neoformans, we constructed a mutant strain lacking UGGT by deleting the gene encoding UGGT. Notably, the C. neoformans uggtΔ stain showed a delayed growth rate even at normal growth condition and severe growth defects under several stress conditions, including high temperature, ER stress, and cell wall stress. Furthermore, the C. neoformans uggtΔ strain displayed defect in the capsule formation and the melanin biosynthesis, which are representative virulence-associated factors. Our results demonstrated that the UGGT-mediated ER-QC system plays a significant role in stress resistance, virulence, and even normal cell growth of Cryptococcus neoformans.